TW509687B - Novel piperazine derivatives having combined 5HT1A, 5HT1B and 5HT1D recept or antagonist activity and their use for the treatment and prophylaxis of various CNS disorders - Google Patents

Novel piperazine derivatives having combined 5HT1A, 5HT1B and 5HT1D recept or antagonist activity and their use for the treatment and prophylaxis of various CNS disorders Download PDF

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TW509687B
TW509687B TW087105843A TW87105843A TW509687B TW 509687 B TW509687 B TW 509687B TW 087105843 A TW087105843 A TW 087105843A TW 87105843 A TW87105843 A TW 87105843A TW 509687 B TW509687 B TW 509687B
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indole
dihydro
small
methyl
phenylaminocarbonyl
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Laramie Mary Gaster
Harshad Kantilal Rami
Paul Adrian Wyman
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Smithkline Beecham Plc
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    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract

Compounds of formula (I), processes for their preparation and their use as CNS agents are disclosed: in which Ra is a group of formula (i), in which P1 is phenyl, naphthyl, quinolinyl, or tetrahydroisoquinolinyl; R1 and R2 are independently hydrogen, halogen, C1-6alkyl, cyano, C1-6alkoxy-carbonylamino; a is 1 or 2; or Ra is a group of formula (ii) wherein P2 and P3 are independently phenyl, naphthyl, thienyl, furyl, imidazolyl, oxazolyl, pyrazolyl, thiazolyl, oxadiazolyl, pyrimidyl, pyridazinyl, pyrazinyl, pyridyl, piperidinyl, quinolinyl, isoquinolmyl, or tetrahydroisoquinolinyl; A is a bond or oxygen, -CH2-CH2-, or NR4 where R4 is hydrogen or C1-6alkyl; R1, R2, R3 are independently hydrogen, halogen, C1-6alkyl, C1-6alkanoyl, or cyano; Y is -NH- or -CH2-; W is -CH=CH- or -(CH2)t-, where t is 2 or 3; Rb is hydrogen, halogen, C1-6alkyl, trifluoromethyl, C1-6alkoxy, or C2-6alkenyl; Rc is hydrogen or C1-6alkyl.

Description

1 本發明相闕於新穎穴氫此讲衍生物，其製備方法，以 及包含彼等之醫藥組合物。 ， wo 循6637、) 95/0<5〇44 及 w〇 95/〇4729 揭示一 系雛有SHUif拮蝴雜之六細畊衍生物。此等 化合物經陳述具有治療各式CNS病症，例如抑#症之用 迷。EPA0533266/7/8揭示-系列具有541Tid受體拮抗劑活 性之苯甲醯胺苯衍生物。 從化合物結構上不同類別，現已發現可產生組合 ’ΗΤιΑ、5ΗΤιΒ及5HT1D3體拮抗劑活性。並預期該等化合 物相當迅速的開始作用將會有用於治療及預防各式CNS病 症。因此，在最初方面本發明提供一種具式⑴化合物或其 鹽類： ，1 The present invention is related to novel anhydroxan derivatives, their preparation methods, and pharmaceutical compositions containing them. , Wo follow 6637,) 95/0 < 5040 and 〇95 / 〇4729 revealed that a series of six fine-cultivated derivatives of SHUif antagonists. These compounds have been stated to be useful in the treatment of various CNS disorders, such as diarrhea. EPA0533266 / 7/8 discloses a series of benzamidine benzene derivatives having 541Tid receptor antagonist activity. From different classes of compound structures, it has now been found to produce combined ′ ΗΤιΑ, 5ΗΤιΒ and 5HT1D3 somatic antagonist activity. It is expected that the relatively rapid onset of these compounds will be useful in the treatment and prevention of various types of CNS diseases. Therefore, in an initial aspect, the present invention provides a compound of formula (I) or a salt thereof:

經濟部中央標準局員工消費合作社印製 其中1^為具式⑴之一群Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

其中P為苯基、雙環芳基、含有1至3個選自氧、氮和硫 雜原子之5至7員雜環、或含有1至3個選自氧、氮和硫雜 原子之雙環雜環； 本紙張尺度適用( CNS ( 210^^7 509687 A7 ___B7五、發明説明（2 ) R1為氫、鹵素、Ci-6烷基、C3«6環烷基、COCk烷基、Cw 燒氧基、經基、經基Cue烧基、羥基Ck烧氧基；Ci»6燒氧 基Ck院氧基、Ck烧醇基、硝基、三氟甲基、氰基、SR9、 SOR9、S02R9、SCbNI^R11、C02R1G、CONR1GRn、 C02NR,()R11 ^ CONRl0(CH2)cCO2Rn ^ (CH2)cNR10Ru > (CH2)eCONRK’Rn、(CH2)cNR1GC0Rn .、(CH2)cC02Cw 烷基、 C02(CH2)c0Ru>、NR1GR"、NRH)C02R"、NRu)CONR“)Ru、 CRi()=NORu、NR^COOR11、CNRK)=NORn，其中 R10 和 R"獨立為氫或Ck烷基，且c為1至4 ; 為氫、鹵素、Ci«6院基、C3«6環烧基、C3-6環稀基、Ci-6 烧氧基、Ci-6说醇基、芳基、酸氣基、經基、硝基、三氟甲 基、氰基、C02R1G、COiNTt10Rn、NR1()RU，'其中 R10 和 R11 係如R1所定義·； a為1、2或3 ; 或Ra4具式⑻之一群Wherein P is a phenyl group, a bicyclic aryl group, a 5- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur, or a bicyclic heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur Ring; This paper is suitable for size (CNS (210 ^^ 7 509687 A7 ___B7 V. Description of the invention (2) R1 is hydrogen, halogen, Ci-6 alkyl, C3 «6 cycloalkyl, COCk alkyl, Cw alkoxy , Mesyl, mesyl Cue, hydroxy Ck, oxy; Ci »6 alkoxy, Ck, oxy, Ck, alkoxy, nitro, trifluoromethyl, cyano, SR9, SOR9, S02R9, SCbNI ^ R11, C02R1G, CONR1GRn, C02NR, () R11 ^ CONRl0 (CH2) cCO2Rn ^ (CH2) cNR10Ru > (CH2) eCONRK'Rn, (CH2) cNR1GC0Rn., (CH2) cC02Cw alkyl, C02 (CH2) 0 ;, NR1GR ", NRH) C02R ", NRu) CONR ") Ru, CRi () = NORu, NR ^ COOR11, CNRK) = NORn, where R10 and R " are independently hydrogen or Ck alkyl, and c is 1 to 4; for hydrogen, halogen, Ci «6 courtyard, C3« 6 ring alkyl, C3-6 ring dilute group, Ci-6 alkyloxy group, Ci-6 alcohol group, aryl group, acid gas group, warp group , Nitro, trifluoromethyl, cyano, C02R1G, COiNTt10Rn, NR1 () RU, where R10 and R11 are as R As defined by 1; a is 1, 2 or 3; or a group of Ra4

經濟部中央標準局員工消費合作社印製 其中P2和P3獨立為苯基、雙環芳基、含有1至3個選自氧、 氮和硫雜原子之5至7員雜環、或含有1至3涵選自氧、氮 或硫雜原子之雙環基E; A為鍵或氧、S(0)m其中m為0至2、羰基、CH2、-CH2-CH2_、 或NR4，其中R4為氫或Cw烷基； R1係如上式①所定義，或Rl為含有1至3個選自氧、氮或 ___4 本紙張尺度適用中國國家樣準（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs where P2 and P3 are independently phenyl, bicyclic aryl, containing 1 to 3 heterocyclic rings of 5 to 7 members selected from oxygen, nitrogen and sulfur heteroatoms, or containing 1 to 3 It is selected from the group consisting of a bicyclic group E of oxygen, nitrogen or sulfur heteroatom; A is a bond or oxygen, S (0) m where m is 0 to 2, carbonyl, CH2, -CH2-CH2_, or NR4, where R4 is hydrogen or Cw alkyl; R1 is as defined in formula ① above, or Rl contains 1 to 3 selected from oxygen, nitrogen or ___4 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Please read first (Notes on the back then fill out this page)

509687 A7 B7 —一 —— ________________ 五、發明説明（） 3 硫雜原子之5至7員雜環，視需要可經Cw烷基、滷素、 Cw烷酵基所取代； R2和R3獨立為氫、卤素、Cu6烷基、Cw環烷基、Cw環烯 基、ew烷氧基、Cm烷酵基、芳基、醯氧基、羥基、硝基、 三氟甲基、氰基、C02R10、CONRWR11、NR10Rn，其中 yo 和R11係如R1所定義； 且a和b猶立為0、1、2或3 ; Y為-NH·、-NR5-，其中R5為Cw烷基，或Ϋ為·CHr或 V為氧或硫； D為氮、碳或CH基；W為(CR16R17)t，其中t為2、3或4 且R16和R17獨立為氫或Cle6烷基或W為(CR16R17VJ，其中 u 為 0、1、2 或 3 且 J 為氧、硫、CR16=CR17、CR16;N、N：R160、 =CR16S 或=CR16-NR17 ; X為氮或碳；509687 A7 B7 —One—— ________________ V. Description of the invention (5) 5 to 7-membered heterocyclic ring of sulfur heteroatom, which can be replaced by Cw alkyl, halogen, and Cw alkanoyl if necessary; R2 and R3 are independently hydrogen, Halogen, Cu6 alkyl, Cw cycloalkyl, Cw cycloalkenyl, ew alkoxy, Cm alkanoyl, aryl, fluorenyl, hydroxy, nitro, trifluoromethyl, cyano, C02R10, CONRWR11, NR10Rn, where yo and R11 are as defined by R1; and a and b are 0, 1, 2 or 3; Y is -NH ·, -NR5-, where R5 is Cw alkyl, or Ϋ is · CHr or V is oxygen or sulfur; D is nitrogen, carbon or CH group; W is (CR16R17) t, where t is 2, 3 or 4 and R16 and R17 are independently hydrogen or Cle6 alkyl or W is (CR16R17VJ, where u is 0, 1, 2 or 3 and J is oxygen, sulfur, CR16 = CR17, CR16; N, N: R160, = CR16S or = CR16-NR17; X is nitrogen or carbon;

Rb為氫、鹵素、羥基、Cm烷基、三氟甲基、Cm烷氧基、 Cw烯塞、視需要經烷基所取代之C3-7環烷基、或芳基； 圮為氫或Cm烷基；且 當X為氮時，=為單鍵，或當X為碳時，其為單戚雙鍵。 經濟部中央標準局員工消費合作社印製 單獨或另外基®—部份之Cle6烷基係可為直鏈或支 鏈。文中所使用術語“醯氧基”係指_〇〇(〇)(：^6烷基0文t 所使用來敘逮之術語“芳基”，除非另有說明，德指基® 如苯基。文中所使用來敘述之術語‘‘芳烷基”，除非另有 陳述，係指基圈如芊基〇 由可部份飽和之P1、P2及/或P3所代表之雙環芳基，較 本紙張尺度適用中國國家標準（CNS ) A4規格（210X^97公釐) A7 s-----E 五、發明説明（4 ) 經濟部中央標準局員工消費合作社印製 佳為蔡基9 含有1至3個選自氧、氮和硫雜原子之雙環雜環實例包 括異邊淋、吲哚、苯并呋喃〗苯并碟吩，且較佳為喹琳。 由P1、P2及/或P3所代表含有1至3個選自氧、氮和硫 雜原子之$至7員雜環實例包括礞吩基、呋喃基、吡咯基、 二峻基、_禮基、喝咬基、壤竣基、0f二座基、異雀魂基、 異0f峰基、碟二峻基、癌咬基、塔讲基和此讲基，且較佳 為此咬基。 如上所述之雜環，可經由碳原子或，當存在有適合的 氮原子時’被鍵聯至分子其餘部份。該等環亦可為飽和或 部份飽和。飽和或部份飽和之5至7員雜環實例包括六氫此 畊' 略啶和嗎啉。部份飽和之雙環雜環實例包括二氫苯 并呋喃、二氮笨并噻吩、四氫喹淋和四氮異喹琳。 R1較佳為南素原子，例如氟、氣或溴，且R2及/或R3 各自較隹為氫、由素，例如氣基、或Ci-6燒基，例如甲基。 常R1為5至7員雜環時，合適之視需要取代基包括<^_6烷 基、Cl-6燒醇基和齒素。 a和b各自較佳為1或2。 A較佳為鍵或氧，最佳為鍵c» Y敉佳為-NH-。 V較佳為氧。 D較隹為氮且W基観較隹為(CRi6R17)t基，其中R16和R17 各自有利為氩，且t適合為2。 Rb較佳為氫或由素原子，例如氣、Ck烷氧基，例如甲氧基 本紙張尺度適用中國國家標準（CNS ) A4規格（210'〆297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 509687 Α7 Β7 五、發明説明（5 ) 或Ck烷基’例如甲基或乙基· X較佳為氮βRb is hydrogen, halogen, hydroxy, Cm alkyl, trifluoromethyl, Cm alkoxy, Cw alkenyl, C3-7 cycloalkyl, or aryl substituted with alkyl if necessary; 圮 is hydrogen or Cm Alkyl; and when X is nitrogen, = is a single bond, or when X is carbon, it is a single double bond. Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. Alone or other radicals-part of the Cle6 alkyl system can be straight or branched. As used herein, the term "fluorenyloxy" refers to _〇〇 (〇) (: ^ 6alkyl0. The term "aryl" is used to describe the term, unless otherwise specified, German refers to a group such as phenyl The term "aralkyl" used in the text, unless otherwise stated, refers to a base ring such as fluorenyl group. Bicyclic aryl group represented by partially saturable P1, P2 and / or P3. Paper size applies Chinese National Standard (CNS) A4 specification (210X ^ 97 mm) A7 s ----- E V. Description of invention (4) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs as Cai Ji 9 Contains 1 Examples of three bicyclic heterocycles selected from the group consisting of oxygen, nitrogen and sulfur heteroatoms include isoprenaline, indole, benzofuran, benzophenone, and preferably quinine. P1, P2 and / or P3 Examples of $ to 7-membered heterocyclic rings containing 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur heteroatoms include fluorenyl, furyl, pyrrolyl, dibenzyl, ceryl, nicotyl, terpine, 0f two bases, isosophyl radicals, iso 0f peak bases, disc two bases, cancer bite bases, tower bases and this bases, and preferably these bases. As mentioned above, heterocycles can be passed through carbon Atomic or When there is a suitable nitrogen atom, 'is bonded to the rest of the molecule. These rings can also be saturated or partially saturated. Examples of saturated or partially saturated 5 to 7 membered heterocyclic rings include hexahydrogen " Leptidinium and morpholine. Examples of partially saturated bicyclic heterocyclic rings include dihydrobenzofuran, diazabenzothiophene, tetrahydroquinine, and tetraazaisoquineline. R1 is preferably a southern atom such as fluorine, gas, etc. Or bromine, and each of R2 and / or R3 is more hydrogen than fluorene, such as a gas group, or a Ci-6 alkyl group, such as a methyl group. When R1 is a 5 to 7-membered heterocyclic ring, a suitable substituent as necessary Including < ^-6 alkyl, Cl-6 alcohol group and tooth element. A and b are each preferably 1 or 2. A is preferably a bond or oxygen, most preferably a bond c »Y is preferably -NH- V is preferably oxygen. D is more nitrogen than W and W is more than (CRi6R17) t group, wherein R16 and R17 are each preferably argon, and t is suitably 2. Rb is preferably hydrogen or a prime atom, Such as gas, Ck alkoxy, such as methoxy This paper size is applicable to Chinese National Standard (CNS) A4 specifications (210'〆297 mm) (Please read the precautions on the back before filling this page) Order 509687 Α7 Β7 V. hair Description (5) alkyl or Ck 'example methyl or ethyl preferably nitrogen β · X

Rc較佳為Ck燒基，例如甲基。 根據本發明，特別較佳化合物係包括： H(4_漠_3_甲笨基)胺基羰基】·5_甲氧基各(参甲基六氫吡讲_ 1-基)-1Η4| 哚， H(4_淡各甲笨基)胺基羰基】·23_二氫-5-甲氧基4(4-甲基 六氫畎讲-1_基, H(2>二氣苯基)胺基羰基】_23_二氫·5·甲氧基各(4·甲基六 氫此讲-1-基嗓， 2,3_二氫-5-甲氧基.6.(4.甲基六氫此讲小基)小f4_(毗啶冰 基)萘-1基胺基羰基]_1好_吲哚， f 2,3·二氫-5-甲氧基-心(4_甲基六氫此讲· ^基)小[5七tt啶冰 基)萘_1基胺基羰基】·1Η-吲哚， Η(2,3-二氣-4_(吡啶+基)苯基胺基羰基】-2,3-二氫·5_甲氧 基_6_(4-甲基六氫此讲-^基^挪吲哚， 2,3-一氫_5·甲氡基_6-(4-甲基六氮此_+基)小(邊秦5-基胺 基幾基}丨味， 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 2,3_二氫_6 士^甲基大氫吡蟒+基)(毗啶冰基)蓽+基 胺基幾基)-1Η·^5丨啼， 氣·2,3·二氫_6_(4"甲基六氫吡蟒·ι_基Η·[4_(4啶斗基)萘-1-基胺基羰基)-1中吲哚， 5-溪4,3-二氫4(‘甲基六氫此讲+基)4朴(说咬冰基漆 1-基胺基羰基吲哚， 7Rc is preferably Ck alkyl, such as methyl. According to the present invention, particularly preferred compounds include: H (4-mo_3_methylbenzyl) aminocarbonyl] · 5-methoxy ((p-methylhexahydropyridin-1-yl) -1Η4 | Indole, H (4-methylaminobenzyl) aminocarbonyl] · 23_dihydro-5-methoxy4 (4-methylhexahydrofluorenyl-1-yl, H (2 > diphenylphenyl) ) Aminocarbonyl group] _23_dihydro · 5 · methoxy each (4 · methylhexahydro this talk-1-yl group, 2,3_dihydro-5-methoxy group. 6. (4. 甲Hexahydro, small group) small f4_ (pyridinyl) naphthalene-1ylaminocarbonyl group] _1good_indole, f 2,3 · dihydro-5-methoxy-heart (4-methyl Hexahydro this ^ group) small [5 heptidine ice group) naphthalene_1 ylaminocarbonyl] 1 Η-indole, Η (2,3-digas-4_ (pyridine + yl) phenylamino Carbonyl group] -2,3-dihydro · 5-methoxy-6- (4-methylhexahydro this talk- ^ yl ^ indole, 2,3-monohydro-5 · methylfluorenyl-6- ( 4-methylhexazine this _ + group) small (5-Qinyl amino group of Bentham Qin) 丨 taste, printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 2 , 3_dihydro_6 甲基 methyl bighydropyrazine + yl) (pyrimidinyl) fluorene + amine amino group -1 Η 5 ^ cry, gas 2,3, dihydro_6_ (4 " methyl Hydropyridine · ι_ylΗ · [4- (4-pyridinyl) naphthalene-1-ylaminocarbonyl) -1 indole, 5-brook 4,3-dihydro 4 ('methylhexahydro + Radical) 4 pak (say bite ice-based lacquer 1-ylaminocarbonylindole, 7

509687 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（6 ) 5-溴-2,3-二氫-6-(4_f基六氫毗讲小基)小[4_(嘁啶斗基)苯 基胺基羰基}-m-嗍哚， 5_溴-1-[3-氣冰(此啶-4-基)笨棊胺基羰基】·2,3-二氫-6-(冬甲 基六氫基)-1Η-吲哚， 2.3- 二氮-5:甲基·6_(4-甲基六氮此讲·1·基)_1，[4-(此咬《4-基) 萘-1-基胺基幾基】-1Η-吲哚， 1-[3_氣-4-(4b啶4·基)苯基胺基羰基】-2,3-二氫-5-甲基-6-(4-甲基六氫此讲4-基)-1Η-吲哚， 2.3- 二氧甲基六氮讲-1-基)-1-[4«(赴咬-Φ*基)祭，1，基 胺基羰基】-5-乙烯基-1Η-吲哚， 2.3- 二氮_5-己基-6-(4_甲基六氮讲‘1-基)-1_[4_(此咬-4_基) 萘-1-基胺基羰基】-1H-吲哚， · 1 -[3 -氣-4-(4b咬-4·基)苯基胺基魏基]_2,3_二氮-5-乙基-6-(4-甲基六氫此讲-l-基嘴， 2,3_二氮·6_(4-甲基六氮此讲_1·基)-1-[4-(此唆_4-基)祭-1-基 胺基羰基】-5-三氟甲基-1Η_吲哚， 氣_4_(此唆-4-基)苯基胺基魏基]-2,3-二氮*6-(4-甲基六 氮讲-1-基)-5-三氣甲基-IH-S丨樣’ 2.3- 二氮-5-甲氧基-6-(4-甲基六氮此讲-1-基)*1^[4-(此咬·4· 基)萘基乙醯基ΗΗ-吲哚， 2.3- 二氮-5-甲氧基-6_(4-甲基六氮《14讲_1-基) 基)-萘基乙醯基】_lfr吲哚， 2,3*二氮-6-(4-甲基六氮4b讲-基)_1-[4-(赴唆，4_基)奈·1-基 乙醯蓦]4H-嘧哚， 8 (請先閲讀背面之注意事項再填寫本頁) t ---- ----— . ____________ ; ..... .......... ... . . ____ . ' 1 , 本紙張尺度適用中國國家標準（CNS ) A4規格（210Χ297公釐） 509687 A7 B7 五、發明説明（7 ) 5-氣-2,3-二氮-6-(4-甲基六氮 4b 讲-1-基)-1·[Φ*(〇Λ 唆 *4-基)茶· 1-基乙醯基】-1Η·吲#， 5_>臭-2,3-二氮-6_(4·甲基六氮你讲_1·基)·1-[4-(〇Λ唆-4-基)蔡_ 1-基乙醯基】-1Η-吲#， 2,3·二氮_6‘(4_甲基六氮此讲_1_基)-1-[4-(此咬，4-基)祭·1-基 乙釀基】_5-乙稀基卜朵’ 5-漠·_2,3*·二氮“6-(1·甲基六氮此讲-4-基)-1胃[4~(赴咬—4-基)餐· 1-基胺基羰基]·1Η-吲哚， 5-氣-2,3_ 二氮-6_(4-甲基六氮 〇tb 讲-1-基)-l-[5-(4b 唆-4-基)蔡· 1-基胺基羰基]4H-吲哚， 5- 演-2,3-二氮-6-(4·甲基六氮〇tt讲-1·基)·1-[5-(此咬-4-基)蔡· 1-基胺基羰基]4Η-吲哚， · 2.3- 二氮_5_甲氧基-6-(4-甲基六氮此讲-1-基)-1-(峻淋-6“基胺 基羰基)-1Η-吲哚， 2.3- 二氫+[4_(第三-丁氧基羰基胺基)苯基胺基羰基]-5-氣· 6- (4·甲基六氫4b畊吲哚， 5- 澳-2,3_二氮-6-(4-甲基六氮〇tb讲-1-基)_1-(者琳-6_基胺基魏 基)-1Η，吲哚， 經濟部中央標準局員工消費合作社印製 6- 溴-7-(4-甲基六氫吡讲-1·基)4_[4七比啶-4-基)萘-1-基胺基 羰基Η，2,3,4,四氫喹郝， 5·氣*2,3-二氣各(4-甲基六氫此讲-1·基)_1·(4·笨氧基苯基胺 基羰棊)-1Η-吲唓， 5-氣-2,3.二氫氣笨氧基)笨基胺基羰基)各(4-甲基六 氫吡4_1_基)-1Η-吲哚， 9 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐) 經濟部中央標準局員工消費合作社印製 509687 A7 ___B7 五、發明説明（8 ) 5-氣-2,3-二氫τ6-(4_甲基六氫吡畊士基)^喹淋·6_基胺基羰 基)-1Η-吲哚， 5-氣_2,3-二氫-6-(4-甲基六氫蚱讲小基>1_(3_苯氧基苯基胺 基羰基)_1ΗΗ丨嗓★ 5-氣-2,3-二氫-6-(4-甲基六氳吡讲_ι_基)_μ[4-(嘴咬-2·基)苯 基胺基羰基】-1Η.吲哚， 1-(3-+氧基苯基联基幾基)^5-氣_2,3-二氮*6_(4_甲基六氮此 讲4-基)·1Η-嗍哚， 1-(4-苄氧基苯基胺基羰基)·5-氣-2,3-二氮«4-甲基六氫吡 4- 1-基)_1Η-吲哚， 5- 氣-2,3-—^氮·6-(4•甲基六氮此讲·1_基)_ι·(2_甲基邊淋·6·基 胺基羰基)·1Η-吲哚， · 5-氣_2,3-二氫-1-[4七夫喃-2-基)苯基胺基羰基]各(4_甲基六 氮0Λ讲-1-基， 5,氣-2,3·二氫-6-(4-甲基六氫吡4-1_基)_1-【4七塞吩-2-基)苯 基胺基羧基]， 5-氣-2,3_二氫-6.(4-甲基六氫1此讲-1-基)_1-[5-(此咬-2·基)萘-1-基乙醯基】-1H-,嗓， 5‘>奐-2,3-二氣-6·(4-甲基六氫ϋ^ι#·1_基)小[5·(此务4-基)萘-1-基己釀基】啼， 5-氣_2,3_二氣士 [4<μ甲基六氩吡讲+基)萘4,基胺基鞔 基】-6·(4-甲基六氫说讲小基>lH_吲哚， 5-氣-2,3_二氫小【4“(2-甲基嘮唑_4·基)苯基胺基羰基]-6·(4· 甲基六氫吡蟒4_基)-111-吲哚， 10 百氏張尺度適用中國國( 2似29兩 (請先閲讀背面之注意事項再填寫本頁)509687 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention (6) Phenyl) phenylaminocarbonyl} -m-oxindole, 5-bromo-1- [3-air ice (this pyridin-4-yl) benzylaminocarbonyl]] 2,3-dihydro-6- ( Winter methyl hexahydro) -1Η-indole, 2.3-diaza-5: methyl 6- (4-methylhexaazine 1 · yl) _1, [4- (This bite "4-yl ) Naphthyl-1-ylamino] -1] -indole, 1- [3-Ga-4- (4bpyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-5-methyl -6- (4-methylhexahydro this 4-yl) -1 fluorene-indole, 2.3-dioxomethylhexaaza -1--1-yl) -1- [4 «(Go to the bite-Φ * group ), 1, aminoaminocarbonyl] -5-vinyl-1fluorene-indole, 2.3-diaza-5-hexyl-6- (4-methylhexazine speaking '1-yl) -1_ [4_ ( This bit-4-yl) naphthalene-1-ylaminocarbonyl] -1H-indole, · 1- [3-Ga-4- (4bbit-4-yl) phenylaminoweiyl] _2,3 _Diazine-5-ethyl-6- (4-methylhexahydro this talk-l-yl mouth, 2,3_diazine · 6_ (4-methylhexaazine this talk_1 · yl) -1 -[4- (This fluoren-4-yl) -1--1-aminoaminocarbonyl] -5-trifluoromethyl-1 fluorene-indole, 4-4- (this fluoren-4-yl) phenylamino ] -2,3-diazepine * 6- (4-methylhexazine-1-yl) -5-trifluoromethyl-IH-S 丨 like '2.3-diaza-5-methoxy-6 -(4-methylhexaaza-1--1-yl) * 1 ^ [4- (this bite · 4-yl) naphthylacetamidinium-indole, 2.3-diaza-5-methoxy- 6_ (4-Methylhexazine "Lecture 14_1-yl) -naphthylacetamido] _lfr indole, 2,3 * diazine-6- (4-methylhexaazine 4b lecture-yl) _1- [4- (Go to 唆, 4_ based) nai · 1-ylacetamidine] 4H-pyrimidine, 8 (Please read the notes on the back before filling this page) t ---- ---- —. ____________; ..... .......... ..... ____. '1, This paper size applies to China National Standard (CNS) A4 (210 × 297 mm) 509687 A7 B7 5 Description of the invention (7) 5-Gas-2,3-diazine-6- (4-methylhexaazine 4b 1-1-yl) -1 · [Φ * (〇Λ 唆 * 4-yl) tea · 1-ylethanyl] -1Η · ind #, 5_ > odor-2,3-diaza-6_ (4 · methylhexazine you speak _1 · yl) · 1- [4- (〇Λ 唆- 4-yl) Cai_ 1-ylethenyl] -1Η-indene #, 2,3 · diazine_6 '(4-methylhexaazine_1_yl) -1- [4- (this Bite, 4-based) offering · 1-based ethyl brewing group] _5-Ethyl alkoxy '5- Mo · _2,3 * · diazine "6- (1 · methylhexazine this 4--4-yl ) -1 stomach [4 ~ (Going to bite- 4-yl) meal · 1-Aminoaminocarbonyl] · 1-Indole, 5-Gas-2,3_diazine-6_ (4-methylhexazine 0tb) l- [5- (4b fluoren-4-yl) Cai · 1-ylaminocarbonyl] 4H-indole, 5-en-2,3-diazine-6- (4 · methylhexazine) -1 · yl) · 1- [5- (this bite-4-yl) Cai · 1-ylaminocarbonyl] 4Η-indole, 2.3-diaza-5_methoxy-6- (4- Methylhexaazine-1-yl) -1- (Junlin-6 "ylaminocarbonyl) -1Η-indole, 2.3-dihydro + [4- (third-butoxycarbonylamino) benzene Aminoaminocarbonyl] -5-Ga · 6- (4 · methylhexahydro 4b gindole, 5-o-2,3_diazine-6- (4-methylhexazine) ) _1- (Zhelin-6_ylaminoweiji) -1Η, indole, printed by 6-Bromo-7- (4-methylhexahydropyridine) Group) 4- [4Heptapyridin-4-yl) naphthalene-1-ylaminocarbonyl hydrazone, 2,3,4, tetrahydroquinoline, 5 · gas * 2,3-digas each (4-methyl Hexahydro--1 · yl) _1 · (4 · benzyloxyphenylaminocarbonyl hydrazone) -1Η-indole, 5-Gas-2,3.dihydrobenzyloxy) benzylaminocarbonyl) Each (4-methylhexahydropyridine 4_1_yl) -1Η-indole, 9 This paper size is applicable to China National Standard (CNS) A4 specifications (2 10X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 ___B7 V. Description of the invention (8) 5-Gas-2,3-dihydroτ6- (4-methylhexahydropyridinyl) ^ quine Lyn-6-aminoaminocarbonyl) -1Η-indole, 5-gas_2,3-dihydro-6- (4-methylhexahydro grasshopper small group> 1_ (3_phenoxyphenyl group) Aminocarbonyl) _1ΗΗ 丨 ΗΗ 5-Gas-2,3-dihydro-6- (4-methylhexamethylpyridinyl) _μ [4- (mouth bite-2.yl) phenylamine Carbonyl] -1 Η. Indole, 1- (3- + oxyphenylbienyl) ^ 5-gas_2,3-diazine * 6- (4-methylhexaazine 4-yl) · 1Η-indole, 1- (4-benzyloxyphenylaminocarbonyl) · 5-Gas-2,3-diazine «4-methylhexahydropyridine 4- 1-yl) _1Η-indole, 5-Gas-2,3-^ nitrogen 6- (4-methylhexazine this talk 1-yl) _ι · (2-methyl edge lye 6.ylaminocarbonyl) 1-indole , · 5-Gas_2,3-dihydro-1- [4-heptafur-2-yl) phenylaminocarbonyl] each (4-methylhexazine 0Λ-1--1-yl, 5, gas- 2,3 · dihydro-6- (4-methylhexahydropyridin-4-yl) _1- [4-heptaphen-2-yl) phenylaminocarboxyl], 5-gas-2,3_ Dihydro-6. (4-methylhexahydro-1 this talk-1-yl) _1- [5- (this bite-2 · yl) naphthalene-1-ylethylfluorenyl] -1H-, throat, 5 ' & g t; 奂 -2,3-digas-6 · (4-methylhexahydroϋ ^ ι # · 1_yl) small [5 · (this service 4-yl) naphthalene-1-ylhexyl]] , 5-Gas_2,3_Digas [4 < μmethylhexahydropyridine + yl) naphthalene 4, ylaminopyridyl] -6 · (4-methylhexahydroid small group> lH _Indole, 5-Gas-2,3_dihydro small [4 "(2-methyloxazol-4-yl) phenylaminocarbonyl] -6 · (4 · methylhexahydropyrazine 4_ Base) -111-indole, 10 hundredth Zhang scale applicable to China (2 like 29 two (please read the precautions on the back before filling this page)

、1T 509687 A7 B7 五、發明説明（9 ) 5-漠-2,3-二氮 **6·(4-甲基六氮 〇ffc 讲-1-基)-1-[4-(2·甲基 〇tfc 咬· 4- 基)苯基胺基-羰基】-1H-1?丨峰， 5_氣麵2,3騰二氮-6，(4-甲基六氧赴讲-1“基)《»1·[4·(2-甲基此咬馨 4*基)笨基胺基羰基Ϊ-1Η·吲哚， 5_氣-2,3·二氫·Η4-(2,6-工甲基此啶-4·基)苯基胺基羰基】各 (4·甲基六氮此讲-1-基)-ΙΗ-1?丨峰， 5_溴-2,3_二氫-1·[4·(2,6-二甲基吡咬冰基)苯基胺基羰基】_6-(4,甲基六氫毗讲4·基>1Η-吲哚， 2.3- 二氫-Η4_(2,6-二甲基吡啶_4·基)苯基胺基羰基]-5-甲氧 基_6-(4-甲基六氫毗4-1-基)-1Η-吲哚， 5- 氣-2,3.二氫-1-[4·(2,6·二甲基吡啶各基)苯基胺基羰基]各 (4-甲基六氫北基)4Η-,碌， f 5-溪-2,3-二氮_1-[4·(2,6-二甲基咬-3-基)苯基胺基幾基]-6-(4-甲基六氮此讲-1-基嗓， 2.3- 二氳小[4-(2,6-二甲基吡啶_3_基)苯基胺基羰基】-5-甲氧 基-6-(4-甲基六氮此讲-1-基丨嘴， 5-氣-2,3-二氮-6-(4-甲基六氮 讲-1-基)-1-[4，(5-甲基-1，2,4-嘮二唑-3_基)笨基胺基羰基】-1H_吲哚， 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 5-氣-2,3-二氫·Η4_<>甲基-1又4-嘮二唑-5-基)苯基胺基羰 基l·心(4·甲基六氫4讲小基)4Η-吲哚， 5_氣_2,3_二氫-6-(心甲基六氫吡#小基)-μ[3·<嘧啶-2,基氧 基)笨基胺基羰基】4Η-吲哚， 5-氣-2,3-二氮-6-(4-甲基六氮 〇tb 讲-1-基甲基(嗜 峻-2-基)胺基]苯基胺基叛基丨朵》 1 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 509687 A7 B7 五、發明説明（10 ) 5-溴-2,3-二氫呋喃冬基)苯基胺基羰基】·6·(4·甲基六 5·氣-2,3▲二氫各(4-甲基六氫郝讲_1_基)_1_[4<碟吩-3·基)苯 基胺基羰基】4Η-吲哚， 5-澳-2,3-二氮、6-(4-甲基六氮此讲_1_基)雀崎-2-基)苯 基胺基羰基】·1Η·吲哚， 5-氣-2,3-二氮-6-(4-甲基六氮此讲-1-基)-1-[4-(雀魂-2“基)苯 基胺基羰基]， 1 -[4-(5-乙釀基σ塞吩-2-基)苯基胺基叛基]-5-氣-2,3-二氮-6· (4·甲基六氫4讲-1·基)-1Η-吲哚， 1-(5->臭蔡-1-基乙釀基)-5-氣-2,3-二氮_6-(4-甲基六氮破I讲-1*· 基)-1Η_,β朵， · 5-氣-2,3-二氫-6-(4-甲基六氫吡讲-1-基)-1 -(8·苯基喹琳-5-基 胺基羰基]_1Η-吲哚， 5-溴-2,3_二氫-6-(4·甲基六氫〇tt讲-1-基)-1_(8_苯基喹秦*5-基 胺基羰基ΗΗ_吲哚， 5-氣_2,3_二氮-ό-(4-甲基六氮此讲-1_基)-1-[2_(2-笨基乙墓) 喹琳-6-基胺基羰基]-1H-吲哚， 經濟部中央標準局員工消費合作社印製 5_氣讎2,3‘二氮-6“(4,甲基六氣1此讲-1·•基麵(1-甲基六氮此 讲冰基)秦4-基胺基羰基】_1Η4丨哚， 5-澳-2,3-二氣-1-[4_(異喹啉冰基)苯基胺基羰基]办(4·甲基 六氫基HH-巧丨哚， 5-氣-2,3-二氫_1·【4-(異喹琳冰基)苯基胺基羰基>6-(4-甲基 六說此讲-1-基丨祿， 12 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（11 ) 5-溴-2,3-二氫-6-(4-甲基六氫基>1-[4<喹琳-3-基)苯 基胺基羰基]4Η-?丨哚， 5·氣-2,3-二氫_6-(4·甲基六氫此讲_1·基)·Η4-(喹琳各基)笨 基胺基羰基】峰， 5-氣_2,3_二氮_6-(4-甲基六氮蛛讲-1-基甲基^1，2,3,4-四氫異嚎基)胺基羰基】-m-吲#， 5-溴-2,3-二氫_6-(4-甲基六氫吡啡-1-基甲基-1，2,3,4· 四氫異喹琳-7_基)胺基羰基】-1Η-吲嗦， 5-溴-2,3-二氫-6-(4-甲基六氫毗_小基)小[4-(喹琳_8_基)笨 基胺基羰基]-1H·吲哚， 5-氣-2,3-二氮-6-(4-甲基六氧4b讲-1-基)-1-[4-(者琳-8-基)苯 基胺基羰基]-1H-吲哚， · 5-氣-2,3-二氫嗦β圭小基)笨基胺基魏基]-6-(4-甲基六 氮此讲-1-基)-1^1-1|?丨1|朵， 5-氣_2,3-二氮-6-(4-甲基六氮此讲-1-基)-l-[4-(〇tb唆-4-基)苯 基胺基羰基】-1Η·吲哚， 2,3麵二氫睡5·甲氧基·6<4-甲基六氟此_·1麵基)小[(8讎苯基喹啉 -5-基)胺基羰基】·1Η-吲哚， 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 5-氣-2,3-二氫-6-(4-甲基六氫吡4小基)_1-[(8-笨墓喹淋冰 基)胺基幾基:ΗΗ-吲哚， 5->臭-2,3^·二氮_6-(4-甲基六氮此脅·!-基)-1-[(8-苯基音琳_4“ 基)胺基羰基】rlH-吲哚， 2,3-二氩-5-甲氧基木(4-甲基六氫吡畊4-基)士[(8_苯基喹琳 斗基)胺基羰基]-1Η-吲哚， 13 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） A7 __-_— _B7 五、發明説明（l2 ) 5-氣.2,3-二氫小㈣扁二甲基“六氫吡基)各甲基苯基 胺拳幾基]各(4_甲基六虱!恍_·!·基)·识_$♦， 5-氣-2,3-二氧·1_[3_甲基邻:甲基六氫此蟒_2,基)苯基联基 羰基】各(4·甲基六氫吡丨嗓， 5養2,3_二氫-H3.甲基邻_甲基缝此__2_基)苯基胺基 幾棊】-6-(4-甲基六氫吡讲小基)4Η弓陳， 2,3-二氩-5·甲氧基小[3_甲基+•甲基六氫此讲咎基)笨基 胺基羰基】_6-(4-甲基六氫赴參^基^挪弓丨碌， 5-氣-2,3-二氫-1例6-甲基六氣此讲1基)萘士基胺基羰 基]-6-(4·甲基六氫北_小基)_1乐1»5|啼， 5*氣·2>二氫-6·(4-乙基六氩吡蟒_μ基化叫吡咬冰基)萘-1-基胺基羰基]·1Η-^哚， · 5-氣_2,3_二氫木(4·乙基六氩吡讲+基)-叩乂此唆冰基)蔡· 1-基胺基羰基]·1Η_啕哚， 5-氣-2,3-二氫_6-(六氫〇Λ哜小基)++(吡啶斗基)萘_1_基胺 基羰基]_1H-吲哚鹽酸顰， 5-氣-2,3-二氫‘6‘(六氩4讲-μ基)4_[5^(畎啶》4_基)萘-1-基胺 基羰基】4Η-吲嗦鹽酸騍， 5-氣_2,3-二氫春(4_甲基六氮此__ 1，基)_ η4彳塔讲各基)笨 基胺基羰基]_1Η_吲哚， 5-溴-2,3_二氫4(4-甲基六氩吡讲-1，基)-1-[4·(嗒讲‘3_基)笨 基联基羰基】4ΚΗ1哚， 5_氣-2,3-二氫-6·(4·甲棊六氫碳讲-1_基)-144_(毗讲-2，基)笨 基胺基羰基】-1Η-吲哚， 141T 509687 A7 B7 V. Description of the invention (9) 5-Mo-2,3-diazine ** 6 · (4-methylhexazine 0ffc speaking-1-yl) -1- [4- (2 · Methyl Otfc, 4-yl) phenylamino-carbonyl] -1H-1? 丨 peak, 5-atom 2,3 diazenium-6, (4-methylhexaoxone to talk about -1 " Group) "» 1 · [4 · (2-methyl this bitine 4 * group) benzylaminocarbonyl fluorene-1Η · indole, 5-amino-2,3 · dihydro · fluorene 4- (2,6 -I-methyl this pyridin-4.yl) phenylaminocarbonyl group] each (4. methyl hexazine this -1-yl)-1Η-1? 丨 peak, 5-bromo-2,3-dihydro -1 · [4 · (2,6-dimethylpyridyl) phenylaminocarbonyl group] _6- (4, methylhexahydropyridyl-4-yl group> 1Η-indole, 2.3-dihydro -Fluorene 4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylhexahydrobi-4-yl) -1fluorene-indole , 5-Ga-2,3. Dihydro-1- [4 · (2,6 · Dimethylpyridinyl) phenylaminocarbonyl] each (4-methylhexahydronoryl) 4Η-, , F 5-brook-2,3-diazol_1- [4 · (2,6-dimethylbenz-3-yl) phenylaminoquinyl] -6- (4-methylhexazine Speaking of a 1-yl group, 2.3-diamidine [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -5-methoxy-6- (4-methylhexa Nitrogen is this -2,3-diazide-6- (4-methylhexazide-1-yl) -1- [4, (5-methyl-1,2,4-fluorenediazole-3_yl) benzyl Aminoaminocarbonyl] -1H_indole, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 5-Gas-2,3-dihydro · 氢 4_ < > A -I-1 and 4-fluorenediazol-5-yl) phenylaminocarbonyl l.heart (4.methylhexahydro-4), 4 基 -indole, 5_gas_2,3_dihydro- 6- (cardiomethylhexahydropyridine # 小 基) -μ [3 · < pyrimidin-2, yloxy) benzylaminocarbonyl] 4Η-indole, 5-gas-2,3-diaza- 6- (4-methylhexaazine 〇tb Talking about 1-ylmethyl (Analytical-2-yl) amino] phenylamino group 丨 Door》 1 This paper size applies to China National Standard (CNS) Α4 Specifications (210 X 297 mm) 509687 A7 B7 V. Description of the invention (10) 5-Bromo-2,3-dihydrofuranyl) phenylaminocarbonyl] · 6 · (4 · methylhexa-5 · gas -2,3 ▲ Dihydro (4-methylhexahydroalkano_1_yl) _1_ [4 < diephen-3 · yl) phenylaminocarbonyl] 4Η-indole, 5-A-2, 3-diazepine, 6- (4-methylhexaazine_1-yl) kisaki-2-yl) phenylaminocarbonyl group] · 1Η · indole, 5-gas-2,3-diazine -6- (4-methylhexaaza Speaking of -1-yl) -1- [4- (Chrysentamine-2 "yl) phenylaminocarbonyl], 1- [4- (5-Ethyl sigmaphen-2-yl) phenylamino Sulfuryl] -5-Gas-2,3-diaza-6 · (4 · methylhexahydro-4 讲 -1 · yl) -1Η-indole, 1- (5- > Ethyl group) -5-Ga-2,3-diazine-6- (4-methylhexaazalyl I -1 * · radical) -1Η_, β flower, · 5-Gas-2,3-di Hydrogen-6- (4-methylhexahydropyridin-1-yl) -1-(8 · phenylquinolin-5-ylaminocarbonyl) _1Η-indole, 5-bromo-2,3-di Hydrogen-6- (4-methylhexahydro-t-l-yl) -1_ (8-phenylquinqin * 5-ylaminocarbonylfluorene_indole, 5-gas_2,3_diazine -ό- (4-methylhexaazine-1_yl) -1- [2_ (2-benzylethyl tomb) quinine-6-ylaminocarbonyl] -1H-indole, Central Standard of the Ministry of Economic Affairs Bureau's Consumer Cooperatives printed 5_ air radon 2,3 'diazo-6 "(4, methyl hexa-gas 1 this talk-1 · • base surface (1-methyl hexazine this ice-based) Qin 4- Aminoaminocarbonyl] _1Η4 丨 indole, 5-o-2,3-digas-1- [4_ (isoquinolineicelyl) phenylaminocarbonyl]] (4 · methylhexahydrolHH-Cl Indole, 5-amino-2,3-dihydro_1 · [4- (isoquinolinyl) phenylaminocarbonyl > 6- (4-methylhexanone 12 This paper size applies to China Standard (CNS) A4 (210X297 mm) 509687 A7 B7 V. Description of the invention (11) 5-Bromo-2,3-dihydro-6- (4-methylhexahydro) > 1- [4 < Quinolin-3-yl) phenylaminocarbonyl] 4Η-? 丨 indole, 5 · Ga-2,3-dihydro-6- (4 · methylhexahydro this _1-yl) · Η4- ( Quinolinyl) benzylaminocarbonyl] peak, 5-Ga_2,3_diaza_6- (4-methylhexaazapyridin-1-ylmethyl ^ 1,2,3,4- Tetrahydroisofluorenyl) aminocarbonyl] -m-ind #, 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridin-1-ylmethyl-1,2,3 , 4 · tetrahydroisoquinolin-7-yl) aminocarbonyl group] -1Η-indionium, 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridyl) small [ 4- (Quilin-8-yl) benzylaminocarbonyl] -1H · indole, 5-Gas-2,3-diazine-6- (4-methylhexaoxy 4b) -1-yl)- 1- [4- (Zhelin-8-yl) phenylaminocarbonyl] -1H-indole, · 5-Gas-2,3-dihydrofluorenyl beta guanyl) benzylaminoweiyl]- 6- (4-methylhexaaza-1--1-yl) -1 ^ 1-1 |? 丨 1 | Flower, 5-Ga_2,3-diaza-6- (4-methylhexaazine Speaking of 1-yl) -l- [4- (〇tb 唆 -4-yl) phenylaminocarbonyl] -1Η · indole, 2, 3 dihydrogen, 5 · methoxy · 6, < 4- Methyl hexafluoro this -1 side group) small [(8 雠 phenylquinoline -5-yl) aminocarbonyl] · 1Η-indole, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 5-Gas-2,3-Dihydro-6 -(4-methylhexahydropyridine 4 small group) _1-[(8-benzylquinocylenyl) amino group: fluorene-indole, 5- > odor-2,3 ^ 6- (4-methylhexaazine ·! -Yl) -1-[(8-phenylylline-4 "yl) aminocarbonyl] rlH-indole, 2,3-diargon-5-methyl Oxywood (4-methylhexahydropyridine 4-yl) [[8-phenylquinolinyl] aminocarbonyl] -1Η-indole, 13 This paper is sized to the Chinese National Standard (CNS) A4 Specifications (210X297 mm) A7 __-_— _B7 V. Description of the Invention (l2) 5-Gas. 2,3-Dihydropyridine dimethyl "hexahydropyridyl" each methylphenylamine ] Each (4_methylhexalice! 恍 _ !! radical) · cognition_ $ ♦, 5-qi-2,3-dioxo · 1_ [3_methyl-ortho: methylhexahydro this python_2 , Yl) phenylbiphenylcarbonyl] Each (4-methylhexahydropyridine, 5-amino-2,3-dihydro-H3.methyl ortho-methyl棊] -6- (4-methylhexahydropyridine) 4Η Gongchen, 2,3-diargon-5 · methoxy small [3-methyl + • methylhexahydro] stupid Aminocarbonyl] -6- (4-methylhexahydroxanthyl), alkoxy, 5-gas-2,3-dihydro-1 Example 6-methylhexaki 1-naphthyl Aminocarbonyl] -6- (4 · methylhexahydronor_small group) _1le 1 »5 | cr, 5 * gas · 2 > dihydro-6 · (4-ethylhexahydropyrazine_μyl Called pyridyl) naphthyl-1-ylaminocarbonyl] · 1Η- ^ indole, · 5-Gas_2,3_dihydrowood (4 · ethylhexahydropyridine +)-this唆 Bingyl) Cai · 1-ylaminocarbonyl] · 1Η-oxoindole, 5-Ga-2,3-dihydro-6- (hexahydro〇Λ 哜 small group) ++ (pyridinyl) naphthalene_ 1-Aminoaminocarbonyl] 1H-indole pyrene hydrochloride, 5-gas-2,3-dihydro'6 '(hexagonal 4-le-yl) 4_ [5 ^ (pyridine> 4-yl) naphthalene- 1-ylaminocarbonyl] 4】 -indiofluorene hydrazone, 5-gas-2,3-dihydrochun (4-methylhexaaza this _ _ 1, radical) η4 彳 amines) Carbonyl] _1Η_indole, 5-bromo-2,3_dihydro 4 (4-methylhexapyridine-1, yl) -1- [4 · (Dadan'3_yl) benzyl Carbonyl] 4KΗ1 indole, 5-Ga-2,3-dihydro-6 · (4 · formamidine hexahydrocarbon-1—yl) -144_ (Vonyl-2, yl) benzylaminocarbonyl]- 1Η-indole, 14

509687 A7 B7 五、發明説明（l3 ) 5_>臭-2,3-二氮τ6-(4“甲基六氮讲-1-基)-1-[4-(赴讲-2-基)苯 基胺基羰基】4H-吲哚， 5-氣-2,3-二氫«4-甲基六氧吡嵴小基)-1-[(2-笨基畎啶_5-基)胺基齡基】-m·吲哚， 5_溴_2,3華二皇·6·(4·甲基六氮此讲·1讎基)讎1-[(2_苯基此唆_5_ 基)胺基羰基]，1H-吲哚， 5-氣-2糸二氫-1-[4-(6•甲基嗒讲-3-基)苯基胺基羰基】-6-(4-甲基六氫毗嵴·1-基)4H-湖哚， 5_漠-2,3-二氮·1-[4-(6-甲基塔讲_3·基)苯基胺基魏基】-6-(4-甲基六氫基)-1Η-吲哚， 5,氣-2,3-二氮-6·(4-甲基六氮此讲-1-基)-l-[4^(4t唆-3-基)笨 基胺基羰基】1H·吲哚， ， 5-氣-2,3-二氫-H4-(5-甲基嘮唑-2-基)笨基胺基羰基]-6-(4-甲基六氩4b畊-1-棊)-1Η-吲哚， 2,3-二氫-5-甲氧基-l-[4-(5-甲基嘮唑-2-基)苯基胺基羰辱】各 (4_甲基六氫此讲-1-基)·1Η-吲哚， 5-溴-2,3-二氫-1_[4<5-甲基嘮唑-2-基)苯基胺基羰基】-6·(4-甲基六氮此讲-1*基丨碌， 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 5-氣-2>二氫甲棊吡唑+基)苯基胺基羰基]-6-(Φ· 甲基六氫毗讲·1_：^)·1Η·吲嗦， 5-溴-2>二氩小【4-(1-甲基毗唑冰基)笨基胺基羰基]-6-(冬 甲基六氫吡4-1-基>1拓吲哚， 5-氣-2,3-二氫小[4’-氰基U基聯苯基-4-胺基羰基]·6-(4-甲基六氫吡讲-1-基>4Η-吲哚， 15 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 509687 Α7 Β7 五、發明説明（14 ) 5-溴-2,3·二氫小[4’-氰基-3f-甲基聯苯基4-胺基羰基]各(4-甲基六氫硃嵴小基)-1H-吲哚， 5-氣_2,3-二氫-1-[4·(2·甲基六氟此啡；基)苯基胺基羰基]各 (4-甲基六氫4嵴-1-基)-1Η·巧丨哚， 5-溴-2,3-二氫小[4-(2“甲基六氫此蟒-5·基)苯基胺基羰基】各 (4-甲基六氫此讲麵1-基)4Η_吲哚， 5-氣-2,3-二氫-Η5<3-甲基_1，2,4_嘮二唑-5-基)萘-1-基胺基 魏基】*6-(4·甲基六氮基’ 2,3-二氫-5-甲氧基_l-[5-(3-甲基-1，2,4-噚二唑-5-基)萘小基 胺基羰基H-(4-甲基六氫此基)-1Η-吲哚， 5-漠_2,3·二氮-l-[5-(3-甲基-1，2,4-崎二逢-5-基)蔡-1-基胺基 魏基ί·6-(4-甲基六氮讲-1-基yiH·11?卜朵’ · 5-氣-2,3-二氫_1-[5-(5·甲基嘮唑-2-基)萘小基胺基羰基】_6_ (4-甲基六氩吡讲小基)-1Η-!Ι哚， 二氩各甲氧基-H>(5-甲基嘮唑-2-基)萘4-基胺基羰 基]-6_(4-甲基六氮讲-1-基)丨哮， 5-溴_2,3，二氮-1_[3-甲基冰(會唆-2-基)苯基胺基魏基]-6«(4-甲基六氫曲4小基>1Η-吲哚， 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 2,3_二氫冰f氧基‘Η3-甲基冰(嘧啶-2-基)苯基胺基羰基Ιό#-甲 基六氩吡讲-1-基 >1Η‘吲哚， 5-氣·2,3_二氩-6-(4-甲基六氫吡讲小基)4_[3_甲基啶-2,基)装基胺基戴基】-ΙΗ-βΙ碌， 5-溴-2,3-二氫小[3-甲基·4-(嘧啶-5·基)苯基胺基羰基]，6·(4-甲基六氫吡讲-1-基)4Η-吲哚， 16 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 509687 經濟部中央標準局員工消費合作社印製 Α7 Β7 五、發明説明（15 ) 5_氣-2,3·二氫-1必甲基斗(嘧咬_5_基)苯基胺基羰基】邻· 甲基六氫毗讲-1-基)4H-吲哚， 2,3d5·甲氧基邻4基+(_+基)苯基胺基羰基】· 6-(4-甲基六氣I此讲-1-基)-iff·»!丨味， 5善2,3-二氩4?[4_(2,6-二甲基此啶斗基>3_甲基苯基胺基 羰基]-6-(4-甲基六氫吡4-1_基)-1Η_«5丨痛， 2.3- ‘氫-5·甲氧基-ΐ-[4·(2,6-二甲基吡啶斗基)各甲基笨基 胺基羰基Η<4-甲基六氩赴_-ΐ·基)_1Η_，哮， 5_氣-2,3-二氫W2,6_二甲基吡啶4_基)萘+基胺基羰 基】-6-(4-甲基六氫此讲-i-基， 5,漠·2,3·;氫小[5〇二甲基吡啶+基)萘·t•基胺基羰 基】各(4-甲基六氫此讲-μ基)‘ιη·吲哚， ， 2.3- 二氫W2,6-二甲基此务4-基)萘-^基胺基羰基】冬(4_ 甲基六氫畎基)-1Η-吲哚， 或其醫藥上可接受鹽類。 較佳之式(I)化合物的鹽類為醫藥上可接受鹽類。此等 包括酸加成鹽，例如鹽酸鹽、溴酸鹽、磷酸鹽、乙酸鹽、 延胡索酸颦、馬來酸鹽、酒石酸鹽、檸檬酸鹽、草酸鹽、 甲磺酸盥及對·甲苯磧酸鹽。 特定之式(I)化合物係能以立體異構形式存在。應瞭解 到本發明包含式(I)化奋物所有幾何和光學異構物形式，《 及其包抟消旋物之混合物。 本發明化合物可像用習於該項技藝所知方法製備得。 本發明更進之方面係提供一種用於式(I)化合物或其醫藥上 17 本紙張尺度適用中國國家標隼（CNS ) Α4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁)509687 A7 B7 V. Description of the invention (l3) 5_ > Odor-2,3-diazine τ6- (4 "methylhexazine-1-yl) -1- [4- (Go to lecture-2-yl) benzene Aminoaminocarbonyl] 4H-indole, 5-gas-2,3-dihydro «4-methylhexaoxopyridine small group} -1-[(2-benzylpyridin-5-yl) amino group Age group] -m · indole, 5_bromo_2,3 huanghuang · 6 · (4 · methylhexaazine · 1 雠 yl) 雠 1-[(2_phenyl 唆唆 _5_ group ) Aminocarbonyl], 1H-indole, 5-Gas-2Hydroxydihydro-1- [4- (6 • methyldaquin-3-yl) phenylaminocarbonyl] -6- (4-methyl Hexahydropyridine · 1-yl) 4H-hydrododene, 5-mo-2,3-diazine · 1- [4- (6-methyl palladium_3 · yl) phenylaminoweiyl] -6- (4-methylhexahydro) -1Η-indole, 5, Ga-2,3-diazine-6 · (4-methylhexaazine-1-yl) -l- [4 ^ (4t 唆 -3-yl) benzylaminocarbonyl] 1H · indole, 5-Ga-2,3-dihydro-H4- (5-methyloxazol-2-yl) benzylamino Carbonyl] -6- (4-methylhexaargon 4bg-1--1-)-1H-indole, 2,3-dihydro-5-methoxy-l- [4- (5-methyloxazole -2-yl) phenylaminocarbonyl]] (4-methylhexahydro-1--1-yl) · 1Η-indole, 5-bromo-2,3-dihydro-1_ [4 < 5- Methyloxazol-2-yl) phenylaminocarbonyl] -6 · (4-methylhexazine this-1 * Baseline, printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) 5-Gas-2 > Dihydropyridazole + yl) phenylaminocarbonyl]- 6- (Φ · methylhexahydropyridine · 1 _: ^) · 1Η · indole, 5-bromo-2 > diargon [4- (1-methylpyrazolyl) benzylaminocarbonyl] -6- (Derbomethylhexahydropyridin 4-yl) > 1 indole, 5-Ga-2,3-dihydro small [4'-cyanoU-biphenyl-4-aminocarbonyl ] · 6- (4-methylhexahydropyridin-1-yl)> 4Η-indole, 15 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 509687 Α7 Β7 V. Description of the invention ( 14) 5-bromo-2,3 · dihydro small [4'-cyano-3f-methylbiphenyl 4-aminocarbonyl] each (4-methylhexahydrocinnabaryl) -1H-ind Indole, 5-qi_2,3-dihydro-1- [4 · (2 · methylhexafluorobenzyl; yl) phenylaminocarbonyl] each (4-methylhexahydro-4-fluoren-1-yl ) -1Η · dodo, 5-bromo-2,3-dihydro small [4- (2 "methylhexahydro this python-5 · yl) phenylaminocarbonyl] each (4-methylhexahydro In this case, 1-yl) 4Η-indole, 5-Ga-2,3-dihydro-fluorene 5 < 3-methyl-1,2,4_fluoradiazol-5-yl) naphthalene-1-ylamine Kiweiki * 6- (4-Methylhexazyl '2,3-dihydro-5-methoxy-1- [5- (3-methyl-1,2,4-fluorenediazole-5-yl) Naphthylamino carbonyl H- (4-methylhexahydro this group) -1Η-indole, 5-mo_2,3 · diaza-1- [5- (3-methyl-1,2, 4-Sullenyl-5-yl) Cai-1-ylaminoweiyl, 6- (4-methylhexazine-1-ylyiH · 11? Budol '· 5-Gas-2,3 -Dihydro_1- [5- (5 · methyloxazol-2-yl) naphthalene small amine carbonyl group] _6_ (4-methylhexahydropyridine) -1 Η-! Ι indole, diargon Each methoxy-H> (5-methyloxazol-2-yl) naphthalene 4-ylaminocarbonyl group] -6- (4-methylhexazine-1-yl), 5-bromo_2 , 3, diazine-1_ [3-methylice (Hydroxy-2-yl) phenylaminoweilyl] -6 «(4-methylhexahydro-4-small group> 1 & -indole, economical Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China (Please read the precautions on the back before filling out this page) 2,3_dihydroice foxy'Η3-methyl ice (pyrimidin-2-yl) phenylaminocarbonyl Ιό # -Methylhexahydropyridin-1-yl > 1Η'indole, 5-Ga · 2,3_diargon-6- (4-methylhexahydropyridine) 4_ [3_ 甲Pyrimidin-2, yl) aminopyridyl] -I-β-β, 5-bromo-2,3-dihydro small [3-methyl · 4- (pyrimidin-5 · yl) phenyl Carbonyl group], 6 · (4-methylhexahydropyridin-1-yl) 4Η-indole, 16 This paper size applies to China National Standard (CNS) A4 (210 × 297 mm) 509687 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the consumer cooperative A7 B7 V. Description of the invention (15) 5-Gas-2,3 · dihydro-1 bismethyl (pyrimidine_5_yl) phenylaminocarbonyl] o-methylhexahydropyridine 1-1-yl) 4H-indole, 2,3d5 · methoxy-o- 4-yl + (_ + yl) phenylaminocarbonyl] 6- (4-methylhexazyl I-1-1-yl ) -iff · »! 丨 Taste, 5 good 2,3-diargon 4? [4_ (2,6-dimethyl this pyridyl group> 3-methylphenylaminocarbonyl group] -6- (4 -Methylhexahydropyridine 4-1-yl) -1Η_ «5 丨 pain, 2.3-'hydro-5 · methoxy-fluorene- [4 · (2,6-dimethylpyridinyl) each methyl group Benzylaminocarbonyl fluorene < 4-methylhexaarginyl group (1-methylphenyl) -1, hydrazone, 5-methyl-2,3-dihydro W2,6-dimethylpyridine 4-yl) naphthalene + ylamine Carbonyl] -6- (4-methylhexahydro this-i-yl, 5, Mo · 2,3 ·; hydrogen small [50 dimethylpyridine + yl) naphthalene t-ylaminocarbonyl] Each (4-methylhexahydro-μyl) ′ ιη · indole,, 2.3-dihydroW2,6-dimethyl-4-methyl) naphthalene- ^ aminoaminocarbonyl] winter (4_ Methylhexahydrofluorenyl) -1H-indole, or a pharmaceutically acceptable salt thereof. Preferred salts of the compound of formula (I) are pharmaceutically acceptable salts. These include acid addition salts such as hydrochloride, bromate, phosphate, acetate, lutetium fumarate, maleate, tartrate, citrate, oxalate, mesylate and p-toluene Osmate. Specific compounds of formula (I) can exist in stereoisomeric forms. It is to be understood that the present invention encompasses all geometric and optical isomer forms of hydrazones of formula (I), and mixtures thereof and racemic inclusions. The compounds of the present invention can be prepared by methods known to those skilled in the art. A further aspect of the present invention is to provide a compound of formula (I) or its medicine. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling in this page)

509687 A7 B7 五、發明説明（16) 可接受鹽類褽儀之方法，其包含： (aj·吝其中D .為氮且γ為NH，則將式⑼化合物： Ra-NC(=V) (Π) 其中R和V係如式(!)中職軸錢賴衍生物，與式⑽ 化合牴偁合509687 A7 B7 V. Description of the invention (16) A method for accepting salt funerals, including: (aj · 吝 where D. Is nitrogen and γ is NH, then the compound of formula ⑼: Ra-NC (= V) ( Π) where R and V are derivatives of formula (!), Which are combined with formula ⑽

HNHN

Rb 〇Rb 〇

Rc (請先閲讀背面之注意事項再填寫本頁) (ΠΙ) 其中w、X、R和RM系如式(I)中所定義，或其受保護之衍 生物； 或 ， (b) 若其中D為氮且γ為NH或NR5，則將式(IV)化合物Rc (please read the notes on the back before filling this page) (ΠΙ) where w, X, R and RM are as defined in formula (I), or protected derivatives thereof; or, (b) if any D is nitrogen and γ is NH or NR5, then the compound of formula (IV)

Ra-NH2 或 r\nr5h (iv) 其中R%aR5係如式①中所定義，和式(Πί)化合物一併與適 當尿素形成劑反應； (c) 若其中D為氮，則將式(V)化合物Ra-NH2 or r \ nr5h (iv) where R% aR5 is as defined in formula ①, and react with a compound of formula (Πί) together with an appropriate urea-forming agent; (c) if D is nitrogen, then formula ( V) Compounds

Ra-Y_(C〇)-L2 (V) 其中Ra係如式(I)中所定義， Y為-CHr或和L2係適當脫離基，與式(III)化合物反應； (d) 若其中D為碳或CH，則將式(VI)化合物Ra-Y_ (C〇) -L2 (V) wherein Ra is as defined in formula (I), Y is -CHr or L2 is an appropriate leaving group to react with a compound of formula (III); (d) if D Is carbon or CH, the compound of formula (VI)

Ra-NH2 (VI) 其中Ra係如式(I)中所定義，與式(VII)化合物反應 訂 經濟部中央標準局員工消費合作社印製Ra-NH2 (VI) where Ra is as defined in formula (I) and reacts with a compound of formula (VII)

五 、發明説明（17) L2 0^V. Description of the invention (17) L2 0 ^

(ΥΠ) • Rc 經濟部中央標準局員工消費合作社印製 其中D為碳或CH、W、X、妒和Rc係如式(1)中所定義且 為適當脫離基 且之後，視需f : 移除任何保護基， • 轉換式(I)化合物成另外式⑴化合物， • 形成醫藥上可接受鹽類。 方法(a)中之反應係便於有機溶劑，例如二氣甲烷中實 施〇 方法(b)中之尿素形成劑可為羰基二咪唑、三碳醯氣或 氯，並於惰性有機溶劑，例如二甲基甲驢胺、四氫吱 喃或二氣甲烷中，在室溫或溫升時，於鹼例如三乙胺或α比 。定的存在下完成。 方法(c)中之脫離基L2可為齒素，例如氯基，且反應可 在惰性有機溶劑，例如四氫呋喃或二氣甲烷中，於室溫或 溫升時，在鹼例如三乙胺或此啶的存在下完成。 方法(d)中之脫離基L2可為處素，例如氯基，且反應可 在惰性有機溶劑，例如四氫吱喃或二氯曱烧中，於室溫或 溫升時，在鹼例如三乙胺或此啶的存在下完成。 使用標準技術可將式(I)化合物轉換成另外式(I)化合 物。例如在其中RC為氫的情形中，採用1莫耳當量鹵化Cp6 19 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇><297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 509687 A7 B7 五、發明説明（is ) 經濟部中央標準局員工消費合作社印製 烷和1莫耳當量之遒合的銓，經由習用烷化作用，在惰性 溶劑中使弓〖入Ck燒基為可能。 中間物式(η)、（m)、（iy>、（v)、（vi)和(νπ)化合物可 使用習於該項技藝所知樣準方法製備得。 於上述方法中，習於該項技藝人士應瞭解到須要保護 特定的反應取代基。可使用標準保護和去保護技術。例如 一級胺可經保護成鄰苯二醮亞胺、芊基、苄氧基羰基或三 苯甲基衍生物❶此等基圈可以習於該項技藝所熟知習用方 法移除。 瘦酸基可經保護成酯類β醛和酮基則可經保護成縮 齡、縮_、硫縮醪或硫縮鲷。使用標準條件以達成去保護 作用。 # 5HTia/ib/id 受體拮抗劑，且特別是本發明之化合物預期 有用於CNS障礙，例如心境陳礙，包括憂鬱、季節性情感 障礙和精神抑赞症；焦慮障礙，包括廣泛姓焦慮、恐慌障 礙、曠野恐怖、社會感怖症、強迫性失調和創傷後應激性 精神障礙；記憶失調，包括癡默、遣忘障礙及年齡相關之 記憶不良；飲食行為失調，包括精神性厭食和精神性暴食 症以及睡眠障礙（包括畫夜節律紊亂）之治療P其他〇^ 障礙释、包括運動陳礙，例如帕金森氏病、帕备森氏病中之 癡默、經精神安定蕖誘導帕金森氏徵候群和遲發性運彭障 礙，矽及其他精神障礙之治療* 5HT1A/iri/iD受艟拮抗劑•且特別是本發明之化合物預期 有用於内分泌失調，例如高催乳素血症之治療，血管痙孿 20 (請先閲讀背面之注意事項再填寫本頁) 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 __B7 五、發明説明（！9 ) (特別是在大腦血管系）和高it壓，以及胃勝道失調，其 中涉及能動性和分泌改變之治療。彼等亦可有用於性機能 障礙和低溫之治療。， 本發明亦提供一輕具通式(I)化合物或其生理上可接受 之鹽或溶射合物，用於前述陳礙治療。 於另一方面，本發明提供一種治療前述障礙，包括給 予需要該等具通式(I)化合物或其生理上可接受之鹽或溶劑 合物治療之患者有效含董之方法。 特別是本發明提供一種具通式(I)化合物或其生理上可 接受之鹽或溶劑合物，用於治療或預防憂鬱b 習於該項技藝人士應瞭解到，根據本發明之化合物可 有利地與一種或更多其他種治療劑，例如不同的抗憂镦劑 使用。 本發明亦提供一種醫藥組合物，其包含式(I)化合物或 其醫藥上可接受之鹽，以及醫藥上可接受之載髏。 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 本發明醫藥组合物，適合於室溫及大氣壓下，藉由摻 合而製備得，通常採用口脤、非經勝道或直腸給藥，且就 此點而論，其可以是錠谢、膠囊费丨、口服液饞製劑、散谢、 顆鈒劑、含片、可再組成散劑、可注射或輸注溶液劑或懸 浮劑或栓劑式。可經〇脲給藥之组合物一般為較佳。 用於口服給藥之餿鲭及膠囊劑可以是單位劑型，並可 包含習用賦形劑，例如黏合劑、填充劑、壓片潤滑劑、崩 解劑以及可接受之潤濕劑。此等錠劑可根據正常製藥實際 操作中所熟知方法塗復。 21 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公釐 1 嫌 ' 經濟部中央標準局員工消費合作社印製 509687 A7 ____B7 五、發明説明（2〇 ) 口服液體製劑可以是，例如水性或油性懸浮劑、溶液 剤、乳液、糖漿或酏劑形式，或為乾燥產品形式，在使用 前與水或適宜載體再組成。磚等液體製劑可含有習用摻和 劑，例如懸浮劑 >乳化劑、非水性載體（其可包括食用油）、 防腐劑，以及，若需要，習用調味劑或著色劑。 用於非經勝道給藥時，流體單位劑型係利用本發明化 合物或其醫藥上可接受之鹽以及滅菌載艎製備得。此化合 物，視所使用截體及濃度雨定，可或為懸浮於或為溶解於 該載體中。於製備溶液劑時，在填充於適宜管瓶或安瓿中 並於密封之前，可將此化合物溶解以用於注射並經過濾滅 菌。有利地，係將佐劑，例如局部麻醉射、防腐劑及緩衝 劑溶解於載讎中。為增強安定性，可將此組鉴物待經填充 入管瓶後，進行冷凍並於真空下將水移除。除化合物係懸 浮於賦形劑申而非溶解於賦形劑中，以及無法以過濾完成 滅菌之外’非經勝道懸浮脅丨本質上係以相同的方式製備而 得。此化合物在懸浮於無菌載體之前，可藉由暴露於環氧 乙烷滅菌。有利地，可將界面活性劑或滴溼劑包括於此組 合物中，以促進化合物均勻分布。 此組合物按重量計，可含有自OJ%至99%，較佳係按 重查計，含自10至60%活性物質，視給藥方法两定4 使用於前逮障礙治療之化合物剤量，按照常例係隨疾 病嚴童性、受害者重t，以及其他相似因素而改變。然雨， 作為一般的指導原則，適宜之單位劑量可為〇.〇5至1Θ00毫 克，較適宜地係1·0至200毫克，且該等草位劑董每日可經 22 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先聞讀背面之注意事項再填寫本頁) 訂 509687 Α7 Β7 五、發明説明（21 ) 經濟部中央標準局員工消費合作社印製 超過一次給藥，例如每曰二或兰次。該治療可延蹟數週或 數月。 底下實施例係用作說明丰發明化合物之製備。 說明1 4-溴_义甲基笨基奠氰酸鳙 將乙二醯氣（11·94束，0.094莫耳）加至存於二氣甲燒（3〇〇 毫升）之經攪拌4·溴_3_甲基笨Υ酸（1〇 〇克，0.047莫耳） 懸浮液中，隨後滴入3滴DMF。將此混合物於室溫下挽拌 60小時，然後於真空中濃縮該溶液，以生產出紅色油狀之 醢基氣。將此物質再溶解於二氣甲烷（300毫升）中並冷卻 至0°C。加入四丁基块化銨，隨後加入存於水（75毫升） 之疊氮化鈉（4.36克，0.066莫耳）溶液，並腌此混合物於 〇°C下激烈攪拌3小時，然後以水（200毫升）稀釋並將二 氣甲烷層分離，乾燥（Na2S04)並於真空中濃縮（但非完 全至乾），獲得醯疊氮淺橙色固體❹將此物質溶解於甲苯 (300毫升）中並於回流攪拌加熱1小時，然後冷卻並於真 空中濃縮，獲得紅棕色油狀標題化合物（9·42克，95%)。 lH NMR (250MHz, CDC13) δ (ppm) ί 7.54 (d, 1Η) » 7.06 <d, 1H) ? 6:8S (d4 1H)，146 (s，3H)。 說明2 參4-棊>萘4-基鱷 將經挽拌蕃於U-二甲氧基乙烷（4〇0毫升）之4·溪萘•式· 基胺（10克，45牽莫耳）與含碳酸鈉（14克）之水（100 毫升）从氬氣沖洗加入肆(三苯膦)把⑼（2·75克，2.4毫 23 (請先閲讀背面之注意事項再填寫本頁} -訂 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 _ B7 五、發明説明（22 ) 莫耳），隨後加入“此啶硼酸（5·7克，46毫莫耳）並將該 混合物於回流下加熱5小時。將此混合物於真空中濃縮至 棕色淤漿並在二氣甲烷和水孓間進分配。該水相進一步 以二敫甲烷萃取，並將經組合之有機相乾燥（Na2S04)且 於真空中濃縮得棕色固體（13·2克）。藉由急驊層析術， 以乙酸乙酯溶析而將該固體純化，獲得黃色結晶固體之標 題化合物（7,8充，78%)。 lH NMR (250MHz，CDC13) δ (ppm) : «说(4 2Η)，7·90 (d， 2H)，7·30 (m，5H)，6·84 (d，1H)，4·32 (s，2H) 〇 說明3 啶本基萘甲酸 使用類似於說明2之方法，自5_溴萘甲酸(έΡ547442Α1) 與4-此啶硼酸製備得本標題化合物0 ^NMR(250MHz, d6DMSO) δ (ppm) ： 8.75 (d, 1H) * 8.56 (dd, 2H)，7.98(4 IH)，7·78<41H)，7.56(t，1H)，745-7.34 (m， 4H)〇 說明4 食4基)萘·1-基異氰酸癱 使用類似於說明1之方法，自咬-4·基萘甲酸(〇3) 製備得本標題化舍物。 lH NMR (250 Μίίζ, CDC13) 5 (ppm) ： 8.74 (d, 2H) ^ 8.21 (4 IH)，7·61，7·69 (m，2H)，7·49-7·33 <m，5H)， 說明5 44*fc啶I基)苯麽 24 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐) "' " (請先閲讀背面之注意事項再填寫本頁)(ΥΠ) • Rc Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs where D is carbon or CH, W, X, jealousy, and Rc are as defined in formula (1) and are appropriately detached from the base and afterwards, if necessary f: Remove any protecting groups, • convert a compound of formula (I) into another compound of formula ⑴, • form a pharmaceutically acceptable salt. The reaction in method (a) is convenient for organic solvents. For example, the diuretic methane is used. The urea-forming agent in method (b) can be carbonyldiimidazole, tricarbonium or chlorine, and in an inert organic solvent, such as dimethylformamide. In methylmethanamine, tetrahydromethane or digas methane, at room temperature or temperature rise, in a base such as triethylamine or alpha ratio. Completed in the presence of a certain. The leaving group L2 in the method (c) may be a dentin, such as a chloro group, and the reaction may be in an inert organic solvent, such as tetrahydrofuran or digasmethane, at room temperature or temperature rise, in a base such as triethylamine or the like This is done in the presence of pyridine. The leaving group L2 in the method (d) may be a process, such as a chloro group, and the reaction may be in an inert organic solvent, such as tetrahydrofuran or dichloroarsine, at room temperature or at a temperature rise, in a base such as This is done in the presence of ethylamine or this pyridine. Compounds of formula (I) can be converted to additional compounds of formula (I) using standard techniques. For example, in the case where RC is hydrogen, 1 mole equivalent halogenated Cp6 19 is used. This paper size is applicable to the Chinese National Standard (CNS) A4 specification (21〇 > < 297mm) (Please read the precautions on the back before Fill out this page) Order 509687 A7 B7 V. Description of the invention (is) Printed alkane and 1 mole equivalent of plutonium produced by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs through conventional alkylation in an inert solvent. It is possible to add Ck. Intermediate compounds (η), (m), (iy>), (v), (vi), and (νπ) can be prepared using standard methods known in the art. In the above method, Those skilled in the art should understand that specific reactive substituents need to be protected. Standard protection and deprotection techniques can be used. For example, primary amines can be protected to o-phthalenedimine, fluorenyl, benzyloxycarbonyl, or trityl derivatives These base rings can be removed by methods familiar to the art. Lean acid groups can be protected to form ester β aldehydes and keto groups can be protected to reduce age, shrinkage, sulfur shrinkage, or sulfur shrinkage. Sea bream. Use standard conditions to achieve deprotection. # 5HTia / ib / id Receptor antagonists, and especially the compounds of the present invention are expected to be useful for CNS disorders, such as mood disorders, including depression, seasonal affective disorders and mental depression Praise; anxiety disorders, including widespread surname anxiety, panic disorder, wilderness horror, social phobia, obsessive-compulsive disorder, and post-traumatic stress disorder; memory disorders, including obesity, amnesia, and age-related memory disorders Eating disorders Includes treatment of anorexia nervosa and bulimia, and sleep disorders (including dysrhythmia). Other disorders, including movement disorders, such as Parkinson's disease, obesity in Parkesson's disease, Psychiazolium induces Parkinson's syndrome and treatment of delayed onset of dysfunction, silicon and other mental disorders * 5HT1A / iri / iD receptor antagonists • and especially the compounds of the present invention are expected to be useful for endocrine disorders, such as high Treatment of prolactinemia, vasospasm 20 (Please read the precautions on the back before filling this page) The paper size of this edition applies to Chinese National Standard (CNS) A4 (210X297 mm) 509687 A7 __B7 V. Description of the invention ( 9) (especially in the cerebral vasculature) and high it pressure, as well as gastric disorders, which involve the treatment of motility and secretory changes. They can also be used for the treatment of sexual dysfunction and hypothermia., The present invention also provides A compound of general formula (I), or a physiologically acceptable salt or solvate thereof, for use in the treatment of the aforementioned disorders. In another aspect, the present invention provides a method for treating the aforementioned disorders, including An effective method for treating a patient in need of such a compound of general formula (I) or a physiologically acceptable salt or solvate thereof. In particular, the present invention provides a compound of general formula (I) or a physiologically acceptable method thereof. Accepted salts or solvates for the treatment or prevention of depression b Those skilled in the art will appreciate that the compounds according to the present invention may be advantageously used with one or more other therapeutic agents, such as different anti-anxieties The invention also provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable skull. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read first Note on the back side, please fill out this page again) The pharmaceutical composition of the present invention is suitable for preparation by blending at room temperature and atmospheric pressure, and is usually administered orally, indirectly, or rectally, and in this regard It can be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusion solutions or suspensions, or suppositories. Compositions which can be administered via O urea are generally preferred. Mackerel and capsules for oral administration may be in unit dosage form and may contain conventional excipients such as binders, fillers, tablet lubricants, disintegrating agents, and acceptable wetting agents. These lozenges can be applied according to methods well known in normal pharmaceutical practice. 21 This paper size applies to Chinese National Standard (CNS) A4 specifications (210X297 mm 1 suspected to be printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 ____B7 V. Description of the invention (2) The oral liquid preparation can be, for example, aqueous or Oily suspensions, solutions, emulsions, syrups or elixirs, or in the form of dry products, reconstituted with water or a suitable carrier before use. Liquid formulations such as bricks may contain conventional admixtures, such as suspending agents > emulsifiers , Non-aqueous carriers (which may include edible oils), preservatives, and, if necessary, conventional flavoring or coloring agents. When used for non-contrast administration, the fluid unit dosage form utilizes a compound of the present invention or a pharmaceutically acceptable It can be prepared by accepting the salt and sterilized carrier. This compound, depending on the intercept and concentration used, can be either suspended or dissolved in the carrier. When preparing the solution, it should be filled in a suitable vial or ampoule. Before being sealed, this compound can be dissolved for injection and sterilized by filtration. Advantageously, adjuvants such as local anesthetic shots, preservatives and buffers are used. The agent is dissolved in the carrier. To enhance the stability, this group of samples can be filled into a vial, frozen, and the water removed under vacuum. The compound is suspended in the excipient rather than dissolved in the excipient. In the form of preparations, as well as those that cannot be sterilized by filtration, they are essentially prepared in the same way. This compound can be sterilized by exposure to ethylene oxide before being suspended in a sterile carrier. Advantageously, a surfactant or a moisturizing agent may be included in the composition to promote uniform distribution of the compound. The composition may contain from OJ% to 99% by weight, preferably by re-examination, Contains from 10 to 60% of the active substance, depending on the method of administration4 The amount of compound used in the treatment of pre-catch disorders, according to common practice, varies with the severity of the disease, the weight of the victim, and other similar factors. Ranyu As a general guideline, a suitable unit dose may be from 0.05 to 1Θ00 mg, more preferably from 1.0 to 200 mg, and these herbicides can be used in 22 paper sizes per day in China. Standard (CNS) Α4 specification (210X29 7mm) (Please read the precautions on the back before filling out this page) Order 509687 Α7 Β7 V. Description of invention (21) The Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs printed more than one dose, such as two or ten This treatment can be extended for several weeks or months. The following examples are used to illustrate the preparation of the compounds of the invention. Explanation 1 4-Bromo-synylmethylbenzyl cyanate will be ethylene difluoride (11 · 94 Bundle, 0.094 moles) was added to a stirred suspension of 4 · bromo-3-methylbenzylic acid (100 g, 0.047 moles) in digas methylbenzene (300 ml), followed by dripping 3 drops of DMF were added. The mixture was stirred at room temperature for 60 hours, and then the solution was concentrated in vacuo to produce a red oily tritium base gas. This material was redissolved in methane (300 ml) and cooled to 0 ° C. Add tetrabutylammonium bismuth, followed by a solution of sodium azide (4.36 g, 0.066 mol) in water (75 ml), and marinate the mixture under vigorous stirring at 0 ° C for 3 hours, then with water ( 200 ml) diluted and separated the two methane layer, dried (Na2S04) and concentrated in vacuo (but not completely to dry) to obtain 醯 azide light orange solid. This material was dissolved in toluene (300 ml) and It was heated with stirring at reflux for 1 hour, then cooled and concentrated in vacuo to obtain the title compound (9.42 g, 95%) as a red-brown oil. lH NMR (250MHz, CDC13) δ (ppm) ί 7.54 (d, 1Η) »7.06 < d, 1H)? 6: 8S (d4 1H), 146 (s, 3H). Description 2 Ginseng 4- 棊 > Naphthalene 4-based crocodile will be transformed into U-dimethoxyethane (400 ml) in 4 · naphthalene · form · ylamine (10 g, 45 moles) Ear) and water (100 ml) containing sodium carbonate (14 g), rinse with argon and add thallium (triphenylphosphine) (2.75 g, 2.4 mmol 23) (Please read the precautions on the back before filling this page } -The size of the paper used for this edition is in accordance with the Chinese National Standard (CNS) A4 (210X297 mm) printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 _ B7 V. Description of the Invention (22) Moore), and then add "this Boric acid (5.7 g, 46 mmol) and the mixture was heated at reflux for 5 hours. The mixture was concentrated in vacuo to a brown slurry and partitioned between methane and leech. The aqueous phase was further Extract with dichloromethane and dry the combined organic phases (Na2S04) and concentrate in vacuo to obtain a brown solid (13 · 2 g). This solid was dissolved in ethyl acetate by flash chromatography. Purification gave the title compound (7,8, 78%) as a yellow crystalline solid. LH NMR (250 MHz, CDC13) δ (ppm): «Speaking (4 2 ), 7.90 (d, 2H), 7.30 (m, 5H), 6.84 (d, 1H), 4.32 (s, 2H) 〇 Explanation 3 The use of pyrimidinylnaphthoic acid is similar to that of instruction 2 By the method, the title compound was prepared from 5-bromonaphthoic acid (PDP 442442A1) and 4-pyridineboronic acid. 0 NMR (250 MHz, d6DMSO) δ (ppm): 8.75 (d, 1H) * 8.56 (dd, 2H), 7.98 (4 IH), 7.78 < 41H), 7.56 (t, 1H), 745-7.34 (m, 4H). Note 4 Food 4 groups) Naphthalene 1-yl isocyanate is similar to that used in Note 1 The title compound was prepared by self-bite-4.naphthoic acid (〇3). LH NMR (250 Μίζ, CDC13) 5 (ppm): 8.74 (d, 2H) ^ 8.21 (4 IH), 7. · 61,7 · 69 (m, 2H), 7.49-7 · 33 < m, 5H), description 5 44 * fc pyridine I-based) benzene 24 This paper size applies to China National Standard (CNS) A4 specifications ( 210X297 mm) " '" (Please read the notes on the back before filling this page)

509687 A7 B7 五、發明説明（23 ) 使用類似於說明2之方法，自4-溴苯胺與4_赴啶·酸製備 得白色固體（17%)。 lR NMR (250 MHz, d6DMSO) δ (ppm) ： 8.68^8.63 (m> 2H), 7·78-7·68 (m，4H>，6·84 (d，2H)，5.94 (br s，2H)。 說明6 3_氣·4-(ιΛ嚏-4-基)苯磨 使用類似於說明2之方法，將3-氯·4-溴乙醢笨联與4·吨唆 硼馥反應，獲得3-氣*4<此啶+基)6醢笨胺。秦由於2祕 NaOH與乙酵混合物之回流中將此物質加熱6小時水解，獲^ 得淺黃色固體之標題化合物（5·5克，73%)。 lU NMR (250 MHz, CDCI3) δ (pptn) ： 8.^5-8.58 (m, 2H) * 7·38-7·33 (m，2H)，7·13 (d，1H)，6·80 (d，1H)，6:64 (dd，1H), 3.90 (br s，2H)。 辑明7 2,3_二氣_4•(錢·‘基 > 笨按 使用類似於說明2之製備方法，自4-漠二氣乙醯苯胺 與4-吡啶硼酸，隨後經由驗性水解，獲得本標題化合物。 經濟部中央標準局員工消費合作社印製 H NMR (250 MHz, CDCh) δ (ppm) ： $.^4 (d3 2H) ^ 732 (4 2H)，7.G5 (4 m)，6·85 (41H)，4·40 (br s，2H)- 說明8 1· 6 藥基 於室邋下將存於二氣甲烷（100毫升）經攪拌之2,3_二氩各 硝基_1H-吲哚（1〇〇克，〇·61莫耳）以醋酸釺（6》毫升，0.66 莫耳)逐滴處理超過20分鐘。將反應混合物攪拌另2小時， 25 本紙張尺度適财關家標準（CNS ) Α4規格（2丨Q χ 297公釐） 509687 經濟部中央標準局員工消費合作社印製 A7 ____B7 五、發明説明（24 ) 然後以10%Na2C〇3溶液（300毫升）洗滌、乾燥（Na2S04) 並於真空中濃縮，獲得黃色固盤之本標題化合物（125克， 100%) 〇 * 說明9 1-乙麄基冬麼基-2,3Γ上氬·1Η—«1哚 於50 psi下將存於THF( 5500毫升）經攪拌之1·己截基-2,3, 二氳各硝基_1H_吲哚（m，I25束，0·61莫耳）於l〇%p+C (20克）上進行氩化20小時。藉由通過梦藻土管塞過濾以 移除催化劑，並將濾液於真空中濃縮，獲得米黃色固體之 本標題化合物（102克，95%) 〇 ln NMR (250 MHz, CDC13) δ (ppm) ： 7.64 (d, 1H) » 6.92 (d? 1H)，6·34 (dd51H)，4 01 (t，2H)，3·82(brs，2¾):3.06 (t 2H)， 2.19(s，3H)〇 說明10 1·乙龜基_2,3-二氣·6_(4_甲基六氳畎4_1-基>_111·喵嵘 將存於1-丁酵（1800毫升）經攪拌之1_6醢基4·胺基-2,3-二氫-1Η-5丨哚（D9，318克，0·22莫耳）、雙氣乙基甲胺 鹽酸躉（46克，0.24莫耳）及無水碳酸押（肋克，〇,昶莫 耳）混合物於回流下加熱$小時，然後並將另外的雙氣厶 基甲胺鹽酸鹽（25克，0·13莫耳）及瑗睃鉀（41克，0·30 莫耳）加入，並繼續回流3小時。使反應混合物冷卻，缚 後並《水（1000毫升）洗滌。水性洗滌液以乙酸乙_萃取， 並將該萃取物與1_丁酵溶液組合且於真空中濃縮。將棕色 油狀殘餘物（60克）於矽石凝膠上以0-8%Me0H/t)CM溶 26 本紙張纽適财關家轉（CNS )从秘（21GX297公釐） 一 (請先閲讀背面之注意事項再填寫本頁) 、τ 509687 Α7 Β7 五、發明説明（25 ) 經濟部中央標準局員工消費合作社印製 析而層析，得到橙色油，其與醚研磨，獲得米黃色固艎之 本標題化合物（12·2克，22%)。 lU NMR (250 MHz, CDC13) δ (ppm) ： 7.98 (d, 1H) » 7.04 (d, 1H)，6.59(dd，1H)，4.04(t，2H)，3.23-3.i8(m，4H)，110(t， 2H) ’ 2·60-2·53 (m，4H)，134 (s，3H)，2.21 (s，3H) b 說明1Ϊ2,3*二氬*-6-(4^甲基六氬此亦4_基^4||_弓|嗓 使用類似於說明13之方法、自ι·乙醢基-23_二氮_6<4•甲基 六氫4讲小基)-1Η_吲哚(D10)製備得米黃色固體之本標題 化合物（92%)。 lH NMR (250 MHz, CDGI3) δ (ppm) ： 6.98 (dd, 1H) - 6.34- 6·27 (m，2H) ’ 3.53 (t，2k)，3·32 (br s，1H)，3·Π-111 (m，4H)， 2.94 (t，2H>，2·61_2·52 (m，4H)，2·34 (s，3H)。 說明12 1-乙酶基-5-氟-2,3-二氳-6-(4·甲基六氬赴味4·基嗓 在氬氣下於-5°C時，將存於二氣甲烷（1〇〇毫升）之經挽拌 1-乙醯基-2,3-二氫冬(4-甲基六氫毗_小基哚 (D10，1·1克，XK0040莫耳)溶液，以存於DCK1 (10毫 升）之氣代琥珀醯亞胺（〇·73克，CL0054莫耳）溶液逐 滴處理超過15分鐘，然後於-5¾下锯持另0·5小時，並使 其溫至室潭超遍1小畴。以2MHC!酸（60毫升）萃取该反 應混合物，並將該酸筚取物藉由添加固體K2C〇3鹼化，並 以DCM萃取❹將萃取物乾燥（Na2S04)並於真空中濃縮， 獲得米黃色固體之本標輝化合物（1·43克，1〇〇%)。 27 (請先閲讀背面之注意事項再填寫本頁) 、1Τ 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 509687 Α7 Β7 五、發明説明（26 ) ln NMR (250 MHz, CDC13) δ (ppm) ： 8.05 (s, 1H) ♦ 7.15 (s, 1H)，4.06(t，2H)，3.20-3i)5(m，4H)，3.12(t，2H), 2 70-2.55 (叫 4H)，2·37 (s，3H)，2·22 (s，3H)。 說明13 5-|tw2,3-:2L氦各(4_蘩基六氬赴参ι·基嗓 在氬氣下將存於2ΜΗα酸（120毫升）之經攪拌1-乙醯基 -5-氣·2,3、二氫各(4-甲基六氩1此峤·ι_基)-ιη-吲哚（D12，1·4 克，0.0048莫耳）溶液，於回流下加熱5小時。使此反應 混合物冷卻，藉由添加固體K2C03驗化，並以DCM萃取。 將萃取物乾燥（Na2S〇4)，並於真空中濃縮，獲得米黃色 固體之本#題化合物（0·93克，78〇/〇)。 ln NMR (250 MHz, CDC13) δ (ppm) ： 7.07 (s/lH) ^ 6.40 (s5 1H)，3.76 (br s，1H)，3·56 (t，2H)，3.01 (br s，4H)，2.96 (t，2H)， 2.60 (br s，4H)，2.35 (s，3H)。 說明14 乙醮基·5-澳-2,1二氳-6-(4•甲基六氟畎蟒小棊>_ιη·弓丨嗛 在氬氣下於-5°C時，將存於二氣甲烷（100亳升）及甲醇（50 毫升）混合物之經攪拌1·6鏟基_2,3_二氩冬(冬甲基六氫_ 蟒-l-基)-1Η-吲啼（D10，2·0克，0.0077莫耳）混合物，以 苄基三甲基三溴銨（3·14克，0.0081莫耳）逐份處滅超過 20分鐘。使此混合物溫|室溫超過1小時，然後於真宰中 濃縮並將殘餘物溶解於二氣甲烷（150亳升 >,以水（150 毫升）洗滌，轉燥（Na2S〇4)聲於真空中濃_，獲得米黃 色固體之本標題4匕合物（2·52克，97%)。 28 本紙張尺度適用中國國家榡準（CNS ) Α4規格（210Χ297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央標準局員工消費合作社印製 經濟部中央標準局員工消費合作社印製 509687 A7 B7 五、發明説明（27 ) ln imK (250 MHz, CDC13) δ (ppm) ： 8.06 (s, 1H) ^ 7.34 (s9 1Η)，4·06 (t，2Η)，3·13 (t，2Η)，3·07 (brs，4H)，2 06 (br s，4H)， 2·35 ($，3H)，2.21 (s，3H)。509687 A7 B7 V. Description of the invention (23) Using a method similar to that of Note 2, a white solid (17%) was prepared from 4-bromoaniline and 4-pyridine · acid. lR NMR (250 MHz, d6DMSO) δ (ppm): 8.68 ^ 8.63 (m > 2H), 7.78-7 · 68 (m, 4H >, 6.84 (d, 2H), 5.94 (br s, 2H ). Note 6 3_Ga · 4- (ιΛε-4-yl) benzene grinding Using a method similar to that in Note 2, the reaction of 3-chloro · 4-bromoacetamidine with 4 · tonne of borax is obtained. 3-Gas * 4 < this pyridine + group) 6 hydrazine. This material was hydrolyzed for 6 hours under reflux of NaOH and acetic acid mixture to obtain the title compound (5.5 g, 73%) as a pale yellow solid. lU NMR (250 MHz, CDCI3) δ (pptn): 8. ^ 5-8.58 (m, 2H) * 7.38-7 · 33 (m, 2H), 7.13 (d, 1H), 6.80 (d, 1H), 6:64 (dd, 1H), 3.90 (br s, 2H). Compilation 7 2,3_Digas_4 • (Qian · 'Base > Stupid use of a preparation method similar to that of instruction 2, starting from 4-aqueous diethylacetanilide and 4-pyridineboronic acid, and then undergoing an analytic hydrolysis To obtain the title compound. H NMR (250 MHz, CDCh) δ (ppm) printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs: $. ^ 4 (d3 2H) ^ 732 (4 2H), 7.G5 (4 m ), 6.85 (41H), 4.40 (br s, 2H)-Description 8 1 · 6 The medicine is based on a chamber, which will be stored in digas methane (100 ml) with stirring of 2,3_ diargon nitrate 1H-indole (100 g, 0.61 mol) was treated dropwise with europium acetate (6 "ml, 0.66 mol) for more than 20 minutes. The reaction mixture was stirred for another 2 hours. Caiguan Standard (CNS) A4 specification (2 丨 Q χ 297 mm) 509687 Printed by A7 ____B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (24) Then a 10% Na2C03 solution (300 ml) Wash, dry (Na2S04) and concentrate in vacuo to obtain the title compound (125 g, 100%) as a yellow solid plate. ○ * Description 9 1-Ethylpyremyl-2,3Γ on argon · 1Η— «1 Indole at 50 psi Stored in THF (5500 ml) with stirred 1 · hexyl-2,3, difluorinated nitro_1H_indole (m, I25 bundle, 0.61 mol) at 10% p + C ( 20 g) was subjected to argon for 20 hours. The catalyst was removed by filtration through a plug of diatomite, and the filtrate was concentrated in vacuo to obtain the title compound (102 g, 95%) as a beige solid. Ln NMR ( 250 MHz, CDC13) δ (ppm): 7.64 (d, 1H) »6.92 (d? 1H), 6.34 (dd51H), 4 01 (t, 2H), 3.82 (brs, 2¾): 3.06 ( t 2H), 2.19 (s, 3H). Explanation 10 1 Ethyl-2-, 3-digas, 6_ (4_methylhexafluorene, 4_1-yl group), and _111 Fermentation (1800 ml) of agitated 1-6 fluorenyl 4-amino-2,3-dihydro-1 fluoren-5 indole (D9,318 g, 0.22 mol), digas ethyl methylamine hydrochloride 46 g, 0.24 mol) and anhydrous carbonic acid (rib, 0, mol) are heated under reflux for $ hours, and then additional dikisfamidine methylamine hydrochloride (25 g, 0.13 Mol) and osmium potassium (41 g, 0.30 Mole) were added, and the reflux was continued for 3 hours. The reaction mixture was cooled, bound and washed with "water (1000 ml)" . _ The aqueous washings were extracted with ethyl acetate, and the extract composition with 1_ butoxy yeast solution and concentrated in vacuo. Dissolve brown oily residue (60g) on silica gel with 0-8% Me0H / t) CM. 26 papers of New Zealand Finance (CNS) from the secret (21GX297 mm) 1 (please first Read the notes on the reverse side and fill in this page), τ 509687 Α7 Β7 V. Description of the invention (25) Printed and chromatographed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs to obtain an orange oil, which is ground with ether to obtain a beige solid. The title compound (12. 2 g, 22%). lU NMR (250 MHz, CDC13) δ (ppm): 7.98 (d, 1H) »7.04 (d, 1H), 6.59 (dd, 1H), 4.04 (t, 2H), 3.23-3.i8 (m, 4H ), 110 (t, 2H) '2.60-2 · 53 (m, 4H), 134 (s, 3H), 2.21 (s, 3H) b Explanation 1Ϊ2,3 * Diargon * -6- (4 ^ Methylhexagon is also a 4-group ^ 4 || _bow | thorax using a method similar to that of Note 13, from ι · ethenyl-23_diaza_6 < 4 • methylhexahydro, a small group) -1Η-indole (D10) prepared the title compound (92%) as a beige solid. lH NMR (250 MHz, CDGI3) δ (ppm): 6.98 (dd, 1H)-6.34- 6 · 27 (m, 2H) '3.53 (t, 2k), 3.32 (br s, 1H), 3 · Π-111 (m, 4H), 2.94 (t, 2H >, 2.61_2 · 52 (m, 4H), 2.34 (s, 3H). Explanation 12 1-Ethyl-5-fluoro-2, 3-Dihydrazine-6- (4.methylhexaargon to taste. 4.Based at -5 ° C under argon, the 1-ethyl Amidino-2,3-dihydrochrysene (4-methylhexahydropyridyl (D10, 1.1 g, XK0040 mole)) solution to store succinic acid in DCK1 (10 ml) The amine (.73 g, CL0054 mole) solution was treated dropwise for more than 15 minutes, and then sawed at -5¾ for another 0.5 hours, and allowed to warm to room temperature over 1 small domain. With 2MHC! Acid ( 60 ml) of the reaction mixture, and the acid extract was basified by adding solid K2CO3, and extracted with DCM. The extract was dried (Na2S04) and concentrated in vacuo to obtain the standard of beige solid Glow compounds (1.43 g, 100%). 27 (Please read the precautions on the back before filling out this page), 1T This paper size applies Chinese National Standard (CNS) Α4 regulations (210X297 mm) 509687 A7 B7 V. Description of the invention (26) ln NMR (250 MHz, CDC13) δ (ppm): 8.05 (s, 1H) ♦ 7.15 (s, 1H), 4.06 (t, 2H), 3.20 -3i) 5 (m, 4H), 3.12 (t, 2H), 2 70-2.55 (called 4H), 2.37 (s, 3H), 2.22 (s, 3H). Explanation 13 5- | tw2 , 3-: 2L helium each (4-Hexyl hexaargon to go to the base, under the argon will be stored in 2M Ηα acid (120 ml) with stirring 1-ethyl hydrazine-5-gas · 2,3, A solution of each of the dihydrogen (4-methylhexaarginyl) -yl-indole (D12, 1.4 g, 0.0048 mole) was heated under reflux for 5 hours. The reaction mixture was cooled, Assay by adding solid K2C03 and extracting with DCM. The extract was dried (Na2SO4) and concentrated in vacuo to obtain the title compound (0.93 g, 78/0) as a beige solid. ln NMR (250 MHz, CDC13) δ (ppm): 7.07 (s / lH) ^ 6.40 (s5 1H), 3.76 (br s, 1H), 3.56 (t, 2H), 3.01 (br s, 4H) , 2.96 (t, 2H), 2.60 (br s, 4H), 2.35 (s, 3H). Note 14 Acetyl-5-A-2,1difluorene-6- (4 • methylhexafluoropyrene small 棊 > _ιη ·· 丨 嗛 will be stored at -5 ° C under argon Stirred mixture of two-gas methane (100 liters) and methanol (50 ml) 1. 6 stilbyl_2,3_diargyrene (winter methylhexahydro_ python-l-yl) -1Η-indry ( D10, 2.0 g, 0.0077 mol) mixture, benzyl trimethyltribromoammonium (3.14 g, 0.0081 mol) in portions for more than 20 minutes. Allow this mixture to warm to room temperature for more than 1 hour , Then concentrated in true sludge and the residue was dissolved in methane (150 ml), washed with water (150 ml), dried (Na2S〇4) and concentrated in vacuo to obtain a beige solid This title contains 4 daggers (2.52 g, 97%). 28 This paper size applies to China National Standard (CNS) A4 size (210 × 297 mm) (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Printing Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 B7 V. Invention Description (27) ln imK (250 MHz, CDC13) δ (ppm): 8.06 (s, 1H) ^ 7.34 (s9 1Η), 4.06 (t, 2Η), 3.13 (t, 2Η), 3.07 (brs, 4H), 2 06 (br s, 4H), 2.35 ($, 3H), 2.21 (s, 3H).

說明IS S*溴_2,3·二氟木(‘甲基六氣赴參基)嗓 將存於2Μ溴酸（50毫升）之1-乙醢基-2,3-二氩-5-溴_6-(4-甲基六氫此參1.秦)‘1Η-吲哚（D14，0·60克，1.8毫莫耳） 溶液，於室溫下授拌5日，然後藉由添加固體KiC03驗化， 並以DCM萃取。將萃取物乾燥（Na2S04)，並於真空中濃 縮，獲得棕色固體之本標題化合物（0·31克，58%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 7.24 (s, 1H) * 6.42 (s, 1H)，3·80 (br s，1H)，3·56 (t，2H)，3·01-2·92 (m，6H)，2·59 (br s，4H)，2.35 (s，3H)。 說明16 1·乙睡基_2_3•二氧-5·甲基·6*(4“甲基六氫基弓I 哚 使用類似於說明1S之方法，自1-乙醯基_2,3-二氫-5-溴-6_(4-甲基六氫吡基)-1Η_吲哚(D14)與四甲錫製備得米黃色 固體之標題化合物（63%)。 說明17 2,3-二氟“5-甲基_M4_甲基六氬成蟒+基>1H，弓|嵘 使用類似於說明13之方法，i 1_乙贐基r2,3—二氫4甲基-6-(4_甲基六氫赴讲-1_基)_1沁吲哚(D16)製備得米黃色固醴 之標題化合物（89%)。 29 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐) — (請先閲讀背面之注意事項再填寫本頁)Explain that IS S * bromo_2,3 · difluorowood ('methyl hexagas to ginsyl) will be stored in 1M ethyl bromide (50 ml) of 1-ethylamyl-2,3-diargon-5-bromo _6- (4-methylhexahydro this ginseng 1. Qin) '1 哚 -indole (D14, 0.60 g, 1.8 mmol) solution, stirred at room temperature for 5 days, and then by adding solids KiC03 was assayed and extracted with DCM. The extract was dried (Na2S04) and concentrated in vacuo to obtain the title compound (0.31 g, 58%) as a brown solid. lH NMR (250 MHz, CDC13) δ (ppm): 7.24 (s, 1H) * 6.42 (s, 1H), 3.80 (br s, 1H), 3.56 (t, 2H), 3.01- 2.92 (m, 6H), 2.59 (br s, 4H), 2.35 (s, 3H). Explanation 16 1 · Ethyl-2-_2-dioxo-5 · methyl · 6 * (4 "methylhexahydroxyl I indole using a method similar to that illustrated in 1S, starting from 1-ethynyl_2,3- The title compound (63%) was prepared as a beige solid from dihydro-5-bromo-6_ (4-methylhexahydropyridyl) -1Η-indole (D14) and tetramethyltin. Explanation 17 2,3-Di Fluoride "5-methyl_M4_methylhexaargon + python + group" 1H, bow | 嵘 using a method similar to the description of 13, i 1_ ethyl fluorenyl r2, 3-dihydro 4 methyl-6- (4-Methylhexahydro-1) -based compound prepared from the title compound (89%) of beige indole (D16). 29 This paper is sized to the Chinese National Standard (CNS) A4 (210X297) Mm) — (Please read the notes on the back before filling this page)

509687 經濟部中央標準局員工消費合作社印製 A7 _____ B7 五、發明説明（28 ) ln NMR (250 MHz, CDC13) δ (ppm) ： 6,94 (s51H) » 6.44 (s, 1H)，3·52(t52H)，2·95(t，2H)，2·92·2·86(m，4H) , 2.35(s， 3H)，2，19 (s，3H)。 美 說_18 己醸基-2，S·二氬《6-(各_基六氣此參基己烯基·ιη· 俩 將存於乾DMt (15毫升）之經攪拌ί-乙醯基-2,3-二氫-5-瘓_6·(4_肀基六氫吡讲·1_基)-iH-研嗓（D14，600毫克，1.8 毫莫耳）懸浮液，以乙烯基三丁基錫（0.78毫升* 2.7毫莫 耳）處理，並藉由通入鼓泡氬氣除氣20分鐘，然後將三乙 胺（0.50毫升，3,6毫莫耳）和肆(三苯膦你(〇) (200毫克) 加入，並於氬氣下1O0°C時加熱此混合物7小#時。使此混合 物冷卻，以EtOH( 150毫升)#釋，然後以0.5M HC1酸(2x100 毫升）萃取。藉由添加阗艘反2€：〇3驗化該酸萃取物，然後 以DCM (2x100毫升）萃取，並將萃取物乾操（Na2S〇4) 且於真空中濃縮，獲得米黃色固體之標題化合物（480毫 克，95%> 〇 % NMR (250 MHz，CDCb) δ (ppm) : 7·99 (s，1H)，7·31 (s， 1Η)，5.5¾(<ki，lH)，5·Η(dd，1Η)，4·05(UH)，3· 14(t，2¾)， 3·02-2·94 (m，4Η)，2·57φΓ s，4Η) * 2·35 (s，3Η)，2·22 (s，iH)-辑明妗 二IL_M‘甲基六氬硃蟒基6烯基 將存於乙酵（2S毫升）之經攪拌1-乙醯基-2,3-二氫-6“(4· 甲基六氫此4·1-基)_5·6烯基-1Η-吲哚（D18，250毫克， 30 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） ----------装II (請先閱讀背面之注意事項再填頁) 訂 經濟部中央標準局員工消費合作社印製 509687 A7 ___B7 五、發明説明（3 ) 9.0毫莫耳）溶液，以10%NaOH溶液（45毫升）處理，藉 由通入鼓泡氬氣除氣15分鐘，然後於回流下加熱7小時· 使此混合物冷卻，於真空中溧縮至约40毫升饉積，然後並 以DCM萃取办將萃取物乾燥（Na2S04)且於真空中濃維， 獲得棕色固饉之揉起化合物（Π0毫克4 80%)❹ lH m/EH (250 MHz, CDC13) δ (pjpm) ： 730 (s, 1H) ^ 6,98 (dd, 1H>，6·38 (s，1H)，5.49(dd，1H)，5Λ1 (賊 1H)，3·81 (brs， 2Hp 3:56 (t，2H)，2.99 (UH)，2.96-2.90 (m，4H)，2.56 (br s，4H) , 2·35 (s，3H)。 說明20 1- 6龜基_2,3·二氬·5·乙基4(4-甲基六氬毗嵴小基>_1H， 嗓 . 將存於乙醇（100毫升）之經攪拌μ乙醯基-2,3-二氫-6-(4-甲基六氮4b讲-1-基)-5_乙歸基_111-«5丨碌（£)18，4()0毫克， L4毫莫耳）溶液，於大氣壓力和溫度下在⑽0/〇 pd_c (1〇〇 毫克）上進行氫化24小時❶經由通過梦藻土過濾以移除該 催化劑，並將該濾液於真空中濃縮，獲得杀黃色固艎之標 題化合物（380毫克，94%)。 H NMR (250 MHz, CDC13) δ (ppm) ： 8.05 (s, 1¾) 5 7.03 ($, 1H)，4.03<t，2H)，3.13<t，2H)，l96-2.90、(m，4H) , 2.65(q， 2H) ★ 157 (brs，4H)，2.35<s，3H)，2,20 (s，》H)，1.21 (t，3H) 〇 說明21 2,3_二氣_s«乙基各(4_甲基六氬此嵴私瓜為嗓 使用類似於說明13之方法，自1-乙鏟基_2,3_二氫-5·乙基· 31 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)509687 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 _____ B7 V. Description of the invention (28) ln NMR (250 MHz, CDC13) δ (ppm): 6,94 (s51H) »6.44 (s, 1H), 3. · 52 (t52H), 2.95 (t, 2H), 2.92 · 2 · 86 (m, 4H), 2.35 (s, 3H), 2,19 (s, 3H). Mei said _18 Hexyl-2, S · Diargon "6- (Ethyl-Hexyl-6-Gashenylhexenyl · ιη · Both will be stored in dry DMt (15 ml) with stirring ί-ethyl- 2,3-dihydro-5-pyridine_6 · (4_fluorenylhexahydropyridine · 1_yl) -iH-Gar (D14,600 mg, 1.8 mmol) suspension with vinyl tris Treated with butyltin (0.78 ml * 2.7 mmol) and degassed by bubbling argon gas for 20 minutes, then triethylamine (0.50 ml, 3,6 mmol) and triphenylphosphine (triphenylphosphine you ( 〇) (200 mg) was added and the mixture was heated for 7 hours at 100 ° C under argon. The mixture was cooled, released with EtOH (150 ml), and then extracted with 0.5M HC1 acid (2 x 100 ml). The acid extract was assayed by adding a 阗 2 反: 〇3, then extracted with DCM (2x100 ml), and the extract was dried (Na2S〇4) and concentrated in vacuo to obtain a beige solid. Title compound (480 mg, 95% > 0% NMR (250 MHz, CDCb) δ (ppm): 7.99 (s, 1H), 7.31 (s, 1Η), 5.5¾ (< ki, 1H ), 5.Η (dd, 1Η), 4.05 (UH), 3.14 (t, 2¾), 3.02-2 · 94 (m, 4Η), 2.57φΓ s, 4Η) * 2 · 35 (s, 3Η), 2 · 22 (s, iH) -Compilation of di-IL_M 'methyl hexaarginyl 6 alkenyl will be stored in acetic acid (2S ml) after stirring 1-ethyl Fluorenyl-2,3-dihydro-6 "(4 · methylhexahydro this 4 · 1-yl) _5 · 6alkenyl-1 fluorene-indole (D18, 250 mg, 30 paper size applies to Chinese national standard (CNS) Α4 specification (210X297 mm) ---------- Pack II (please read the notes on the back before filling in the page) Order printed by the Central Consumers Bureau of the Ministry of Economic Affairs Consumer Cooperatives 509687 A7 ___B7 V. Description of the invention (3) 9.0 millimolar) solution, treated with 10% NaOH solution (45 ml), degassed by bubbling argon gas for 15 minutes, and then heated under reflux for 7 hours. It was condensed to about 40 ml in vacuo, and the extract was dried (Na2S04) with DCM extraction and concentrated in vacuo to obtain a brown solid compound (Π0 mg 4 80%) ❹ lH m / EH (250 MHz, CDC13) δ (pjpm): 730 (s, 1H) ^ 6,98 (dd, 1H >), 6.38 (s, 1H), 5.49 (dd, 1H), 5Λ1 (thief 1H), 3.81 (brs, 2Hp 3:56 (t, 2H), 2.99 (UH), 2.96-2.90 (m, 4H), 2.56 (br s, 4H), 2.35 (s, 3H). Description 20 1- 6 Turtleyl _2,3 · Diargon · 5 · Ethyl 4 (4-methylhexaargylpyridyl)> 1H, wheeze. Stir in ethyl acetate (100 ml) μ 乙Fluorenyl-2,3-dihydro-6- (4-methylhexaazine 4b-l-yl) -5_ethylhydratyl_111- «5 丨 (£) 18,4 () 0 mg, L4 mmol) solution, hydrogenated at ⑽0 / 〇pd_c (100 mg) at atmospheric pressure and temperature for 24 hours, filtered through diatomite to remove the catalyst, and the filtrate was concentrated in vacuo The title compound (380 mg, 94%) was obtained. H NMR (250 MHz, CDC13) δ (ppm): 8.05 (s, 1¾) 5 7.03 ($, 1H), 4.03 < t, 2H), 3.13 < t, 2H), l96-2.90, (m, 4H), 2.65 (q, 2H) ★ 157 (brs, 4H), 2.35 < s, 3H), 2,20 (s, >> H), 1.21 (t, 3H) 〇 Explanation 21 2,3_ two gas _s «Ethyl (4_methylhexaargine) This method is similar to the method in Note 13, since 1-ethoxy-2-, 3_dihydro-5 · ethyl · 31 paper size Applicable Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)

509687 經濟部中央標準局員工消費合作社印製 A7 ___B7 五、發明説明（30 ) 6-(4-甲基六氫吡嵴4-基)-1Η-吲哚(D20)製備得米黃色固體 之標題化合物（94%) 〇 4 NMR (250 MHz，CDC13) δ· (ppin&gt;: 6.99私，1H)，6.49 (s, 1H)，3.53(t，2H)，2.97(t，2H)，2·90·2鉑細，4H) , 2.59(¾ 2H)，2·54 (br s，4H)，2·35 (s, 3H)，1.19 (t，3H)。 說明22 1，乙應基-2,3_二冬-6*(4·甲基六氧4b _·1·基三敦甲基· 1Η-喵哚 將存於乾DMF (16毫升）和甲笨（1〇毫升）之經攪拌^ 乙醯基-5-溴-2,3-二氫·6_(4-甲基六氫此讲·1·基)丨蜂 (D14,500毫克，1·5亳莫耳）、三氟醋酸鉀（410毫克， 2·7毫莫耳）以及块化亞銅(1)(572毫克，3·(Γ毫莫耳）混合 物，使用迪安和斯塔克頭閘甲笨/水，於氬氣下130。(：時加 熱0·5小時〇將迪安和斯塔克頭置換戒濃縮器，並將該混合 物於155艺時加熱34小時，然後另將三氟醋酸鉀（41〇毫 克）及碘化亞銅①（570毫克）加入，並於155°C時持績加 熱3小時。使該反應混合物冷卻，然後以豨氨溶液（200毫 升）和DCM (150毫升)處理，充分搖晃，然後並通過矽 藻土塞管過濾。將有機層分離，乾燥（Na2S04)並於真空 中濃縮·將殘餘物藉由層析術於鹼性氧化鋁上，以己酸乙 酯溶析而純化，釀得米黃色固體之標題化合物（63%)。 i NMR (250 MHi，Ct&gt;Cl3) δ (_m) : 8·2$ (s—lH)，7·40 (s， 1Η)，4.10 (t，2H)，3.18 汰2«)，2.98-2.92(m，4H)，2.56(br s，4H)，2·35 {s，3H)，2.24 (s，3H)。 32 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） (請先閲讀背面之注意事項再填寫本頁) ,ΤΓ 509687 A7 B7 五、發明説明（31 ) 說明23 2,3_二氣甲基六氬遞蟒_1-基&gt;_义三氟f基-1IMI哚 將存於2MHC1酸（初毫升）和乙醇（25毫升）之1-乙醢 基4,3-二氧各(4“甲基六氩吡蟒·μ基&gt;5_三氟甲基# (D22,260毫克，1·ί毫莫耳）溶液係持在室溫下7曰，然 後於真空中濃縮至约25毫升艟積。將水性殘餘物以固谶 K2C〇3鳋化，然後以ΐχ：Μ萃取，並將萃取物乾燥（Na2S04&gt; 且於真空中濃縮，獲得米|色固體之標題化合物（300毫 克，91%)。 lU NMR (250 MHz, CDC13) δ &lt;ppm) ： 7.30 (s, 1H) » 6.57 (s, 1H)，4·01 (br UH)，3·63 (UH)，3.01 (t，2H)，2.92-2.85 (m， 4H)，2.54 (br s，4H)，2·34 (s，3H)。 # 說明24 咬-4·基)萘-1_基乙酸 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 將存於1&gt;二甲氧乙烷（50毫升）之4-溴萘_1_基乙酸（1 克，3·78毫莫寻，有機化學期刊，1951，16，1588)，以 吡啶冰基硼酸（465毫龙，毫莫耳）、碳酸氫納（952 毫克，1L3毫莫耳）及水（1〇毫升）處理”將氩氣流鼓泡 通入該混合物中1S分雄，然後將肆(三苯膦)la(〇) (200毫 先，0.17毫莫耳）加入，聲將此毖合物於回流下加熱1»小 時-然蟓將此洗合物於真空中濃縮至膠，其係經2M氩氧4 鈉溶狹和二氣甲烷之間進行分配。將水層分離，藉由添加 水性碳酸鉀溶液調整至pH 7，並以二氣甲烷萃取。將二氣 甲烷萃取物乾燥&lt;Na2S04)且於真空中濃縮，獲得標題牝 33 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 . ._ B7 五、發明説明（32 ) 合物，其係自醚中結晶出成針狀师210-215°C (465毫克， 46%) 〇 lB NMR (250 MHz, CDG13) δ (ppm) ： 8.55 (d, 2H) &gt; 8.0 (d5 1H)，7·7 (&lt;UH)，7·5·7·3 (叫 5H)，7.2 (41H)，6.1 伽s，1H)， 4.0(s，2H)， 說明25 5·(此啶《4·基 &gt;秦_1_基乙醮 使用類似於說明24之方法，自5_溴萘4-基乙酸（涞_化學 學會通報，1968，7，2957)與吡咬4-基硼酸製備得榡題化 合物。 lR NMR (250 MHz? CDC13) δ (ppm) ： 8.72 (d, 2H) ^ 8.13 (d, 1H)，7.76(4 1H)，7.60(11H)，7.40-7,50 (m:3H)，7.44(d， 2H)，4.12 ($，2ri)。 說明26 峻#_6_基異氰酸酯 使用類似於說明1之方法，自6_喹琳羧酸激備得標題化合 物。 lH NMR (250 MHz, CDG13) δ (ppm) ： 8.89 (dd, 1H) ^ 8.13-8·06 (m，2H)，152 (d，1H)，7.48-7.41 (m，2H)。 說明27 M4-甲基六氬此嵴-1-基&gt;_1_硝基笨 將K2C03 (52.5克，0385毫莫耳）和雙氣乙基甲胺鹽酸鹽 (31·4克，0·16莫耳）加至存於2-丁醇（500毫升）之3-硝基苯胺（15.0克，0.11莫耳）溶液。於氬氣下伴隨攪拌 34 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） (請先閲讀背面之注意事項再填寫本頁)509687 Printed A7 _B7 printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (30) 6- (4-methylhexahydropyridine 4-yl) -1Η-indole (D20) The title was obtained as a beige solid Compound (94%) 〇4 NMR (250 MHz, CDC13) δ · (ppin &gt;: 6.99 Å, 1H), 6.49 (s, 1H), 3.53 (t, 2H), 2.97 (t, 2H), 2.90 • 2 platinum fine, 4H), 2.59 (¾ 2H), 2.54 (br s, 4H), 2.35 (s, 3H), 1.19 (t, 3H). Note 22 1, Ethyl-2,3_didong-6 * (4 · methylhexaoxo 4b -1 · yltridenylmethyl · 1Η-Meline will be stored in dry DMF (16 ml) and formazan Stupid (10 ml) ^ Ethyl-5-bromo-2,3-dihydro · 6- (4-methylhexahydro this · 1 · yl) 丨 bee (D14,500 mg, 1 · 5 亳 Mol), potassium trifluoroacetate (410 mg, 2.7 mmol), and a mixture of cuprous (1) (572 mg, 3 · (Γmmol)) using Dean and Stark The head brake was stupid / water, and heated under argon for 130 hours. (: 0.5 hour heating, 0. Dean and Stark head replacement or concentrator, and the mixture was heated at 155 hours for 34 hours, and then another Potassium trifluoroacetate (41 mg) and cuprous iodide ① (570 mg) were added and heated for 3 hours at 155 ° C. The reaction mixture was cooled, and then the ammonia solution (200 ml) and DCM were added. (150 ml), shake well, and then filter through a celite plug. The organic layer was separated, dried (Na2S04) and concentrated in vacuo. The residue was chromatographed over basic alumina to Ethyl hexanoate was eluted and purified to obtain the standard of beige solid. The title compound (63%). I NMR (250 MHi, Ct> Cl3) δ (_m): 8. 2 $ (s-1H), 7.40 (s, 1Η), 4.10 (t, 2H), 3.18 2 «), 2.98-2.92 (m, 4H), 2.56 (br s, 4H), 2.35 (s, 3H), 2.24 (s, 3H). 32 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) (Please read the precautions on the back before filling out this page), ΤΓ 509687 A7 B7 V. Description of the invention (31) Description 23 2,3_Digas methylhexagonal python_1-based &gt; _Sense trifluorof-based-1IMI indole will be stored in 2MHC1 acid (initial ml) and ethanol (25 ml) of 1-ethylenyl 4,3-dioxo each (4 "methyl hexapyrazine · μ A base &gt; 5_trifluoromethyl # (D22,260 mg, 1 · L mmol) solution was kept at room temperature for 7 days, and then concentrated in vacuo to about 25 ml of volume. The aqueous residue was mixed with K2CO3 was solidified, then extracted with χ: M, and the extract was dried (Na2S04> and concentrated in vacuo to obtain the title compound (300 mg, 91%) as a beige solid. 1U NMR (250 MHz , CDC13) δ &lt; ppm): 7.30 (s, 1H) »6.57 (s, 1H), 4.01 (br UH), 3.63 (UH), 3.01 (t, 2H), 2.92-2.85 (m, 4H), 2.54 (br s, 4H), 2.34 (s, 3H). # Description24 Bite-4 · Base) Naphthalene-1_acetic acid Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling out this page) Will be stored in 1 &gt; dimethoxyethane (50 Ml) of 4-bromonaphthalene-1-ylacetic acid (1 g, 3.78 mmol, Journal of Organic Chemistry, 1951, 16, 1588), pyridyl glacial boric acid (465 mmol, mmol), carbonic acid Sodium hydrogen (952 mg, 1 L3 mmol) and water (10 ml) were bubbled through an argon stream into the mixture, 1S male, and then (triphenylphosphine) la (〇) (200 mmol) (0.17 mmol), and the mixture was heated under reflux for 1 »hours-then the washing compound was concentrated in vacuo to a gum, which was dissolved in 2M argon 4 sodium and digas methane. Partition between. The aqueous layer was separated, adjusted to pH 7 by the addition of an aqueous potassium carbonate solution, and extracted with digas methane. The digas methane extract was dried <Na2S04) and concentrated in vacuo to give the title 牝 33 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 509687 A7 . ._ B7 V. Description of the invention (32) Compound, which is crystallized from ether into needles 210-215 ° C (465 mg, 46%) 〇lB NMR (250 MHz, CDG13) δ (ppm) : 8.55 (d, 2H) &gt; 8.0 (d5 1H), 7 · 7 (&lt; UH), 7 · 5 · 7 · 3 (called 5H), 7.2 (41H), 6.1 gas, 1H), 4.0 ( s, 2H), explanation 25 5 · (This pyridine "4-yl group" Qin_1_ylacetamidine is used in a similar way to explanation 24, from 5-bromonaphthalene 4-ylacetic acid (涞 _Chemical Society Bulletin, 1968 , 7, 2957) and pyridine 4-ylboronic acid to prepare the title compound. LR NMR (250 MHz? CDC13) δ (ppm): 8.72 (d, 2H) ^ 8.13 (d, 1H), 7.76 (4 1H) , 7.60 (11H), 7.40-7,50 (m: 3H), 7.44 (d, 2H), 4.12 ($, 2ri). Note 26 Jun # _6_yl isocyanate uses a method similar to that in Note 1, since 6_ Quinine carboxylic acid prepared the title compound. LH NMR (250 MHz, CDG13) δ (ppm): 8.89 (dd, 1H) ^ 8.13-8 · 06 (m, 2H), 152 (d, 1H), 7.48- 7.41 (m, 2H). Description 27 M4-methylhexaarginyl-1-yl group> _1_nitrobenzyl K2C03 (52.5 g, 0385 mmol) and digas ethyl methylamine hydrochloride ( 31.4 g, 0.16 mol) added to 2-butanol (500 ml) of 3-nitroaniline (15.0 g, 0.11 mole). Stirring under argon 34 This paper size applies to Chinese National Standard (CNS) Α4 size (210 × 297 mm) (Please read the precautions on the back before filling this page)

經濟部中央標準局員工消費合作社印製 509687 A7 B7 五、發明説明（33 ) 對該反應混合物進行齒流18小時，然後將更多的雙氣〇基 甲胺鹽酸鹽（17.5克，0.09莫耳）及1^0)3 (25.0克，0·18 莫耳）加入，並嫌衊回流中知熬24小時。於真空中移除2-丁酵，並將殘餘物於ΗζΟ (3Θ0奄升）和CH2C12 (300毫升） 間進行分配。蔣CHiCl2分離，並將水相以CH2C12 (3x200 毫升）再萃取。组合有機相，乾燥（Na2S04)並於真空中 濃縮，破得撥色油，其可經由管柱廣析術，於發石凝膠上 a (M%MeOH/dH2CV溶析而純化❶標題化合物為橙色油ο 4 NMR (250 MHz, CDC13) δ (ppm) : 7.72 (d，1H)，7·65 (dd， 1H)，7.37(t，1H)，7.19(dd，1H)，3·31 (t，4H)，2.59(t，4H)， 2.37 (s5 3H) 〇 說明28 甲基六氫毗讲_1-基)笨胺 將3.(4·甲基六氫此讲小基)_1-硝基笨（D27，8.10克，0.037 毫莫耳）溶解於EtOH (250毫升）中，並於室溫和壓力下 在10%Pd/C (2克）上進行氫化18小時。濾除催化劑並將 濾液於莫空中濃縮，獲得淺黃色油之標題化合物（6.64克， 95%) 〇 lamJiR(250 MHz, CDCls) δ (ppm) ： 7.04 (t, 1H) » 6.37 (dd, 1H)，6.2&lt;5(d，1H)，6.21 (dd，lH)，3·60(brs，2H)，3· 18(t，4H)， 2·56 (t，4H)，2.34 (s，3H)。 說明2今 7_(φ·甲基六氣此__1_基)竣成 將3_(4_甲基六氫此1井_1‘基)竽胺（D28，6·6克，0·〇35莫耳） 35 本紙張尺度ϊΐ用中關家標準（CNS ) A4J· ( 21GX297公釐) (請先閲讀背面之注意事項再填寫本頁) -- ^1. 509687 A7 B7 五、發明説明“） 經濟部中央標準局員工消費合作社印製 覆以甘油（8毫升，0.1莫耳），並將濃H2S04酸（Ϊ2毫升， 〇·〇97莫砵），伴隨攪拌，逐滴小心加入超過10分鐘❶裝 好空氣濃縮器，將碘（100毫先）加入，並將此反應攪拌於 i〇(TC下加熱3小時，然辣於1501C下4小時。蔣此反應冷 卻並洗入水（250毫升）〇水相以iC2C03鹼化至ρΗ1〇，並 經萃取至Ctt2Cb (3ίχ300毫升）中。組合有機相，乾燥 (Na2iS04)並权真家中濃縮，獲得皓棕色油，其可維由管 柱層析術，於驗性氧化鋁上以2% MeOH/CH2a2溶析而纯 化。標題化合物為黃色固體（4.05克，52%)。 1HNMR(250MHz,GDC13)5 (ppm) ： 8.78 &lt;m? 1H) » 8.0 (dd, 1H&gt;，16 (d，1H)，7.37 (d，1H)，7.33 (dd，1H)，7·19 (dd，1H)， 3.40 (t，4H)，2,63 (t，4H)，2·38 (s，3H) 〇 · 說明30 甲基六氬戒基&gt;1，2,3,4·田氫嗖琳 將7-(4_甲基六氫吨讲小基)tr奎4 (D29，3.71克，0.016莫 耳）溶解於EtOH 〇00毫升）和AcOH (5毫升）中，並在 沖psi和室溫下於5% Pt/C (1.0克）上進行氫化84小時。 濾掉催化劑，真空中移除溶劑，並將殘餘物於Na2C〇3(叫) 和（¾¾間遂行分配將CH2C12分離，乾燥（Na2S04)並 於真空中濃縮，獲桴淺燈/棕色gj體之標題化合物（3及&gt; 克， 95%)- &quot;Η NM^ (2 知 MHz，CDC13) δ (ppm):众 84 (ά,ΪΙί)，6·27 (d《 1H)，6.05(d，1H)，3.5伽s，1H)，3.27(t，2H)，312(t，4H)， 2·秘(t，2H)，2·55 (ΜΗ)，2.33(s，3H)，1·91 (真重峰，2H)。 36 (請先閲讀背面之注意事項再填頁) ,ιτ 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 509687 A7 B7 五、發明説明（35 ) 說明31 7气4-甲基六氟此蟒-1_基)《1-三氟乙龜基-1,2,3,4-四氣凌琳 將三氟醋醵掛（0.67毫升，4潟毫莫耳）逐滴加入冰中冷卻， 氬氣下，存於CH2C12 (30毫升）之經攪拌7&lt;4·甲基六氟说 讲+基)-1，2,3,4_四氫喹琳（D30，1.0克，4.3毫莫耳）溶液 中。於0°C時待經30分鐘後，將此混合物溫至室溫起過30 分鐘，然後以稀NaHC03(aq)洙滌。將CH2C12分離，乾燥 (Na2S04)並於真空中濃縮，獲得黏稠黃色油之標超化合 物（1.42 克，100%)。 4 NMR &lt;250 MHz，CDC13) δ (ppm) : 7·26 (d，1H)，7.06 (4 1Η)，181 (t，2Η)，3·25 (t,4Η)，2·72 (brs，6Η)，2·45 (s，3Η)， 2.05 (JL 重峰，2H)。 · 說明32 6-淡_7-(4- _基六氳基)《1*三象己龜基-l，2,3,4«四氫 峻秦 使用類似於說明14之方法，自7-(4-甲基六氩吡蟒-1•基)-1-三氣乙醯基1，2,3,4，鯓氫喹啉（〇31)製備得標題化合物。 經濟部中央標準局員工消費合作社印製 NMR (250 MHz, CDC13) δ (ppm) ： 7.39 (s, 1H) &gt; 7.26 (s? 1H) » 3.82 (t, 2H) ^ 3.29 (br s5 4H) ^ 2.99 (brs5 4H) ^ 2S2 (br s，2H&gt;，2A2 (s，3H)，2·05 (五重峰，2ΙΪ)。 娓明33 6-溴-7啵4·,基六氳此讲-1-基)·1,2,3,4-田氟峻考 將K2C〇3⑻（0.50克〗3力毫莫耳)加至存於MeOH (30 毫升）之經攪拌6-溴_7-(4_甲基六氫小基)4-三氟乙醯 37 本紙張尺度適用中國國家標準（CNS ) A4規格（21 Οχ297公襲） 509687 A7 B7 五、發明説明（36 ) 經濟部中央標準局員工消費合作社印製 基-1，2,3,4·四氫峻♦ (D32，0·74克’ 1.8毫莫耳）溶液中0 待於室溫下18小時後，在真空中移除MeOH，並將殘餘物 於 CHsCl2 和 10%Na2C〇3(aq)·間進行分配 &lt;^CH2C12 分離， 乾燥（NaAO4)並於真空_濃縮，獲得黃色/棕色國體之標 題化合物（0·55克，98%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 7.10 (s, 1H) t 6.19 (s^ 1H)，3.85 (br s，1H)，3.26 (m，2H&gt;，2·99 (brs，4H) , ：2,67 (t， 2Ki)，2·59 (br s5 4H)，135 (s，3H)，1·89 (五重峰，2H)。 說明34 1_T醮基-23·二氳硝基丨嗛 將存於CH2a2(200毫升）之2,3-二氫硝基4Η-吲哚（16.4 克，100毫莫耳），於室溫下伴隨連績攪拌，a丁醮氣（10.6 克，100毫莫耳）和Et3N (10.1克，100毫莫耳）處理2小 時。然後將此反應連蹟以5NHC1和飽和水性K2C03溶液洗 滌。然後將此反應乾燥（Na2S04)並於真空中濃縮至膠， 其自石油中結晶出針狀物，獲得標題化合物（23.4克， 100%)。 lU NMR (250 MHz, CDC13) δ (ppm) ： 9.0 (s51H) » 7.85 (dd, 1H)，7.25 (d，1H)，4.15 (t，2H)，3.3 &lt;t，，2·4 (t，2H)， 1.8(q，2H)，l.〇(t，3H)。 說明3S 6*被基_2冬二氮-1_ 丁釀;基-1-H-弓I, 於氫大氣50 psi下，該流速時溫度升至60°C，氫氣妓取停 止，將1-丁醢基-2,3,二氫各硝基-1H-吲哚（D34，19.8克， 38 (請先聞讀背面之注意事項再填寫本頁) 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨〇&gt;&lt;297公釐） 509687 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（37 ) 84.4亳莫耳)與存於MeOH (200毫升）中之10%碳（2克） 上鈀攪拌。然後將此反應通過矽藻土過濾，並以熱MeOH 洗滌該矽藻土以確保無產搿殘存。將該瀘液於真空中蒸 發，獲得針狀標題化合物（13·3克，77%)。 lH NMR (250 MHz, CDCI3) δ (ppm) ： 7.5 (s, 1H) ^ 6.85 (4 1H)，iH)，4.9(s，2H)，4 0 (V2H)，2,9(t，2H)，2·4 (t，2H)，L6 (q，2t)，0:95 (t，3H)。 說明36 1· 丁 •基·2,3·二氮 嗓 保持溫度低於5°C下，將溶於水（10毫升）之亞硝酸鈉（U 先，0.016莫耳）溶液遂滴（附加漏斗尖端接觸液面）處理 〇°C下溶於濃H2S04 (3毫升）和水（35毫升〇混合物之經 攪拌 6·胺基-1-T 醯基-2,3-二氫 _1-H-吲嗓(D35,3.G 克，0.015 莫耳）溶液中。在低於3°C時，先將此混合物攪拌另20分 鐘，然後，在其於0°C下逐滴滴至溶於水（10毫升）之碘 化鉀（2f66克，0·016毫莫耳）。可見到輕微起泡並形成暗 橙色懸浮液。邊使其溫至室溫邊將此混合物携秦另1.5小 時。以EtOAc (3χ)萃取該產物，洗滌（Na2S203溶液）有 機相，聲乾燥（Na2S04)，於蒸發t獲得橙色國艨標題化 合物（3·3克，70〇/〇)❶ HNMR(250MHz, CDCl3)6 (ppm) · 8.64 (s, 1H) &gt; 7.32 (dd, 1H)，6‘90(4,1H)，4 04(t，2H)，3,13(UH)，2.39(t，2H)， 1·75 (ύΐ，2Η)，l.€2(t，3H&gt;〇 說刪37 39 (請先閲讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 509687 A7 B7 V. Description of the invention (33) The reaction mixture was tooth-fluxed for 18 hours, and then more of the two-gas methylamine hydrochloride (17.5 g, 0.09 Mo Ear) and 1 ^ 0) 3 (25.0 g, 0. 18 mol) were added, and it was believed to return for 24 hours. The 2-butanase was removed in vacuo and the residue was partitioned between ΗζΟ (3Θ0 奄 L) and CH2C12 (300 ml). Jiang CHiCl2 was separated, and the aqueous phase was re-extracted with CH2C12 (3x200 mL). The organic phases were combined, dried (Na2S04) and concentrated in vacuo to obtain a discoloring oil, which can be purified by column chromatography on a stone stone gel to elute a (M% MeOH / dH2CV). The title compound is Orange oil 4 NMR (250 MHz, CDC13) δ (ppm): 7.72 (d, 1H), 7.65 (dd, 1H), 7.37 (t, 1H), 7.19 (dd, 1H), 3.31 ( t, 4H), 2.59 (t, 4H), 2.37 (s5 3H) 〇 Description 28 methyl hexahydrobutanyl 1-yl) benzylamine 3. (4 · methyl hexahydron small group) _1- Nitrobenzene (D27, 8.10 g, 0.037 mmol) was dissolved in EtOH (250 ml) and hydrogenated at 10% Pd / C (2 g) at room temperature and pressure for 18 hours. The catalyst was filtered off and the filtrate was concentrated in the air to obtain the title compound (6.64 g, 95%) as a pale yellow oil. LamJiR (250 MHz, CDCls) δ (ppm): 7.04 (t, 1H) »6.37 (dd, 1H ), 6.2 &lt; 5 (d, 1H), 6.21 (dd, 1H), 3.60 (brs, 2H), 3.18 (t, 4H), 2.56 (t, 4H), 2.34 (s, 3H). Explanation 2 Now 7_ (φ · methylhexaqi this __1_ group) is completed to be 3_ (4_methylhexahydro this 1 well_1 ′ group) amidine (D28, 6.6 grams, 0.035 Moore) 35 This paper uses Zhongguanjia Standard (CNS) A4J · (21GX297mm) (Please read the precautions on the back before filling this page)-^ 1. 509687 A7 B7 V. Description of the invention ") Printed with glycerin (8 ml, 0.1 mol) by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, and add concentrated H2S04 acid (Ϊ2 ml, 〇.〇97 砵), with stirring, add carefully dropwise for more than 10 minutes ❶ Install the air concentrator, add iodine (100 milliseconds), and stir the reaction at i0 (3 hours at TC, then spicy at 1501C for 4 hours. The reaction was cooled and washed with water (250 ml). The aqueous phase was alkalized to ρC10 with iC2C03, and extracted into Ctt2Cb (3 × 300 ml). The organic phase was combined, dried (Na2iS04) and concentrated in Quanzhen's home to obtain a halo brown oil, which can be maintained by column chromatography. Purified on analytical alumina with 2% MeOH / CH2a2. The title compound was a yellow solid (4.05 g, 52%). 1HNMR (250 MHz, GDC13) 5 (ppm) : 8.78 &lt; m? 1H) »8.0 (dd, 1H), 16 (d, 1H), 7.37 (d, 1H), 7.33 (dd, 1H), 7.19 (dd, 1H), 3.40 (t, 4H), 2,63 (t, 4H), 2.38 (s, 3H) 〇 · Description 30 methyl hexaarginyl group> 1, 2, 3, 4 Methylhexyl hydrochloride) Tr 4 (D29, 3.71 g, 0.016 mole) was dissolved in EtOH (00 ml) and AcOH (5 ml), and was washed at 5% Pt / C at room temperature under psi and room temperature. (1.0 g) was subjected to hydrogenation for 84 hours. The catalyst was filtered off, the solvent was removed in vacuo, and the residue was partitioned between Na2CO3 (called) and (¾¾). The CH2C12 was separated, dried (Na2S04) and concentrated in vacuo. The title compound (3 and &gt; grams, 95%)-&quot; Η NM ^ (2 known MHz, CDC13) δ (ppm): 84 84 (ά, ΪΙί), 6. · 27 (d <1H), 6.05 (d, 1H), 3.5 gs, 1H), 3.27 (t, 2H), 312 (t, 4H), 2 · (t, 2H), 2.55 (ΜΗ) , 2.33 (s, 3H), 1.91 (True Heavy Peak, 2H). 36 (Please read the precautions on the back before filling in the page), ιτ This paper size applies the Chinese National Standard (CNS) Α4 specification (210X297 mm) ) 509687 A7 B7 3. Description of the invention (35) Description 31 7-gas 4-methylhexafluoro this python-1_yl) "1-trifluoroethamidine-1,2,3,4-Tetragas Linglin hangs trifluoroacetate (0.67 ml, 4 x mol). Add dropwise to ice to cool. Store under CH2C12 (30 ml) under argon. Stir 7 &lt; 4 · methylhexafluoro talk + group) 1,2,3. , 4-tetrahydroquinine (D30, 1.0 g, 4.3 mmol) in solution. After 30 minutes at 0 ° C, the mixture was warmed to room temperature for 30 minutes, and then washed with dilute NaHC03 (aq). The CH2C12 was separated, dried (Na2S04) and concentrated in vacuo to obtain the standard super compound (1.42 g, 100%) as a viscous yellow oil. 4 NMR &lt; 250 MHz, CDC13) δ (ppm): 7.26 (d, 1H), 7.06 (4 1Η), 181 (t, 2Η), 3.25 (t, 4Η), 2.72 (brs , 6Η), 2.45 (s, 3Η), 2.05 (JL heavy peak, 2H). · Instruction 32 6-Tan_7- (4- _Hexafluorenyl) "1 * Three Elephant Hexyl-l, 2,3,4« Tetrahydro Junqin uses a method similar to Instruction 14, since 7- (4-methylhexapyrazine-1 • yl) -1-trifluoroacetamido1,2,3,4, hydroquinoline (〇31) to prepare the title compound. Printed NMR (250 MHz, CDC13) δ (ppm) by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs: 7.39 (s, 1H) &gt; 7.26 (s? 1H) »3.82 (t, 2H) ^ 3.29 (br s5 4H) ^ 2.99 (brs5 4H) ^ 2S2 (br s, 2H &gt;, 2A2 (s, 3H), 2.05 (five-fold peak, 2ΙΪ). 娓 明 33 6-Bromo-7 啵 4 ·, hexahexan -1-yl) · 1,2,3,4-Tian Fujun Kao Add K2C03 (0.50 g〗 3 force mol) to the stirred 6-bromo_7- in MeOH (30 ml) (4-Methylhexahydro small group) 4-trifluoroacetamidine 37 This paper is in accordance with the Chinese National Standard (CNS) A4 (21 0 × 297 public attack) 509687 A7 B7 V. Description of the invention (36) Central Bureau of Standards, Ministry of Economic Affairs Employee Consumer Cooperative Printing Base-1,2,3,4 · Tetrahydrojun (D32, 0.74 g '1.8 mmol) in solution 0 After 18 hours at room temperature, remove MeOH in vacuum The residue was partitioned between CHsCl2 and 10% Na2C03 (aq). <^ CH2C12 was separated, dried (NaAO4) and concentrated under vacuum to obtain the title compound (0.55 g, 98%). lH NMR (250 MHz, CDC13) δ (ppm): 7.10 (s, 1H) t 6.19 (s ^ 1H), 3.85 (br s, 1H), 3.26 (m, 2H &gt;), 2.99 (brs, 4H) ,: 2,67 (t, 2Ki), 2.59 (br s5 4H), 135 (s, 3H), 1.89 (five-fold peak, 2H). Description 34 1_Tamido-23-dioxo丨 嗛 Store 2,3-dihydronitro 4Η-indole (16.4 g, 100 mmol) in CH2a2 (200 ml), and stir at room temperature with continuous agitation (10.6 g, 100 mmol) and Et3N (10.1 g, 100 mmol) for 2 hours. The reaction was then washed with 5NHC1 and saturated aqueous K2C03 solution. The reaction was then dried (Na2S04) and concentrated in vacuo to gel , Which crystallized needles from petroleum to obtain the title compound (23.4 g, 100%). LU NMR (250 MHz, CDC13) δ (ppm): 9.0 (s51H) »7.85 (dd, 1H), 7.25 (d , 1H), 4.15 (t, 2H), 3.3 &lt; t, 2.4 (t, 2H), 1.8 (q, 2H), 1.0 (t, 3H). 3S 6 * 被 基 _2 Winter diazepine-1_ Dingjiu; Ji-1-H-bow I, at 50 psi in hydrogen atmosphere, the temperature rises to 60 ° C at this flow rate, hydrogen hydrogenation is stopped, and 1-butanyl-2,3, dihydro Each nitro-1 H-indole (D34, 19.8 g, 38 (please read the precautions on the back before filling out this page) The size of the paper is applicable to China National Standard (CNS) A4 (2 丨 〇 &gt; &lt; 297 mm) 509687 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (37) 84.4 mol) and 10% carbon (2 g) stored in MeOH (200 ml) are stirred with palladium. Then this reaction Filter through diatomaceous earth and wash the diatomaceous earth with hot MeOH to ensure that no thorium remains. The mash was evaporated in vacuo to obtain the title compound (13 · 3 g, 77%). LH NMR (250 MHz , CDCI3) δ (ppm): 7.5 (s, 1H) ^ 6.85 (4 1H), iH), 4.9 (s, 2H), 4 0 (V2H), 2, 9 (t, 2H), 2.4 · ( t, 2H), L6 (q, 2t), 0:95 (t, 3H). Instructions 36 1 · Ding · Ke · 2,3 · Diatrogen is kept at a temperature lower than 5 ° C, and a solution of sodium nitrite (U first, 0.016 mol) dissolved in water (10 ml) is dripped (additional funnel) The tip is in contact with the liquid surface.) It is dissolved in concentrated H2S04 (3 ml) and water (35 ml) at 0 ° C. 6. Amino-1-T amidino-2,3-dihydro_1-H- Indrum (D35, 3.G g, 0.015 mol) solution. At below 3 ° C, stir this mixture for another 20 minutes, and then dropwise at 0 ° C until it is dissolved in water (10 ml) of potassium iodide (2f66 g, 0.016 mmol). Slight foaming was seen and a dark orange suspension was formed. This mixture was carried for another 1.5 hours while it was allowed to warm to room temperature. EtOAc ( 3χ) The product was extracted, the organic phase was washed (Na2S203 solution), sonicated (Na2S04), and the title compound (3.3 g, 70〇 / 〇) was obtained by evaporation at t. HNMR (250MHz, CDCl3) 6 (ppm ) 8.64 (s, 1H) &gt; 7.32 (dd, 1H), 6'90 (4,1H), 4 04 (t, 2H), 3,13 (UH), 2.39 (t, 2H), 1 · 75 (ύΐ, 2Η), l. € 2 (t, 3H &gt; 〇 said to delete 37 39 (Please read the notes on the back first (Please fill this page again)

、^T 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（38 ) 卞·基_2,3_ 二氮-6-(4fc 咬-4-基弓| 嗓 將溶於二甲氧基乙烷（120毫升）和含Na2C03 (3.85克， 10·4毫莫耳）之水（30毫升）孓1·丁醢基_2,3-二氫-6*硖_1Η· 吲哚（D36，3.2S克，10·4毫莫耳）懸浮液，以氩氣沖洗工 小時。將4_吡啶硼酸（1.3克，10,8毫莫耳）和肆(三苯膦) 鈀(〇) (6如毫克，〇·52毫莫耳）加至混合物中，並將此混合 物於回流下加熱1小時。使此混合物冷卻，真空中蒸發， 並將殘餘物在水和CH2Cl2間進行分配。進一步以CH2CI2 (2χ)萃取該水相，組合有機相，並乾燥（Na2s〇4)，於 蒸發中獲得暗棕色油，其藉由急驟層析術（溶析液5% MeOH/C%Cl2)純化，獲得棕色固體標題化合物（L5克， 54%) 〇 · !H NMR (250MHz? CDCI3) δ &lt;ppm) ： 8.61 (m, 3H) * 7.53 (4 2H) ’ 4.13(t，2H)，3.25(t，2H)，244(t，2H)，l/79(m，2H)， 1.04 (t，3H)。 說明38 1-丁鼸基·2,3-二氫-6-(1-甲基六氬硃蟒冰基碌 經濟部中央標準局員工消費合作社印製 將碘代甲烷（1·6克，1U毫莫耳）加至溶於丙朗（3〇毫升) 之1-丁釀基-2,3-二氫_6,(味啶冰基)-1Η-吲哚（D37，1.5克， 5·63毫莫耳）溶液中，並將此戚合物靜置過夜。過濾獲得 溶於已醇（25¾升）和水（25毫升）之橙色©髋（1.2克）， 並蔣此溶液冷卻至〇t&gt;將麴氧化鈉（06毫克，4·4毫莫 耳）逐份加入該溶液超過5分鐘，並對此混合物攪#另ί〇 分鐘。將2Μ NaOH溶液（16毫升）和水（40毫升）加入 40 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（39 ) 該混合物中，並以CH2C12(2x)萃取該產物，乾燥(Na2S04)， 並於真空中蒸發獲得棕色油（1·〇克）❶然後將該掩溶解於 乙酵（50毫升）並於10% P^i_C (100毫克）上，於50 psi 和50°C卞氩化72小時·過濾並於真空中蒸發，獲得白色固 體標題化合物（710毫克，44%)。 'Η NMR (250MHz, CDC13) δ (ppin) ： 8.19 (s, 1H) · 7.11 (d, 1H) * 6·88 (d，1H)，4 04 (t，2H)，3 J5 (t，2H)，2·96 (brd，2H)， 2.48(m，1H)，2.39(t，2H)，2·31 (s，3H)，2.03(m，2H)，1·82 (m，6H)，1·02 (t，3H)。 說明39 5-淡-2,3_ 二農甲基六氣《it 讲 _4·基嗓 將溴代琥珀醯亞胺（454毫克，2·55毫莫耳）加至溶於醋酸 (20毫升）之經攪拌1_丁醯基_2,3_二氫各(1-甲基六氫毗讲 •4-基)_lH-f丨喷（D38，2.32毫莫耳）溶液中，並將此混合 物於室溫下挽捍過夜。將此混合物以水稀釋並辟固邋K2C03 鹼化。以CH2C12萃界，乾燥（Na2S04)該有機相，並於真 空中蒸發獲得純白固鐶（890毫克）。將—份溶於乙醇（20 毫升）和2MNaOH溶液（30毫升）之國雖（790毫克，U6 毫莫耳），於氬氡下80°C_加熱72小時。以CH2CI2萃取 該產物，乾燥（Na2S04)有機相，並於真空中蒸發獲得橙 色固谶標題仡合物（647毫克，100%)。 lH NMR (250MHz, CDCh) δ (ppm) ： 7.24 (s, 1H) ^ 6.57 &lt;s, 1H)，3.55 (t，2Ή) * 2.99 (m，4H)，2·肽(ά，1H)，2.33 (s，3H) 1 2.10 (m，2H)，1·75 (m，4H” 未觀察到 NH 〇 41 (請先閱讀背面之注意事項再填寫本頁), ^ T This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 509687 A7 B7 V. Description of the invention (38) 卞 · 基 _2,3_ diazo-6- (4fc bite-4-base bow | Throat will dissolve in dimethoxyethane (120 ml) and water (30 ml) containing Na2C03 (3.85 g, 10 · 4 mmol) 孓 1 · butytyl_2,3-dihydro-6 * 硖_1Η · indole (D36, 3.2S grams, 10.4 millimoles) suspension, flushed with argon for 1 hour. 4_pyridineboronic acid (1.3 grams, 10,8 millimoles) and thiophene (triphenylbenzene) Phosphine) Palladium (0) (6 such as mg, 0.52 mmol) was added to the mixture, and the mixture was heated under reflux for 1 hour. The mixture was allowed to cool, evaporated in vacuo, and the residue was taken up in water and Partition between CH2Cl2. The aqueous phase was further extracted with CH2CI2 (2χ), the organic phases were combined, and dried (Na2s〇4) to obtain a dark brown oil during evaporation, which was subjected to flash chromatography (eluent 5% MeOH / C% Cl2) purification to obtain the title compound as a brown solid (L5 g, 54%). .H NMR (250MHz? CDCI3) δ &lt; ppm): 8.61 (m, 3H) * 7.53 (4 2H) '4.13 ( t, 2H), 3.25 (t, 2H), 244 (t, 2H) ), L / 79 (m, 2H), 1.04 (t, 3H). Note 38 1-Dingjiji · 2,3-dihydro-6- (1-methylhexaargine Zhu Mangbing Bingjilu Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs will print iodomethane (1.6 g, 1U mmol) Ear) was added to 1-butynyl-2,3-dihydro-6, (amidinyl) -1 基 -indole (D37, 1.5 g, 5.63 mmol) dissolved in propionol (30 ml) Mol) solution, and the mixture was allowed to stand overnight. The orange © hip (1.2 g) dissolved in hexanol (25¾ liters) and water (25 ml) was filtered, and the solution was cooled to 0 t> Add sodium trioxide (06 mg, 4.4 mmol) to the solution in portions for more than 5 minutes, and stir the mixture for another # 0 minutes. Add 2M NaOH solution (16 ml) and water (40 ml). 40 This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 509687 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (39) The mixture is extracted with CH2C12 (2x) The product was dried (Na2S04) and evaporated in vacuo to obtain a brown oil (1.0 g). The mask was then dissolved in acetic acid (50 mL) and 10% P ^ i_C (100 mg). Argonization at 50 psi and 50 ° C for 72 hours. Filtered and evaporated in vacuo to give the title compound as a white solid (710 mg, 44%). 'Η NMR (250MHz, CDC13) δ (ppin): 8.19 (s, 1H) 7.11 (d, 1H) * 6.88 (d, 1H), 4 04 (t, 2H), 3 J5 (t, 2H), 2.96 (brd, 2H), 2.48 (m, 1H), 2.39 (t, 2H), 2.31 (s, 3H), 2.03 (m, 2H), 1.82 (m, 6H), 1.02 (t, 3H). Explanation 39 5- 淡 -2,3_ 2 Agromethylhexaqi "it Talk_4. Jihu added bromosuccinimide (454 mg, 2.55 mmol) to the stirred 1_butanyl _2,3 dissolved in acetic acid (20 ml) _Dihydrogen (1-methylhexahydropyridine • 4-yl) _lH-f 丨 spray (D38, 2.32 mmol) solution, and the mixture was maintained at room temperature overnight. Diluted with water and solidified K2C03 alkalinization. Extracted with CH2C12, dried (Na2S04) the organic phase, and evaporated in vacuo to obtain pure white solid tincture (890 mg). One part was dissolved in ethanol (20 ml) and 2M NaOH solution. (30 ml) of the country (790 mg, U6 mmol), heated at 80 ° C for 72 hours under argon. The product was extracted with CH2CI2, The organic phase was dried (Na2S04) and evaporated in vacuo to give the title compound (647 mg, 100%) as an orange solid. lH NMR (250MHz, CDCh) δ (ppm): 7.24 (s, 1H) ^ 6.57 &lt; s, 1H), 3.55 (t, 2Ή) * 2.99 (m, 4H), 2. peptide (ά, 1H), 2.33 (s, 3H) 1 2.10 (m, 2H), 1.75 (m, 4H ”No NH observed 〇41 (Please read the precautions on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 ___B7 五、發明説明（4〇 ) 說明40 4-(第三-丁氧基赛基_基&gt; 笨旅 於Ot：下將二-第三-丁基二碳酸酯（4.25毫升，18·5毫莫耳） 加至溶於CH2C12 (50毫升）之經攪拌苯二胺（2·0克；18,5 毫莫耳)溶液中，並將此混合物邊扰林邊溫至室溫16小時。 真空中蒸發，碟得純度80%標題化合物與二-第三丁氧羰基 化合物組成的殘餘物（3.79克，98%)。 (標題化合物）^HNMRpsOMH^CDaOSippnO : 7.13(d， 2H)，6·63 (d，2H)，6·27 (br s51H)，3·50 (br s，2H)，1.50 (s， 9H)〇 說明41 ‘(喵唆各基}苯甲醵 使用類似於說明·2之方法，自4-羧基苯基硼睃和2-溴喊咬 製備標題化合物，獲得淺黃色粉末（35%)。 1HNMR(250MHz,d6DMSO)5 (ppm) ： 12.95 (s, 1H) ^ 8.87 (d，2H)，8·41 (d，2H)，8.00 (4 2H)，7.41 (t51H)。 說明42 4-(嚓啶基)笨基異氧醮酯 使用類似於說明1之方法，自4-(嘧啶-2·基)笨甲酸製備標題 化合物，獲得淺黃色粉末（83%)。 (因不溶於CDC13，未纪錄1HNMR)。 說明43 5_氣，2,3_二氣味笨基联基羰基)甲基六氬蟒士 基丨哚 42 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公羡) &quot; (請先閲讀背面之注意事項再填寫本頁)、 1T This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 509687 A7 ___B7 V. Description of the invention (40) Explanation 40 4- (Third-butoxy Kisaki_Base &gt; Brigade in Ot: add di-third-butyl dicarbonate (4.25 ml, 18.5 mmol) to stirred phenylenediamine dissolved in CH2C12 (50 ml) (2.0 g; 18,5 mmol) and the mixture was allowed to warm to room temperature for 16 hours while disturbing the forest. Evaporation in vacuum gave the title compound with 80% purity and di-tert-butoxycarbonyl Compound residue (3.79 g, 98%). (Title compound) ^ HNMRpsOMH ^ CDaOSippnO: 7.13 (d, 2H), 6.63 (d, 2H), 6.27 (br s51H), 3.50 ( br s, 2H), 1.50 (s, 9H). Explanation 41 '(Meow 唆 each group) benzamidine. The title was prepared from 4-carboxyphenylborane and 2-bromo by using a method similar to that described in 2. Compound to obtain pale yellow powder (35%). 1HNMR (250MHz, d6DMSO) 5 (ppm): 12.95 (s, 1H) ^ 8.87 (d, 2H), 8.41 (d, 2H), 8.00 (4 2H) , 7.41 (t51H). Explanation 42 4- (Pyridine ) Isopropyl isopropyl ester using a method similar to that described in Explanation 1 to prepare the title compound from 4- (pyrimidin-2.yl) benzoic acid to obtain a pale yellow powder (83%). (Because of insoluble in CDC13, 1HNMR is not recorded) 。 Description 43 5_Ga, 2,3_ Diodorant Benzyl Dicarbonylcarbonyl) Methyl Hexapythonyl Benzene 丨 Indole 42 This paper size applies to China National Standard (CNS) Α4 specification (210X297 public envy) &quot; (Please (Read the notes on the back before filling out this page)

509687 A7 _B7 五、發明説明（41 ) 使用類似於實施例4之方法，自5-氣-2,3-二氣甲基&amp; 氫吡4+基MH-51哚和4痛苯胺製備標題化合物，獲得^ 白色粉末（54%)。 4 NMR (250MHz，GDC13) δ φριη) : 7.79 (s，1Η) , 7 6 2Η)，7.23(d，2H)，7·ί5(ΜΗ)，6.37&lt;ΜΗ)，42Η)509687 A7 _B7 V. Description of the Invention (41) Using a method similar to that in Example 4, the title compound was prepared from 5-air-2,3-digasmethyl &amp; To obtain ^ white powder (54%). 4 NMR (250MHz, GDC13) δ φριη): 7.79 (s, 1Η), 7 6 2Η), 7.23 (d, 2H), 7. · 5 (ΜΗ), 6.37 &lt; ΜΗ), 42Η)

3·IS (t，2Η)，3·10 (br s，4Η)，2·61 (brs，4Η) , 2.3&lt;5 (S’3H) I 說明44 ’ N-【4-(4b啶冰基 &gt;萘小基丨已龜胺 將溶於CH2〇2 (10毫升）乙醯氣（0.5毫升，7 0毫莫耳） 逐滴加至（TC下溶於¢:¾¾和三乙胺（1.0毫升，7 1'毫莫 耳）之4-(此啶-4-基)萘_1·基胺（D2，1.5克，6 8毫莫耳)、 溶液中，並將此混合物邊攪拌邊溫至室溫1，小時。以水性 l〇%Na2C〇3洗滌此溶液，乾燥（NazSOO有機相，並於真 空中蒸發，獲得黃色固體標題化合物（1·9克，1〇〇%) '。 H NMR (250MHz, CDC13) δ (ppm) ： 8.73 (d? 2H) » 7.99.7 40 (m，8H)，2.37(s，3H)c 未觀察到 NH。 說明45 队【4，-甲基-1,2,5，卜罇氳曲务4“基條小基1乙鼈鞍 經濟部中央標準局員工消費合作社印製 將埃代甲烷（1.92克，13·6毫莫耳）加至溶於丙_ (5〇毫 升）之Ν·[1(此务4‘基)萘小基]已鎗胺（D44 , I·8克，6 8 毫莫耳）溶液中，並將此涨合物靜置過夜。過綠獲得溶於 乙醇（25毫升）和水（25毫升）之黃色固體（1·2克），冷 卻至〇。(：，並以硼氫化鈉（166毫克，4·4毫莫卑)逐份處 理超埤5分鐘，然後且對此溶液攪拌1小時β將水性ι〇〇/β 43 本紙張尺度適ϋϊί家標準（CNS ) Α4規格（210X297公釐） ' 509687 A7 B7五、發明説明（42 ) 經濟部中央標準局員工消費合作社印製3 · IS (t, 2Η), 3.10 (br s, 4Η), 2.61 (brs, 4Η), 2.3 &lt; 5 (S'3H) I Explanation 44 'N- [4- (4b pyridine ice &Gt; Naphthalene small group hexamethylene chloride will be dissolved in CH2 02 (10 ml) acetamidine (0.5 ml, 70 mmol) dropwise to (soluble in ¢: ¾¾ and triethylamine ( 1.0 ml, 7 1'mole of 4- (this pyridin-4-yl) naphthalene_1-ylamine (D2, 1.5 g, 68 mmol) in solution, and the mixture was stirred while Warm to room temperature for 1 hour. This solution is washed with aqueous 10% Na2CO3, dried (NazSOO organic phase, and evaporated in vacuo to give the title compound (1.9 g, 100%) as a yellow solid. H NMR (250MHz, CDC13) δ (ppm): 8.73 (d? 2H) »7.99.7 40 (m, 8H), 2.37 (s, 3H) c No NH was observed. Description 45 team [4, -methyl -1,2,5, Bu Yi Qu Wu 4 "Baji Xiaoji 1 Yidan Saddle Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Add ED Methane (1.92 g, 13.6 mmol) to the solvent In a solution of N- [1 (4'yl) naphthylnaphthyl] hexylamine (D44, 1.8 g, 68 mmol) in propylene (50 ml) Rested Over green to obtain a yellow solid (1.2 g) dissolved in ethanol (25 ml) and water (25 ml), cooled to 0. (:, and sodium borohydride (166 mg, 4.4 mmol) Treat the solution in portions for 5 minutes, and then stir the solution for 1 hour. Β Water-based 〇〇〇 / β 43 This paper is suitable for household standards (CNS) A4 size (210X297 mm) '509687 A7 B7 V. Description of the invention (42) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs

NaOH (16毫升）和水（40毫升）加入該混合物中，並以 CH2C12葶取該濠物，乾燥(_04),並於真空中蒸發獲 得棕色©體標題化合物（88Q毫克，44% )。 lHmm(250MH^COCh}8^pm) ： ^ 7.86(dd, 1H)，7 J3 (d，1H)，7·53 (m，2H)，7·30(s，1H)，5·74 (m51H)， 3·18 (br d，2H)，2·75 (t，2H)，156 (ni，2H)，2.47 (s，3H)， 2.32 (s，3H)，未觀察到 NH。 說明46 4_&lt;1-甲基六氳啶·4_|&gt;|μΐ·基麽 將溶解於乙醇（50毫升）之N-[4-(l-甲基-1，2,5,6-四氫吡啶 -4-基)萘4-基】&amp;醯胺（D45，800毫克，2·9毫莫耳）溶液， 在50 psi和50°C下於1〇°/❶Pd-C上進行氫化192小時。通過 矽藻土過濾，並將蒸發所得濾液，於蒸發時獲得白色固體 (683毫克）。將固體溶解於乙醇（10毫升)和水性2MNaOH (16毫升）中，旅於氬氣下回流中加熱72小時〇肩:此混合 物以0¾¾萃取，乾燥（Na2S〇4)有機相，並於真空中蒸 發，獲得橙色油標颯化合物（520毫克，76%)。 1HNMR(250MHz, CDCl3)6(ppm) ： 8.06 (dd, 1H) » 7.87 (dd, 1H)，7·53-7·40(ιη，2Η)，7.22(d，1H)，6J8(d，1H)，4.06 (d， 1H)，3· 19 (m，1H)，3·04 (br d，2H)，2.36 (s，3H)，2.20 (m，2H)， 1.92 (m, 4H) ° 說明47 本胺基苯基 甲基噚崚 將2_甲基4-(4-頌基苯基)嘮唑〇·70克，8.2毫莫耳，雜環 44NaOH (16 ml) and water (40 ml) were added to the mixture, and the mixture was extracted with CH2C12, dried (_04), and evaporated in vacuo to obtain the title compound (88Q mg, 44%) in brown. lHmm (250MH ^ COCh) 8 ^ pm): ^ 7.86 (dd, 1H), 7 J3 (d, 1H), 7.53 (m, 2H), 7.30 (s, 1H), 5.74 (m51H ), 3.18 (br d, 2H), 2.75 (t, 2H), 156 (ni, 2H), 2.47 (s, 3H), 2.32 (s, 3H), no NH was observed. Explanation 46 4_ &lt; 1-Methylhexamidine · 4_ | &gt; | μΐ · Glyme will be dissolved in ethanol (50 ml) of N- [4- (l-methyl-1,2,5,6-tetram Hydropyridin-4-yl) naphthalene 4-yl] &amp; fluorene (D45, 800 mg, 2.9 mmol) solution, hydrogenated at 10 ° / ❶Pd-C at 50 psi and 50 ° C 192 hours. Filtration through celite and evaporation of the resulting filtrate gave a white solid (683 mg) on evaporation. The solid was dissolved in ethanol (10 ml) and aqueous 2M NaOH (16 ml), heated under reflux under argon for 72 hours. The mixture was extracted with 0¾¾, the organic phase was dried (Na2S04), and vacuumed. Evaporation gave the orange oil standard hydrazone compound (520 mg, 76%). 1HNMR (250MHz, CDCl3) 6 (ppm): 8.06 (dd, 1H) »7.87 (dd, 1H), 7.53-7 · 40 (ιη, 2Η), 7.22 (d, 1H), 6J8 (d, 1H) ), 4.06 (d, 1H), 3.19 (m, 1H), 3.04 (br d, 2H), 2.36 (s, 3H), 2.20 (m, 2H), 1.92 (m, 4H) ° Description 47 Benzoylmethylmethyl hydrazone 2-methyl 4- (4-sonylphenyl) oxazole 0.70 g, 8.2 mmol, heterocyclic 44

------.__.II 舞 — (請先閲讀背面之注意事項再填寫本頁) 訂 4 509687 A7 B7 五、發明説明（43 ) 化學期刊，1981，18,885)和溶於THF( 10毫升）10%破 (0·20克）上鈀混合物於氫大氣壓下攪拌42小時β過濾此 混合物並於真空中濃縮至乾。藉由層析術將殘餘物於矽石 凝膠上以溶於CH2C12之2°/〇 MeOH溶析純化❶镬播黃色粉 末標題化合物（0.92克）《 lR NMR (250 MHz, CDC13) δ (ppm) ： 7.66 (s, 1H) ^ 7.52 (d, 2H)，6·70 (4 2H)，3·73 &lt;s，2H)，2·49 (s，3H)。 說明48 4·(2麵甲基-Λ啶冰基&gt;笨甲酸 使用類似於說明2之方法，自4-溴-2-甲基此啶（有機化學 期刊1985,50·4410)和冬羧基苯基硼酸製備標題化合物， 獲得白色固體（84%)。 · ^NMR (250 MHz, d6DMSO) δ (ppm) ： 8.52 (d, 1H) » 8.03 (d5 2H)，7.80 (4 2H)，7.61 (s，1H)，7.52 (dd，1H)，2.55 (s，3H)， 未觀察到COOH。 說明49 4_(2_甲暴_此啶基)笨联 經濟部中央標準局員工消費合作社印製 ---------- (請先閲讀背面之注意事項再填寫本頁) 使用類似於說明1之方法，自4&lt;2-甲基-Λ啶冰基)苹甲酸 (D48)形成異氰酸酯，然後經由使用NaOH檢性水解，獲 得米黃色固艎胺（31%)。 1HNMR&lt;25〇l^,CIX：i3)5(ppm) ： S,46(d5lH) ^ 7.52-7.45 &lt;m，2H)，7·31 (s，1H)，7·29-7·24 (nUH)，6.80—6·73 (m，2H)， 3.87(v2H)，2,59(s，3H)。 說明 45 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 B7 五、發明説明（44 ) N-(第三-丁氧基擬基&gt;4#笨按 將二_第三·丁基二碳酸酯（2·99克，0.014莫耳）加至溶乾 二氣甲烷（20毫升）之4-块苯胺（3克，0.014莫耳）溶液 中，隨後將催化含董之4·二甲基胺基畎啶加入❹於環境溫 度下將此反應攪拌過夜，然後以水（2x20毫升）洗滌並乾 燥（MgS〇4)^過濾和蒸發，癉得纯白色固碰（1.90克， 43%)。 ^ NMR (250MHz, CDC13) δ (ppm) ： 7.57 (d, 2H) » 7.14 (dy 2H)，6·43 (br，1H)，1·51 (s，9H)。------.__. II 舞 — (Please read the notes on the back before filling this page) Order 4 509687 A7 B7 V. Description of Invention (43) Chemical Journal, 1981, 18,885) and soluble in THF (10 Ml) 10% broken (0.20 g). The palladium mixture was stirred under hydrogen atmosphere for 42 hours. The mixture was filtered and concentrated to dryness in vacuo. The residue was purified by chromatography on silica gel at 2 ° / 〇MeOH in CH2C12 to dissolve the title compound (0.92 g) as a yellow powder. L NMR (250 MHz, CDC13) δ (ppm ): 7.66 (s, 1H) ^ 7.52 (d, 2H), 6.70 (4 2H), 3.73 &lt; s, 2H), 2.49 (s, 3H). Note 48 4 · (2-sided methyl-Λ-pyridinyl-based group)> Stupid formic acid uses a method similar to that in Note 2 from 4-bromo-2-methyl this pyridine (Journal of Organic Chemistry 1985, 50 · 4410) and winter carboxyl The title compound was prepared from phenylboronic acid to obtain a white solid (84%). ^ NMR (250 MHz, d6DMSO) δ (ppm): 8.52 (d, 1H) »8.03 (d5 2H), 7.80 (4 2H), 7.61 ( s, 1H), 7.52 (dd, 1H), 2.55 (s, 3H), no COOH was observed. Note 49 4_ (2_ 甲 暴 _ 此 丁基) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs- --------- (Please read the precautions on the back before filling out this page) Use a method similar to Note 1 to form isocyanate from 4 &lt; 2-methyl-Amidinyl-based) malic acid (D48) Then, it was detected by hydrolysis using NaOH to obtain beige solid amine (31%). 1HNMR &lt; 2501 (CIX: i3) 5 (ppm): S, 46 (d5lH) ^ 7.52-7.45 &lt; m, 2H), 7.31 (s, 1H), 7.29-7 · 24 ( nUH), 6.80-6.73 (m, 2H), 3.87 (v2H), 2,59 (s, 3H). Note 45 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 B7 V. Description of the invention (44) N- (Third-butoxycarbonyl group &gt; 4 # Stupidly add di-third · butyl dicarbonate (2.99 g, 0.014 mol) to 4-block aniline (3 g, 0.014 mol) dissolved in dry digas methane (20 ml) ) In the solution, the catalyst containing dimethylaminopyridine is added to the solution. The reaction is stirred overnight at ambient temperature, then washed with water (2x20 ml) and dried (MgS04). Filtered and evaporated , Obtained pure white solid bump (1.90 g, 43%). ^ NMR (250MHz, CDC13) δ (ppm): 7.57 (d, 2H) »7.14 (dy 2H), 6.43 (br, 1H), 1 · 51 (s, 9H).

說明SI N-(第三•丁氧基羧基)冰(衊巉-2_基&gt; 笨麽 將N-(第三-丁氧基羰基)-4-破苯胺（D50，319毫克，1毫莫 耳）、雙(醮基)一硼（279毫克，1·1毫莫耳）、含DCM之 1，Γ·雙(二笨基膦基)二(環戊二烯 &gt; 亞鐵二氯鈀(II)錯合物(1:1) (24毫克，0.029毫莫耳)和溶於乾DMF (6毫升）之醋酸 鉀（294毫克，3毫莫耳）混合物，於80°C下加熱2+時。 待經冷卻後，將二溴毽唑（328毫克，2毫莫耳）、2M碳 酸鈉（2.5毫升）和含DCM之1，1’_雙(二苯基_基)二(環戊 二烯)亞鐵二氣鈀(Π)錯合物(1:1) (24毫克，〇·〇29毫奠耳） 和溶於乾DMF (6毫升）之醋酸鉀（294毫克，1豪莫卑) 加入，並將此反應於80°C下加熱18小時。待經冷卻本溶液 後，以水（20毫升）稀釋Μ吏用乙酸乙酯萃取(2x2〇毫升）， 随後經Ο乾燥，過濾並於減壓下蒸發，獲得油。將此於 矽石凝膠上，以溶於6烷10%乙酸乙酯溶析進行層析，獲 46 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） — ------------I (請先閲讀背面之注意事項再填寫本頁)Description SI N- (Third-butoxycarboxyl) Ice (Stilb-2-2-yl)> Benben will be N- (third-butoxycarbonyl) -4-anilide (D50, 319 mg, 1 mmol Mol), bis (fluorenyl) -boron (279 mg, 1.1 mmol), 1, Γ · bis (dibenzylphosphino) bis (cyclopentadiene) containing DCM &gt; ferrous dichloride Mixture of palladium (II) complex (1: 1) (24 mg, 0.029 mmol) and potassium acetate (294 mg, 3 mmol) in dry DMF (6 mL), heated at 80 ° C 2+. After cooling, dibromoxazole (328 mg, 2 mmol), 2M sodium carbonate (2.5 ml), and 1,1'_bis (diphenyl_yl) bis ( Cyclopentadiene) Ferrous Digas Palladium (Π) Complex (1: 1) (24 mg, 0.029 mmol) and Potassium Acetate (294 mg, 1 in dry DMF (6 ml)) (Homo Mob) was added and the reaction was heated at 80 ° C for 18 hours. After cooling the solution, it was diluted with water (20 ml) and extracted with ethyl acetate (2 x 20 ml), followed by 0 Dry, filter, and evaporate under reduced pressure to obtain an oil. This was chromatographed on a silica gel with 6% hexane and 10% ethyl acetate. 46 This paper size applies to China National Standard (CNS) A4 (210X297 mm) — ------------ I (Please read the precautions on the back before filling this page)

、1T 509687 A7 B7 五、發明説明（45 ) 經濟部中央標準局員工消費合作社印製 得呈油之標題化合物（137毫克，50%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 7.91 (d, 2H) » 7.82 (d； 1H)，7·48 (d，2H)，7.27 (d，Ilf)，6.62 (br，1H)，1 ·54 (s，9H)。 說明S24-(噱巉-2_基&gt; 笨胺 將溶於_^氣甲烧（2毫升）和三氣酷酸（〇·ι毫升）之1^-(第 二&quot;·丁氧基魏基碟+2-基)苯胺（D51，122毫克，0.44 毫莫耳）溶液，於環境溫度下加熱18小時，然後並將水（20 毫升）加入。以二氣甲烷（2x10毫升）萃取水相，並將該 萃取物以10%水性碳酸氫鈉（2x10牽升）洗滌，然後乾燁 (MgS04)並於減壓下蒸發，獲得淡黃色油，其經靜置雨 固化（70毫克，90%)。 · !H NMR (250 MHz, CDCi3) δ (ppm) ： 7.76 (m5 3H) ^ 7.20 (m, 3H)，6.72 (d，2H)，3.90 (br s5 2H)。 說明S34_(異春#洛基}苯甲酸 使用類似於說明2之方法，自4_羧基苯基硼酸和4_溴異喹 淋製輪標題化合物，獲得純白色固體（58%)。 ^NMR (250MHz, d^DMSO) δ (ppm) ： 13.15(brs51H)» 9.39 (s，1H)，$·49 (s，1H)，8·25 (4 1H)，8·13 (d，2H) , 7·90·7.67 (m，5H)办 說明S44-{異喳琳-4·基}笨基異氟酸癩 像用類似於說明1之方洚，自4_(異喹4M-基)笨甲竣（D53) 47 (請先閱讀背面之注意事項再填寫本頁)1T 509687 A7 B7 V. Description of the invention (45) The title compound (137 mg, 50%) was produced as an oil by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. lH NMR (250MHz, CDC13) δ (ppm): 7.91 (d, 2H) »7.82 (d; 1H), 7.48 (d, 2H), 7.27 (d, Ilf), 6.62 (br, 1H), 1 54 (s, 9H). Description S24- (噱 巉 -2_yl &gt; benzylamine will dissolve in ^^ methyl ketone (2 ml) and trigas acid (〇 · ι ml) 1 ^-(second &quot; · butoxy Weichai dish + 2-yl) aniline (D51, 122 mg, 0.44 mmol) solution, heated at ambient temperature for 18 hours, and then added water (20 ml). Extracted water with methane (2 x 10 ml) Phase, and the extract was washed with 10% aqueous sodium bicarbonate (2x10 pull-up), then dried (MgS04) and evaporated under reduced pressure to obtain a pale yellow oil, which was solidified by standing rain (70 mg, 90 %).! H NMR (250 MHz, CDCi3) δ (ppm): 7.76 (m5 3H) ^ 7.20 (m, 3H), 6.72 (d, 2H), 3.90 (br s5 2H). Description S34_ (异 春# 洛基} benzoic acid Using a method similar to Note 2, the title compound was prepared from 4-carboxyphenylboronic acid and 4-bromoisoquine, and a pure white solid (58%) was obtained. NMR (250MHz, d ^ DMSO) ) δ (ppm): 13.15 (brs51H) »9.39 (s, 1H), $ 49 (s, 1H), 8.25 (4 1H), 8.13 (d, 2H), 7.90 · 7.67 ( m, 5H) Office explanation S44- {Isoamidine-4 · yl} Benzo isofluoric acid image is similar to that in explanation 1, since 4_ (iso Quin 4M-based) Ben Jiajun (D53) 47 (Please read the precautions on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（46 ) (請先閱讀背面之注意事項再填 製備標題化合物。異氟酸酯係以其甲苯溶液使用，無需濃 縮成淨化合物。、 1T This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 509687 A7 B7 V. Description of the invention (46) (Please read the notes on the back before filling in to prepare the title compound. Isofluorate is based on it Use toluene solution without concentrating to neat compounds.

說明SS Μ螓番_3-基&gt;苯甲觐 使用類似於說明2之方法，自4,羧基苯基硼焱和3_溴峻琳 製備標題化合物，獲得白色固醴(72%)&lt;» lHNMR(250MHz, (1^80)6^111) ： 13.09(brs9 !H) ^ 9.32 (d，1H)，8·76 (d，1H)，107&lt;田，5H)，7·83 (m，2H)，7·67 (m, 1Η)〇 說明S6 4-(喹來-3-基)笨基奥氰酸酯 使用類似於說明51之方法，自4-(喹琳基)笨甲酸（D55) 製備標題化合物·。異氰酸酯係以其甲苯溶液使用， 無需濃縮成淨化合物。 說明57 4-(喳琳各基)苯甲酸 使用類似於說明2之方法，自4-羧基苯基硼酸和8-溴喹琳 製備標題化合物，獲得白色固體（65%)。 經濟部中央標準局員工消費合作社印製 ^NMR(250MHz,d6DMSO)8(ppm) ： 12.98(brs, 1H) » 8.92 (m51H)，8.46(&lt;UH)，8.06(m，3H)，7.80 (m，4H)，7.60 (m， 1H)*&gt; 說明S8 本(喹琳各基 &gt; 輩基典氟酸癱 使用類似於說明51之方法，自4“(喹#各基)笨申酸〇&gt;57) 48 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（47 ) 製備標題化合物◊異氰酸酯係以其甲苯溶液使用， 無需濃縮成淨化合物。 說明59 3-溴哉卜士甲基4b啶(DS9a&gt;和冬溴-2,表；f基此嚏(DS9l〇 於氧氣下室溫時，將溶於二氣申烷（250毫升）之經挽拌三 溴氧化磷&lt;25克，0.085莫耳），以2,6·二甲基4b啶-N-氧 化物（10克，0.081莫耳）處理，然後於自流下加熱6小時〇 使該混合物冷卻，然後並將攪拌完全之冰/水（400毫升） 緩慢加入，並藉由添加K2C03固徼鹼化之。以二氣甲烷萃 取該水性混合物，並將萃取物乾燥（Na2S04)，且於真空 中濃縮。骖殘餘物藉由層析術於破石凝膠上，以1 : 1乙醚 /60-80汽油溶析，以分離得四種成分。第二成分為黃色油之 3-溴-2,6-二甲基4啶（2.5 克，21%)。Description SS Μ 螓 番 _3-yl> benzamidine The title compound was prepared from 4, carboxyphenylboronium and 3-bromojunlin using a method similar to that described in Example 2 to obtain a white solid (72%) &lt; »LHNMR (250MHz, (1 ^ 80) 6 ^ 111): 13.09 (brs9! H) ^ 9.32 (d, 1H), 8.76 (d, 1H), 107 &lt; Tian, 5H), 7.83 (m , 2H), 7.67 (m, 1Η). S6 4- (Quinyl-3-yl) benzyl cyanocyanate was used in a similar manner to Note 51 from 4- (Quinyl) benzylcarboxylic acid ( D55) Preparation of the title compound. Isocyanate is used as a toluene solution and does not need to be concentrated to a neat compound. Instruction 57 4- (Aristolinyl) benzoic acid Using a method similar to Instruction 2, the title compound was prepared from 4-carboxyphenylboronic acid and 8-bromoquinine to obtain a white solid (65%). Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs NMR (250MHz, d6DMSO) 8 (ppm): 12.98 (brs, 1H) »8.92 (m51H), 8.46 (&lt; UH), 8.06 (m, 3H), 7.80 ( m, 4H), 7.60 (m, 1H) * &gt; Explain S8 (Quinyl groups)> Generic acid fluoric acid paralysis using a method similar to that described in 51, since 4 "(quin # each group) stearic acid 〇 &gt; 57) 48 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 509687 A7 B7 V. Description of the invention (47) Preparation of the title compound ◊ isocyanate is used in its toluene solution, and does not need to be concentrated into a neat compound Description 59 3-Bromobenzyl methyl 4b pyridine (DS9a &gt; and winter bromide-2, table; f based on this (DS910 will be dissolved in dioxane (250 ml) at room temperature under oxygen, Phosphorus tribromide &lt; 25 g, 0.085 mole), treated with 2,6 · dimethyl 4b pyridine-N-oxide (10 g, 0.081 mole), and then heated under autogenous flow for 6 hours. The mixture was cooled, and the fully stirred ice / water (400 ml) was added slowly and basified by adding K2C03. The aqueous mixture was extracted with methane and the extract The extract was dried (Na2S04) and concentrated in vacuo. The residue was chromatographed on a lithotripsy gel and eluted with 1: 1 ether / 60-80 gasoline to separate four components. Second The composition is 3-bromo-2,6-dimethyl4-pyridine (2.5 g, 21%) as a yellow oil.

]H NMR (250 MHz, CD€13) δ (ppm) ： 7.66 (d51H) » 6.86 (4 1H)，2·63 (s，3H)，2·48 (s, 3HP 而第三成分為淺黃色油之4-溴-2,6-二甲基畎啶（1.5克， 12%)。 lR NMR (250 MHz, CDC13)^ (ppm) ： 7.16 (s, 2H) ^ 2.50 (s? 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 6H)〇 說明60 4_(2,6_二甲基_此咬冰基)笨甲酸 使南類似於說明2之方法，自4·溴-2,6-二甲基味啶（¢)5%) 和4-羧基苯基硼酸製備榡題4b合物，獲得白色自髏(76% ) 〇 !HNMR(2501^,(1^80) δ (ppm) ： 8.05 (d52H) ^ 7.86(4 49 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐) &quot; — 509687 A7 B7 五、發明説明（4&amp; ) 2H)，7·42 (s，2H)，2·50 (s，6H)。未觀察到酸性質子。 說明60 4-(2,6-二宇基啶-3-基&gt;苯甲酸 使用類似於說明2之方法，自3·濟二甲基此啶（D59a) 和4-薄基苯基硼酸製備標題化合物，獲得米黃色固體 (76%) 〇 ^NMR (250MHz? d6DMSO) δ (ppm) ： 8.00 (d,2H) ^ 7.52(4 1H)，7·42 (d，2H)，7·18 (d，1H)，2·47 (s，3H)，2,40 (s，3H)。 未觀察到酸性質手。 說明62 4-(2,6-二甲基-4b峻-4_基)笨基異氰酸籬 使用類似於說明1之方法，自4&lt;2,6-二甲基·〇*啶冰基)苯甲 酸（D60)製備標題化合物❶使用異氰酸_之_苯溶液，無 需濃縮成淨化合物。 說明63 4-(2,6-二甲基-此咬_3-基)苯基異氰酸磨 經濟部中央標準局員工消費合作社印製 使用類似於說明1象方法，自4_(2,6·二甲基啶-3-基)輩甲 酸（D61)製備標題化合物。使用美氟酸酯之甲苯溶液，無 需濃縮成淨化合物。 說明64 8-滇-多硝基喳琳 將心溴喹《#逐滴加至攪拌完全之濃氏3〇4 (5毫升）、濃 HN〇3 (10毫升）和發煙_3 (毫升）溶液中，於冰中冷 卻。將此混合物於65ΰς下加熱30小時，然後冷卻並將其二 50 (CNS) Kum ( noxigv^T^ ----〜— 509687 A7 ___B7 五、發明説明（49 ) 入邊挽拌之H20 (350毫升）中❶過濾所形成之沈澱物，以 水洗滌並於真空下乾燥，獲得淡乳黃色固體榡題化合物 (1.10 克，60%)。 lnmm.(25〇mizXOCh)d(ppm) ： 9.17(44 IH)&gt; 9.07(dd, 1H&gt; U6 (4,1Η)，8·20 (d，1Η)，7·74 (dd，1H)❶ 說_ 65 5«硝基笨基喹· 使用類似於說明2之方法，自8-溴-5_硝基全琳(D64)和 笨基硼酸製備標題化合物，獲得橙色/棕色固體（99%)。 i^fMR(250MHz，CDOb) δ (ppm) : 9.11·9.05(ιη，2Η)，7.82 (4 1Η)，7.70-7·63 (m，3Η)，7,59-7.64 (mv3H)。 說m μ 5·联基-8«笨基4琳 使南類似於說明邡之方法，自5-硝基-8·苯基喹啉（Ε&gt;65) 製備標題也合物，獲得橙色/棕色固體（97%)❶ 1HNMR(250MHz,CDGI3)8 (ppm) ： 8.93 (dd? 1H) ^ 8.21 (dd, 1ϋ)，7.76 (dd，1H)，7.66(4 1H)，759-7.32 (tn5 5H)，6.89(d， 1H)，4,23(s，2H)。 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 說明67 f乙癱磨基甲基嶠# 使用類似於說明$之方法，自6_胺基*2·甲基者4和醋酸酐 製備標題化合物，獲得綠色固體（95%)。 ^NMR (250MHz, CDC13) δ (ppm) ： 8.30 &lt;4 1Η) ^ 8.01 (d, 1H)，7.95 (d51H)，7.49 (m，2H)，7·27 (41Ή)，2.72 (s，3H)， 51 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐) 509687 A7 ____B7 五、發明説明（5〇 )] H NMR (250 MHz, CD € 13) δ (ppm): 7.66 (d51H) »6.86 (4 1H), 2.63 (s, 3H), 2.48 (s, 3HP and the third component is light yellow 4-Bromo-2,6-dimethylpyridine (1.5 g, 12%) of oil. LR NMR (250 MHz, CDC13) ^ (ppm): 7.16 (s, 2H) ^ 2.50 (s? Central Ministry of Economic Affairs Printed by the Consumer Bureau of the Standards Bureau (please read the precautions on the back before filling this page) 6H) 〇 Description 60 4_ (2,6_dimethyl_this bite ice base) Benzoic acid is similar to the method in Note 2 , From 4 · bromo-2,6-dimethylamidine (¢) 5%) and 4-carboxyphenylboronic acid to prepare the title 4b complex, a white self-skeleton (76%) 〇! HNMR (2501 ^, (1 ^ 80) δ (ppm): 8.05 (d52H) ^ 7.86 (4 49 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) &quot; — 509687 A7 B7 V. Description of the invention (4 &amp;) 2H), 7.42 (s, 2H), 2.50 (s, 6H). No acidic proton was observed. Explanation 60 4- (2,6-diastildin-3-yl> benzoic acid used The title compound was prepared in a similar manner to that described in Example 2 from 3-dimethyldimethylpyridine (D59a) and 4-thinylphenylboronic acid to obtain a beige solid (76%). NMR (250M) Hz? D6DMSO) δ (ppm): 8.00 (d, 2H) ^ 7.52 (4 1H), 7.42 (d, 2H), 7.18 (d, 1H), 2.47 (s, 3H), 2 , 40 (s, 3H). No acidic hand was observed. Note 62 4- (2,6-dimethyl-4bjun-4_yl) benzyl isocyanate was used in a similar way to Note 1, since 4 &lt; 2,6-dimethyl · 〇 * pyridyl) benzoic acid (D60) to prepare the title compound ❶ using isocyanate _ benzene solution, without the need to concentrate to a neat compound. Explanation 63 4- (2,6- Dimethyl-this bite 3-yl) phenyl isocyanate mill Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, using a method similar to that described in the 1-method, since 4- (2,6 · dimethylpyridin-3-yl ) Formic acid (D61) to prepare the title compound. Toluene solution of meflunate was used without concentration to neat compound. Note 64 8-Dian-Polynitroquinine Add cardiobroquine "# dropwise to the fully stirred concentration 304 (5 ml), concentrated HNO3 (10 ml) and fuming_3 (ml) solution, cooled in ice. This mixture was heated at 65 ° C for 30 hours, then cooled and cooled to 50 ° C. (CNS) Kum (noxigv ^ T ^ ---- ~ — 509687 A7 ___B7 V. Description of the invention (49) The formed precipitate H20 (350 ml) ❶ filtered, washed with water and dried under vacuum to give a pale yellow solid milk Su title compound (1.10 g, 60%). lnmm. (25〇mizXOCh) d (ppm): 9.17 (44 IH) &gt; 9.07 (dd, 1H &gt;) U6 (4,1Η), 8.20 (d, 1Η), 7.74 (dd, 1H) ❶ Say _ 65 5 «nitrobenzylquine · The title compound was prepared from 8-bromo-5_nitroquinolin (D64) and benzylboronic acid using a method similar to Note 2 to obtain an orange / brown solid (99%) I ^ fMR (250MHz, CDOb) δ (ppm): 9.11 · 9.05 (ιη, 2Η), 7.82 (4 1Η), 7.70-7 · 63 (m, 3Η), 7,59-7.64 (mv3H). Say m μ 5 · Byky-8 «Benyl 4 Linden makes the title similar compound from 5-nitro-8 · phenylquinoline (E &gt; 65) similar to the method described in 邡 to obtain an orange / brown solid (97%) ❶HNMR (250MHz, CDGI3) 8 (ppm): 8.93 (dd? 1H) ^ 8.21 (dd, 1,), 7.76 (dd, 1H), 7.66 (4 1H), 759-7.32 (tn5 5H) , 6.89 (d, 1H), 4,23 (s, 2H). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). Description 67 f Ethyl paramethyl # Using a method similar to Instruction $, preparing the title compound from 6-amino * 2.methyl 4 and acetic anhydride to obtain a green solid (95%). NMR (250MHz, CDC13) δ (ppm) 8.30 &lt; 4 1Η) ^ 8.01 (d, 1H), 7.95 (d51H), 7.49 (m, 2H), 7.27 (41Ή), 2.72 (s, 3H), 51 This paper applies the Chinese National Standard (CNS) ) A4 specification (210X297 mm) 509687 A7 ____B7 V. Description of the invention (50)

2.25 (s, 3H) 〇 說明6S 6·按基，&gt;(2·笨基匕烯基&gt;喹_ 將溶於醋睃酐（6毫升）之6-乙醢胺基-2-甲基喹唭（D67， 600毫克，3.0毫莫耳）懸浮液，以笨甲醛（954毫克，9·0 毫莫耳）處理，並將此混合物於120°C下加熱40小時，然 後冷卻並於真空中移除醋酸酐。將殘餘物溶解於2MNaOH (30毫升）和EtOH (10Ό毫升）中，並於回流下伴隨授捍 加熱。待經18小時後，於真空中移除EtOH，並將該殘餘 物以EtOH(3xlOO毫升)萃取。组合有機相，乾燥(Na2s〇4)， 並於真空中濃縮，獲得粗棕色油，其可藉由層析術，於鹼 性氧化鋁上以EtpAc溶析雨純化。獲得棕色固體標題化合 物（210毫克，28%)，部份受到苯甲酵污染。 [H NMR (250MHz, CDC13) δ (ppm) ： 7.91-7.87 (m, 2H)-7‘60-7.56(m，2H)，7.54 (41Η)，7.42-7 28 (m5 5H)，7.15 (d4 1H)，6·89 ，3·96 (s，2H)。 說明70 2-(3,硝基笨氧基 &gt;省鳴 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 將3-硝基酚（2·08克，15毫莫耳2-溴嘧啶（2.38克， 15毫莫耳）和溶於乾pMF無水碳酸鉀&lt;2 76克，20毫莫 耳）之經授拌混合物，於S0°C下加熱4小時。將經+卻之 混合物於真空中濃縮至乾，並將幾餘物於CH2Cii(75毫升） 和水（50毫升）間進行分祝。將有機相分離，以水洗滌， 乾燥（Na2S04)並於真空中濃縮至乾。藉由層析街將殘餘 52 本紙張尺度適用中國國家標準（CMS ) ( 210Χ297公釐） _ 509687 A7 B7 五、發明説明（51 ) 經濟部中央標準局員工消費合作社印製 物於梦石凝膠上以CHiCl2溶析而純化❶單離得淺黃色耠末 標題化合物（1·94克，60%)。 1HN^pt(250MHz,CDa3)8 (ppm) ： 8.60&lt;d,2H) » 8.14 (m, 2H)，t58(m，2H}，7.12(t，lH)。 說明71 3_(嗜咬-2-基氧基)笨麽 將濃HC1 (0·7毫升）加至經攪拌2·&lt;3·端基苯氧基)嘧啶 (D7Q，0.65克，3毫莫耳）和溶於甲酵（3〇毫升）氣化錫 (II) (2.28克，12毫莫耳）混合物中。將此藏合物於回流卞 加熱2小時，冷卻，並於真空中濃縮近乾。將此殘餘物以 OfeCl2 (50毫升）和水（25毫升）處理，並將2Ν NaOH 溶液加入以調整pH至過濾此混合物並將有機相分離， 以水洗滌，乾燥（Na2S04)並於真空中濃縮至乾，獲得黃 色粉末標題化合物（0·50克，89%)。 4 NMR (250 MHz，CDC13) δ (ppm) : 8·55 (d，2Η)，7,19 (t， 1H)，7.02 (t，1H)，6·59·6·51 (m，3H)，3.76 (s，2H)。 說明72 Ν·甲基·‘硝基-N气嘯咬+基&gt; 笨联 將第三，丁氧化鉀（L79克，16毫莫耳）加至經攙拌溶於乾 DMF (25毫升）之甲基_4_端基苯胺（2.20克，14.5毫莫 耳）溶液中。待於寞深下攪拌1小時後，將公溴嘧啶（2·3〇 克，14·5毫莫茸），並將此混合物溫至8(TC6小時，然後 並於家溫下靜置過夜。待將殘餘物於真空中濃縮至乾 將其於CH2CI2 (1〇0毫升）和水（30毫升）間進行分配。 53 (請先閲讀背面之注意事項再填寫本頁)2.25 (s, 3H) 〇 Explanation of 6S 6. Analytical group, &gt; (2. Benzoylalkenyl) &gt; quine 6-acetamido-2-methyl which will be dissolved in acetic anhydride (6 ml) A suspension of quinoxaline (D67, 600 mg, 3.0 mmol) was treated with benzaldehyde (954 mg, 0.9 mmol), and the mixture was heated at 120 ° C for 40 hours, then cooled and vacuumed. Acetic anhydride was removed from the solution. The residue was dissolved in 2M NaOH (30 ml) and EtOH (10 (ml) and heated under reflux with reflux. After 18 hours, the EtOH was removed in vacuo and the residue was removed. The material was extracted with EtOH (3x100 ml). The organic phases were combined, dried (Na2s〇4), and concentrated in vacuo to obtain a crude brown oil, which can be chromatographed over basic alumina with EtpAc Purification. The title compound (210 mg, 28%) was obtained as a brown solid, partially contaminated with benzoate. [H NMR (250MHz, CDC13) δ (ppm): 7.91-7.87 (m, 2H) -7'60-7.56 (m, 2H), 7.54 (41Η), 7.42-7 28 (m5 5H), 7.15 (d4 1H), 6.89, 3.96 (s, 2H). Description 70 2- (3, nitrobenzyloxy) Basic &gt; Staff Consumption Cooperation Printed by Sakusha (please read the precautions on the back before filling out this page). 3-Nitrophenol (2.08 g, 15 mmol. 2-bromopyrimidine (2.38 g, 15 mmol.) And dry pMF anhydrous potassium carbonate (2 76 g, 20 mmol) was heated at S0 ° C for 4 hours. The + + mixture was concentrated to dryness in vacuo, and several residues in CH2Cii (75 ml) and water (50 ml). Separate the organic phase, wash with water, dry (Na2S04) and concentrate to dryness in vacuo. Residue 52 through chromatography street. This paper is suitable for China Standard (CMS) (210 × 297 mm) _ 509687 A7 B7 V. Description of the invention (51) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs on the dream stone gel with CHiCl2 to purify it. End title compound (1.94 g, 60%). 1HN ^ pt (250MHz, CDa3) 8 (ppm): 8.60 &lt; d, 2H) »8.14 (m, 2H), t58 (m, 2H), 7.12 ( t, lH). Explanation 71 3_ (Bite-2-yloxy) benzyl Add concentrated HC1 (0.7 ml) to the stirred 2 &lt; 3 · terminal phenoxy) pyrimidine (D7Q, 0.65 Grams, 3 millimoles) and soluble A yeast (3〇 mL) gasification tin (II) (2.28 g, 12 mmol) to the mixture. The Tibetan compound was heated at reflux for 2 hours, cooled, and concentrated in vacuo to dryness. This residue was treated with OfeCl2 (50 ml) and water (25 ml) and 2N NaOH solution was added to adjust the pH to filter the mixture and the organic phase was separated, washed with water, dried (Na2S04) and concentrated in vacuo To dryness, the title compound was obtained as a yellow powder (0.50 g, 89%). 4 NMR (250 MHz, CDC13) δ (ppm): 8.55 (d, 2Η), 7,19 (t, 1H), 7.02 (t, 1H), 6.59 · 6 · 51 (m, 3H) , 3.76 (s, 2H). Description 72 Ν · methyl · 'nitro-N gas bite + radical> Benlian added the third, potassium butoxide (L79 g, 16 mmol) to dry DMF (25 ml) after mixing Methyl_4_ terminal aniline (2.20 g, 14.5 mmol) in solution. After stirring for 1 hour in the dark, the bromopyrimidine (2.30 g, 14.5 mmol) was warmed, and the mixture was warmed to 8 (TC for 6 hours, and then allowed to stand overnight at home temperature. After the residue was concentrated to dryness in vacuo, it was partitioned between CH2CI2 (100 ml) and water (30 ml). 53 (Please read the precautions on the back before filling this page)

、1T 本紙張尺度適用中國國家榡準（CNS〉Α4規格（210X297公釐） 509687 A7 B7 五、發明説明（52) 將有機相以水洗滌，乾燥（Na2S04)並濃縮至乾於二乙 醚中研磨殘餘物，獲得淺橙黃色粉末標題化合物（1·24克， 37%) - · lR NMR (250 MHz, CDC13) δ (ppm) ： 8.43 (d, 2H) » 8.25 (d, 2H) * 7·56 (4 2H)，6.77 (t, 1H)，3·67 (s，3H)。 說明73 ‘【N.甲基(嚙矣基)廉基1装联 將溶於甲酵（70毫升）和6酸已德（70毫升）之N-甲基-4·硝基-N-(嘧啶-2-基)笨胺（D72，1.30克，5·6毫莫耳）溶 液，以10%碳（0.25克）上鈀處理，並於1大氣壓氫氣下 搖晃48小時。將經過濾之混合物濃縮至乾，並將殘餘物於 二乙鰱中研磨，探得淺棕橙色粉末標題化合物（0.78克， 68%) 〇 lH NMR (250 MHz, CDC13) δ (ppm) ： 8.30 (d? 2H) ^ 7.07 (d, 2H)，6.68 (d，2Ή)，6.48(t，1H)，3·66(brs，2H)，3.45 (s，3H)。 說明74 5-(硃啶冰基 &gt; 萘基胺 經濟部中央標準局員工消費合作社印製 使用類似於說明2之方法，自5-溴小萘基胺（JP 08L51353A2)和4_选啶硼酸製備標題化合物。 ^NMR(250MHz,CDC13)6(ppm) ： 8.75-S.67(m,2H) ^ 7.93 (d，1H&gt;，7.70^7.35 (m，4H)，7.28-7】0(m，2H)，6.85»6.80(m， tH)，4.25(s，2H)。、 1T This paper size is applicable to China National Standards (CNS> A4 specification (210X297mm) 509687 A7 B7 V. Description of the invention (52) Wash the organic phase with water, dry (Na2S04) and concentrate to dry in diethyl ether and grind The residue obtained the title compound as a pale orange-yellow powder (1.24 g, 37%)-· lR NMR (250 MHz, CDC13) δ (ppm): 8.43 (d, 2H) »8.25 (d, 2H) * 7 · 56 (4 2H), 6.77 (t, 1H), 3.67 (s, 3H). Note 73 '[N. Methyl (pyridinyl) imino 1 unit will be dissolved in formazan (70 ml) and 6-Acetyl (70 ml) N-methyl-4 · nitro-N- (pyrimidin-2-yl) benzylamine (D72, 1.30 g, 5.6 mmol) solution with 10% carbon ( 0.25 g), treated with palladium, and shaken under 1 atmosphere of hydrogen for 48 hours. The filtered mixture was concentrated to dryness, and the residue was triturated in diethyl ether to obtain the title compound as a light brown orange powder (0.78 g, 68 %) 〇H NMR (250 MHz, CDC13) δ (ppm): 8.30 (d? 2H) ^ 7.07 (d, 2H), 6.68 (d, 2Ή), 6.48 (t, 1H), 3.66 (brs, 2H), 3.45 (s, 3H). Explanation 74 5- (Cudidine ice-based &gt; Naphthylamine Central Standard Printed by the Bureau's Consumer Cooperative, using a method similar to Note 2, to prepare the title compound from 5-bromo-p-naphthylamine (JP 08L51353A2) and 4-picolinylboronic acid. NMR (250MHz, CDC13) 6 (ppm): 8.75- S.67 (m, 2H) ^ 7.93 (d, 1H &gt;, 7.70 ^ 7.35 (m, 4H), 7.28-7] 0 (m, 2H), 6.85 »6.80 (m, tH), 4.25 (s, 2H ).

說明7S 队掊_(赴啶冰基)萘基丨l瞳胺 54 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 B7 五、發明説明（53 ) 使用類似於說明44之方式，自5-(4啶*4_基)萘-1·基胺（D 74)製備標題化合物。MIT263。 說明76 甲基四氫此势4·基 &gt;萘-1-基丨乙齙联 使用類似於說明45之方式，自Ν-[5+Λ啶冰基)萘4-基J乙 醢胺（D75)製備標題化合物〇 ΜΚΤ281。 說明77 5*(1_甲基六氬赴啶冰基)萘-1-基胺 使用類似於說明46之方式，自N_[5-(l-甲基-1，2,5,6-四氫此 啶冰基)萘-1-基】已醯胺（D 76)製備標題化合物。 lH NMR (250MHz, CDC13) δ (ppm) ： 7.72 (ιη, ΙΗ) * 7.57 &lt;d5 1Η)，7·42 (m，2Η)，7·32 (VlH)，6·78 (&lt;UH)，4· 16 (hrs，2Η)， 3·28 (m，1H)，3·05 (br d，2H)，2.37 (s5 3H)，2.20 (m，2H)， 1.93(m，4H)〇 說明78 Ν-2«(4·硝基笨基&gt; 〇基-三氟乙建胺 將溶於二氣甲烷（J00毫升）之三氟醋酸針（10.6毫升）逐 滴加入&lt;rc時尤經攪拌2,6·二甲基吡啶（II4亳升）和硝墓 苯乙胺鹽酸鹽（15i克，75毫莫耳）溶液中。於氬氣下25 °0：時，將此混合物攪拌過夜，然後並以稀#檬酸（x2)、 蕹水洗鲦，並乾燥（Na2S04)。★機相中之物質獲得淺黃 色固艎標題化合物〇9·04克）。 說明79 7-硝基-1,2,3,4-田氬_2_三氣已瞳基異叆琳 55 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁) 4 、&quot; 經濟部中央標準局員工消費合作社印製 509687 A7 __^_B7 五、發明説明（54 ) 根據G.E.史托克，西面體快報，1996，37，5453之方法， 將Ν-2·(4-硝基苯基)乙基-三氟6斑胺（D78，2.26克，9.15 毫莫耳）和溶於醋酸(10毫升）之低聚甲醛（Ρ·45克，I4·4 毫莫專）和濃H2S04 (15毫升）於25¾卞攪拌20 Φ時。完 成後產得白色固體標題化合物(2.17克）。 !HNMR (250MHz, C〇a3) δ (ppm) ： 8.10 (m5 2H) » 7J8 (t, 1H)，4·92-4·85 (2xs，2H)，3.92 (m，2H)，3.10 (m，2H)。 MH+274 -說明80 7-項基-1,2,3,4-四氬異喳琳 於室溫下，使用溶於10〇/〇水性甲醇(660毫升)之碳酸鉀(46.6 克）溶液水解7-硝基-1，2,3,4-四氫-2-三氟i贐基異喹啉 (打79，！7.2克，63毫莫耳）“與二氣甲烷做成標題化合 物（11克）。 說明81 2-甲基-7-讀基_1，2,3,4-四氬異峻名 根據GM*卡雷拉和D.S.加維，雜環化學期刊，1992，29， 847之方法，於S〇t下，將7-硝基4,2,3,4·四氩異喹啉 (D80，2.08克，11.7毫莫耳），以88%甲酸（3 45毫升） 和37%水性甲醛（5·88毫升）處理2小時。以10%氫氧牝 鉀鹼化，隨後以乙酸乙酯萃取，獲得撥色釀&lt;2.3克）❶藉 由層析術於破石凝膠上以〇_3%甲醇/乙酸乙_，獲得橙色固 艘標題化合物（1.7克）。Mffi93。 說明82 56 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ' (請先閲讀背面之注意事項再填寫本頁)Note 7S team 掊 ((pyridylbenzyl) naphthyl) naphthalenyl 54 l Tylamine 54 This paper size applies to China National Standard (CNS) A4 (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs DESCRIPTION OF THE INVENTION (53) The title compound was prepared from 5- (4pyridine * 4-yl) naphthalene-1 · ylamine (D 74) in a manner similar to that of Instruction 44. MIT263. Explanation 76 Methyltetrahydro this potential 4-yl group> Naphthalene-1-yl 丨 Ethylene coupling is used in a manner similar to Illustration 45, starting from N- [5 + Λ pyridyl) naphthyl 4-ylJ ethylamine ( D75) The title compound OMKT281 was prepared. Note 77 5 * (1-methylhexaarginylpyridyl) naphthalen-1-ylamine is used in a manner similar to Note 46, starting from N_ [5- (l-methyl-1,2,5,6-tetramethyl Hydroxypyridyl) naphthyl-1-yl] hexamide (D 76) prepared the title compound. lH NMR (250MHz, CDC13) δ (ppm): 7.72 (ιη, ΙΗ) * 7.57 &lt; d5 1Η), 7.42 (m, 2Η), 7.32 (VlH), 6.78 (&lt; UH) , 4.16 (hrs, 2Η), 3.28 (m, 1H), 3.05 (br d, 2H), 2.37 (s5 3H), 2.20 (m, 2H), 1.93 (m, 4H). 78 Ν-2 «(4 · Nitrobenzyl &gt; 〇-trifluoroethenylamine) Trifluoroacetic acid needle (10.6 ml) dissolved in digas methane (J00 ml) was added dropwise &lt; rc especially Stir in a solution of 2,6 · dimethylpyridine (II4 liters) and nifediphenamine hydrochloride (15i g, 75 mmol). This mixture was stirred overnight at 25 ° 0 under argon: Then, it was washed with dilute citric acid (x2), washed with water, and dried (Na2S04). ★ The material in the organic phase gave the title compound as a pale yellow solid (09 · 04 g). Note 79 7-nitro-1,2,3,4-Tian argon_2_Sanqi Ditongji Yizhilin 55 This paper is sized for China National Standard (CNS) A4 (210X297 mm) (Please read first Note on the back, please fill in this page again) 4. "Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 509687 A7 __ ^ _ B7 V. Description of the invention (54) According to GE Stock, Westphany Express, 1996, 37, According to the method 5453, N-2 (4-nitrophenyl) ethyl-trifluoro 6-spotamine (D78, 2.26 g, 9.15 mmol) and paraformaldehyde (P in acetic acid (10 ml)) 45g, I4 · 4 mmol) and concentrated H2S04 (15ml) when stirred at 25¾ 卞 for 20 Φ. Upon completion, the title compound (2.17 g) was obtained as a white solid. ! HNMR (250MHz, Coa3) δ (ppm): 8.10 (m5 2H) »7J8 (t, 1H), 4 · 92-4 · 85 (2xs, 2H), 3.92 (m, 2H), 3.10 (m , 2H). MH + 274-Note 80 7-Acetylene-1,2,3,4-Tetraarginoisopropaneline at room temperature using a solution of potassium carbonate (46.6 g) in 10/0 aqueous methanol (660 ml) Hydrolysis of 7-nitro-1,2,3,4-tetrahydro-2-trifluoro-i-isopropylquinoline (79,! 7.2 g, 63 mmol) with "digas methane" (the title compound ( 11 g). Description 81 2-methyl-7-reading 1,2,3,4-tetraargon is notorious according to GM * Carrera and DS Gavi, Journal of Heterocyclic Chemistry, 1992, 29, 847 In this method, 7-nitro 4,2,3,4 · tetraargon isoquinoline (D80, 2.08 g, 11.7 mmol) was mixed with 88% formic acid (345 ml) and 37 % Aqueous formaldehyde (5.88 ml) was treated for 2 hours. It was basified with 10% potassium hydroxide and then extracted with ethyl acetate to obtain a coloring solution (<2.3 g). The title compound (1.7 g) of orange solid vessel was obtained with 0_3% methanol / ethyl acetate. Mffi93. Note 82 56 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) '(Please read first (Notes on the back then fill out this page)

經濟部中央標準局員工消費合作社印製 509687 A7 __ B7 五、發明説明（55 ) 7-胺基-2-甲基-1，2,3,4-四氬美夺考 於大氣壓下，將溶於甲酵(40毫升)之2_甲基-7-硝基-i，2,3,4-四氫異竣琳（D&amp;l，〇·25克丨1.3毫莫耳），以10%複（ip〇 毫克）上鈀進行氬化過夜。藉由通過珍藻土整線遍濾移除 該摧化#h並於真空中蒸發，獲得白色固邋標題化合物（213 毫克）6ΜϊΤ163。 說明83 8·溴峻考_2,4·二羧醃 將7-溴彀紅（10克，0.044莫耳，皇家學會會報，1958，148， 481)加至溶於Η20 (64毫升）之經攪拌ΚΟΗ (213克， 0.38莫耳）溶液超過1分鐘，隨後加入丙酮酸（5.35毫升， 0.077莫耳)超過i分鐘，結果溶液於室溫下'攪拌1小時， 然後於回流下加熱1·5 φ時，然後冷卻至室溫，以H20( 1〇〇 毫升）稀釋並過濾。將濾液以濃HC1酸化至pH 1，遍濾， 並將固體以H20洗滌，且於真空中乾燥。標題化合物為棕 色固髏（10.1克，77%) · lH NMR (250MHz, c^DI^SO) δ (ppm) ： 8.92 (dd, 1H) ^ 8.64 (s，1H)，8·44 (dd，iH)，7·86 (UH) » 未觀察到酸性質子。 說明84 &amp;識喹琳冰羧釀 將溶於硝基苯（40毫升）之8·溴喹琳·2,4·二羧酸（DS3， 克’ 34毫莫本）於回流下加熱2小時，然後使其冷卻至 室溫，以已烷（60毫升）稀釋，並濾出棕色固醴標題化合 物（8.5 克，1〇〇%)。 57 本紙張尺度適用中國國家標準（(：1^)八4規格（210父297公釐） (請先閲讀背面之注意事項再填寫本頁) 、?τ 509687 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（56 ) ^NMR (250MHz, d6DMS〇)§ (ppm) ： 8.95 (d, 1H) ^ 8.50 1H)，8.04 (ddJH)，7,82 (d，1H)，7.44(t，lk)。未觀察到酸 性質子。 , 緣明85 心笨基巉考羧饞 使用類似於說明2之方法，自S·溴喹淋《4-羧酸（D84)和 苯基硼酸製備檁題化合物，獲得棕色固體（63%) β lHNm (250MHz, CDC13) δ (ppm) ： 9.12(4 1H) ^ 8.89 (dd, 1H)，8.05 (d，1H)，7·84_7·73 (m，2H)，7·68-7·64 (ιΰ，2H)， 7.54-7.40 (哗，3H) '酸性質子未可識別， 說明86 8*苯基峻考-4-基異氰貌繼 使用類似於說明1之方法，自8-苯基喹淋-4-羧酸（D85) 製備標題化合物。使用異氱酸酯甲笨液，無需濃縮成淨 化合物。 說明87 基-2-甲基笨基碾酸 在氬氣下於Ot：時，將經攪# ‘溴-3-甲基苯胺（20克，〇· 1〇7 莫耳）和溶於二氣甲烷（250牽升）之三乙胺（33毫升，0.237 莫耳）溶液以溶於二氣甲烷（100毫升）之雙(氣二甲基甲 矽懷基)6燒（25.3克，0·12莫耳）溶液逐滴寒理超過15分 鐘。將此混合物溫至室溫，嚴攪拌20小時，然後遇濾並於 真空中濃縮。以60-80汽油（400毫升）萃取謅殘餘物，並 於真空中濃縮該濾液，剩下橙色油（35克，100%)安定鹼。 58 本紙張尺度適用中國國家標準（ CNS &gt; Α4規格（210X297公釐） (諸先聞讀背面之注意事項再填寫本頁) -^ 經濟部中央標準局員工消費合作社印製 509687 A7 __B7 五、發明説明（57 ) 將此溶解於乾THF(400毫升）中，於氬氣卞-65°C時冷凍， 並以溶於己烷（52毫升，0.13莫耳）之2.5 Μ正-丁基鋰逐 滴處理超過1分鐘。將此混舍物於-651C下揉拌1小時，然 後以三異丙基獨酸毚（30毫#，0.13莫耳）逐滴處琛超過 10分鐘，於-65°C下攪拌另1·5小時，然後以玲和水性gCl 溶液（100毫升）處理，並使其溫至室溫《以水（200毫升） 稀释此混合物，以濃HC1酸(50毫升）酸化，攪拌加分鐘， 然後於真空中濃縮至大約400毫升體積。將此水性殘餘物 以6酸乙籲洗滌，然後並藉由添加_艟K2C03鹼化。將此 驗性混合物以乙酸6酯萃取，並將萃取物乾燥（Na2S〇4) JL當固艘開始沈澱出時，於真空中濃縮至大約150毫升髏 積。將此混合物冷卻至S1G，並將國雒濾出i乾燥，獲得白 色固艘本標題化合物（9·2克，51%)。 !H NMR (250 MHz, d6DMSO) δ (ppm) ： 7.69 (d, 1H) &gt; 6.40-6.32 (m，2H)，5·34 (br s，2H)，2J2 (s，3H)。未觀察到 酸性質子。 說明鉍 冬(2,6_二甲基被·‘基&gt;_3·甲基笨联 使南類似於說明2之方法，自4_氣-二甲基赴咬（化學 摘要’ I952 ’ 46 ’ 454!)和4·-胺基-2τ甲泰苯基蝴酸（j)§7) 製備檁題化合物，獲得米黃色固體（4%) · ^NMR (250MHz, CDC13) δ (ppm) ： 7.01 (4 Itt) ^ fe.9〇 (s? 2H)，6.62-6.54 (m，2H)，3.70 (br s，2H)，2.55 (s5 6¾) , 2.22 (MH)。 59 本紙張尺度適用中國國家標準（CNS ) A4規格(210X297公釐） ~ ' ~ (請先閲讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 509687 A7 __ B7 V. Description of the invention (55) 7-Amino-2-methyl-1,2,3,4-Tetragonal is tested at atmospheric pressure and will be dissolved 2-methyl-7-nitro-i, 2,3,4-tetrahydroisojunlin (D &amp; l, 0.25 g, 1.3 mmol) in formazan (40 ml), at 10% Compound (ip0 mg) was argonized overnight on palladium. This mash #h was removed by filtering through the entire line of celite and evaporated in vacuo to obtain the title compound (213 mg) 6ΜϊΤ163 as a white solid. Note 83 8 · Bromo test _2,4 · Dicarboxylic acid salt 7-bromopyrene (10 g, 0.044 mol, Proceedings of the Royal Society, 1958, 148, 481) was added to the dissolution in Η20 (64 ml) The solution was stirred for more than 1 minute, followed by the addition of pyruvate (5.35 ml, 0.077 mole) for more than 1 minute. As a result, the solution was' stirred at room temperature for 1 hour, and then heated under reflux for 1.5 minutes. At φ, it was then cooled to room temperature, diluted with H20 (100 ml) and filtered. The filtrate was acidified to pH 1 with concentrated HC1, filtered through, and the solid was washed with H20 and dried in vacuo. The title compound is a brown solid skull (10.1 g, 77%) · lH NMR (250MHz, c ^ DI ^ SO) δ (ppm): 8.92 (dd, 1H) ^ 8.64 (s, 1H), 8.44 (dd, iH), 7.86 (UH) »No acid proton was observed. Description 84 &amp; quinine ice carboxyl brewed will be 8 · bromoquinine · 2,4 · dicarboxylic acid (DS3, g'34 mmol) dissolved in nitrobenzene (40 ml) under reflux for 2 hours Then, it was allowed to cool to room temperature, diluted with hexane (60 ml), and the title compound (8.5 g, 100%) was filtered off as a brown solid. 57 This paper size applies to Chinese national standards ((: 1 ^) 8 4 specifications (210 father 297 mm) (please read the precautions on the back before filling out this page),? Τ 509687 A7 B7 employee consumption of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the cooperative V. Explanation of the invention (56) ^ NMR (250MHz, d6DMS〇) § (ppm): 8.95 (d, 1H) ^ 8.50 1H), 8.04 (ddJH), 7,82 (d, 1H), 7.44 ( t, lk). No acid proton was observed. , Yuanming 85 Cardiobenzyl Cocoazone. Using a method similar to Note 2, the title compound was prepared from S. bromoquine 4-carboxylic acid (D84) and phenylboronic acid, and a brown solid (63%) β was obtained. lHNm (250MHz, CDC13) δ (ppm): 9.12 (4 1H) ^ 8.89 (dd, 1H), 8.05 (d, 1H), 7.84_7 · 73 (m, 2H), 7.68-7 · 64 ( ιΰ, 2H), 7.54-7.40 (Wa, 3H) 'The acidic proton is unrecognizable, indicating 86 8 * phenyl Junka-4-yl isocyanate. Using a method similar to that in Note 1, since 8-phenyl Quinine-4-carboxylic acid (D85) The title compound was prepared. Isoformate is not required to be concentrated to neat compounds. Description 87-yl-2-methylbenzyl glutamic acid under argon at Ot: will be stirred with 'bromo-3-methylaniline (20 g, 0.17 mol) and dissolved in two gases A solution of triethylamine (33 ml, 0.237 moles) in methane (250 liters) was burned in bis (aerodimethylsilyl) wax (25.3 g, 0.12 Mol) solution dropwise for more than 15 minutes. The mixture was warmed to room temperature, stirred vigorously for 20 hours, then filtered and concentrated in vacuo. The radon residue was extracted with 60-80 gasoline (400 ml), and the filtrate was concentrated in vacuo to leave an orange oil (35 g, 100%) diazepam. 58 This paper size applies to Chinese national standards (CNS &gt; Α4 size (210X297 mm) (please read the notes on the back before filling out this page)-^ Printed by the Central Consumers Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 509687 A7 __B7 Description of the invention (57) This was dissolved in dry THF (400 ml), frozen at -65 ° C in argon, and 2.5 M n-butyllithium dissolved in hexane (52 ml, 0.13 mol). Dropwise treatment for more than 1 minute. Knead the mixture at -651C for 1 hour, and then use triisopropylisocyanate (30 mmol #, 0.13 mole) dropwise for more than 10 minutes, at -65 Stir for another 1.5 hours at ° C, then treat with Linghe aqueous gCl solution (100 ml) and allow it to reach room temperature. Dilute the mixture with water (200 ml) and acidify with concentrated HC1 acid (50 ml). , Stirred for minutes, and then concentrated in vacuo to a volume of about 400 ml. This aqueous residue was washed with ethyl acetate, and then basified by the addition of 艟 K2C03. This test mixture was extracted with 6 acetate And the extract was dried (Na2S〇4) JL when the fixed vessel began to precipitate out, concentrated in vacuo to Approximately 150 ml of skeletal product. This mixture was cooled to S1G, and the hydrazone was filtered off and dried to obtain the title compound (9.2 g, 51%) as a white solid.! H NMR (250 MHz, d6DMSO) δ ( ppm): 7.69 (d, 1H) &gt; 6.40-6.32 (m, 2H), 5.34 (br s, 2H), 2J2 (s, 3H). No acidic protons were observed. Bismuth winter (2, 6_Dimethyl group · 'group> _3 · Methylbenzyl group is similar to the method described in Example 2, from 4_Ga-dimethyl to bite (Chemical Abstract' I952 '46' 454!) And 4 · -Amino-2τ-methaphenylphenyl acid (j) §7) Preparation of the title compound to obtain a beige solid (4%) · NMR (250MHz, CDC13) δ (ppm): 7.01 (4 Itt) ^ fe .90 (s? 2H), 6.62-6.54 (m, 2H), 3.70 (br s, 2H), 2.55 (s5 6¾), 2.22 (MH). 59 This paper size applies to China National Standard (CNS) A4 specifications (210X297mm) ~ '~ (Please read the notes on the back before filling this page)

509687 A7 B7 五、發明説明（58 ) 經濟部中央標準局員工消費合作社印製 說_893_甲基甲基-此啶-2_基&gt; 笨麋 使用類似於說明2之方法，自2-溴-6·甲基此啶和4-胺棊-2-甲基苯基硼酸&lt;D37)製備標題化合物，獲得米黃色爾體 (100%) 〇 ^NMR(250MHz,CDC13)5(ppm) ： 7.65^7.55(m, 1H) ^ 7.2^2 (d，1H)，7·15(4ίΗ)，7,05(41H)，6.62*6j5(m，2H)，3.6S (br s，2H)，2.59 (s，3H)，2·31 (s，3H)。 說明905_羧基-萘-1_基硼酸 在氬氣下於_6(TC時，將經攪拌溶於乾THF (1000毫升）之 5-溴-1-萘甲酸（法國化學學會通報，1968，ί , 2957，22.3 克，0·089莫耳）溶液，以溶於己烷（125毫升，0.20莫耳） 之1·6Μ正-丁基鋰逐滴處理超過15分鐘。常加入第一當量 時，自最初棕色溶液獲得米黃色沈澂，两再將第二當量加 入時，其可再度溶解。將此結果溶液於_60°C下攪拌40分 鐘，然後將三異丙基硼酸鹽（51毫升，0.22莫耳）加入， 並在逐漸溫至-lOt前，將此混合物於-60°C下攪拌另1小 1 i 1 1 時。將鉋和水性NH4CI溶叙（100毫升）加入，随後以水(400 毫升），然後以5MHC1酸（200毫升）。料此結果混合物 於真空中濃縮至大约1000毫井癥積，然後藉由添加40% NaOH溶液鹼化，並以乙酸乙德洗務將過量HC1酸加至水 相，並將沈澱出之固體濾出，以水洗滌並乾燁，獲轉白色 固髏（9.67克），其包含大約50%本標題化合物和1-萘酸令 60 (請先閲讀背面之注意事項再填寫本頁) 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（59 ) 說明91 心(6-甲基-λ矣-2-基萘甲酸 使用類似於說明2 &lt;方法，自2-溴-6_甲基此咬和5_叛基_ 萘-1-基删酸（D90)製備標題化合物，獲得米黃色固艎 (46%) 〇 lHNMR(250MHz,d6DMSd)δ (ppm) ： 8.90(d51H) &gt; 8.13(d, 1H)，8.06((141H)，7.84(tJH) i 7M(t, lH)，K2.7.46(m， 2H)，7.41 (d，1H)，7.32 (d，lH)，2·55(s5 3H)、未觀察到酸 性質子。 說明92 f(6碲基4啶-2_基&gt;萘-1-基其氰酸壤 使用類似於說明1之方法，自5&lt;6-甲塞-吡^-2-基)小寮甲 酸（D91)製備標題化合物b不將異氰酸酯單離，使用其甲 苯溶液於後續步驟。 說明93 5_(6,甲基-此贫基)-1-蔡平酸 經濟部中央標準局員工消費合作社印製 (請先聞讀背面之注意事項再填寫本頁) 使用類似於說明31之方法，自5-氣-2,3-二氫-6_(4-甲基六氫 吡讲4-基)4H-吲哚（D13)製備標邀化合物，獲得米黃色 固饉（96%) 〇 lH NMR (250MHz9 CDCI3) δ (ppm) ： «.02 (s, &gt; 7.25 (s, lH)，4.29(t，2H)，3.19(t，2H)O.10&lt;bis,4H)，2.64(bfs，4H)， 2.39 &lt;s，3H) e 說明94 S·氣_2,3_二氫_6喊六氳病蟒+基&gt;rl-三氣己醯基-1HHI哚 61 本紙張尺度適用中國國家標準（CNS〉A4規格（210X297公釐） 509687 A7 B7 五、發明説明（60 ) 將二異丙基乙胺（3.50毫升，20毫莫耳）加至氬氣下，溶 於1，2-二氣乙烷（200毫升）之經攪拌5-氣-2,3_二氫各(‘ 甲奉六氫此讲小基)二氟乙釀，基丨蛛（Ε&gt;93，7.0克，20 毫莫卑）溶液中，隨後以氣甲酸1·氣乙_ (435毫升，40 毫莫耳）。待經1小時後，以稀NaHC03(aq)洗滌該混合物， 然後乾燥（NaJOt)並於真空中濃縮，獲得棕色固體（8 86 克，100%)。將溶於MeOH懸浮液於回流下攪拌3小時， 然後使其冷卻，並於袁空中#出MeOH。將CH2CV分離， 並將水相以CH2C!2 (2x50毫升）再萃取❶組合有機相，乾 燥（NaiSO4)，並於真空中濃縮，獲得棕色固體標題化合 物（4.79 克，72%)。509687 A7 B7 V. Description of the invention (58) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs _893_methylmethyl-this pyridin-2_yl &gt; Stupid moose uses a method similar to Note 2, since 2- Bromo-6 · methyl this pyridine and 4-aminopyrene-2-methylphenylboronic acid (D37) to prepare the title compound to obtain a beige crystalline body (100%). NMR (250 MHz, CDC13) 5 (ppm) : 7.65 ^ 7.55 (m, 1H) ^ 7.2 ^ 2 (d, 1H), 7.15 (4ίΗ), 7,05 (41H), 6.62 * 6j5 (m, 2H), 3.6S (br s, 2H) , 2.59 (s, 3H), 2.31 (s, 3H). Description 905_carboxy-naphthalene-1_ylboronic acid under argon at _6 (TC, 5-bromo-1-naphthalenecarboxylic acid dissolved in dry THF (1000 ml) with stirring (Bulletin of the French Chemical Society, 1968, ί, 2957, 22.3 grams, 0.089 moles) solution, treated with 1.6M n-butyllithium dissolved in hexane (125 ml, 0.20 moles) dropwise for more than 15 minutes. Often when the first equivalent is added A beige-colored sinker was obtained from the initial brown solution, and it was dissolved again when the second equivalent was added twice. The resulting solution was stirred at _60 ° C for 40 minutes, and then triisopropylborate (51 ml , 0.22 moles), and before gradually warming to -lOt, stir this mixture at -60 ° C for another 1 hour 1 i 1 1. Add planer and water-based NH4CI (100 ml) and then add Water (400 ml), then 5 MHC1 acid (200 ml). The result was that the mixture was concentrated in vacuo to approximately 1000 milliwells, then basified by adding 40% NaOH solution, and washed with ethyl acetate. An excess of HC1 acid was added to the aqueous phase, and the precipitated solid was filtered off, washed with water and dried to obtain a white solid skull (9.67 g). Contains about 50% of the title compound and 1-naphthoic acid order 60 (please read the precautions on the back before filling this page) The size of the paper is applicable to China National Standard (CNS) A4 (210X297 mm) 509687 A7 B7 V. Description of the invention (59) Description of 91 (6-methyl-λ--2-ylnaphthoic acid) is similar to that of the description 2 &lt; method, from 2-bromo-6_methyl this bite and 5_tyl_naphthalene- 1-yl deleted acid (D90) to prepare the title compound to obtain a beige solid (46%). 0HNMR (250MHz, d6DMSd) δ (ppm): 8.90 (d51H) &gt; 8.13 (d, 1H), 8.06 ((141H ), 7.84 (tJH) i 7M (t, lH), K2.7.46 (m, 2H), 7.41 (d, 1H), 7.32 (d, 1H), 2.55 (s5 3H), no acid properties were observed Note 92 f (6 telluryl 4-pyridin-2-yl) naphthalen-1-yl and its cyanate are similar to those in Note 1, since 5 &lt; 6-methan-pyridin-2-yl) is small The formic acid (D91) was used to prepare the title compound b without isolating the isocyanate, and its toluene solution was used in the subsequent steps. Note 93 5_ (6, methyl-this-poor group) -1-Caiping acid Employees' Cooperative of the Central Standards Bureau Printed (please read the notes on the back before filling out this page) Method 31, the title compound was prepared from 5-gas-2,3-dihydro-6_ (4-methylhexahydropyridine 4-yl) 4H-indole (D13), and a beige solid tincture (96%) was obtained. ) 0H NMR (250MHz9 CDCI3) δ (ppm): «.02 (s, &gt; 7.25 (s, lH), 4.29 (t, 2H), 3.19 (t, 2H) O.10 &lt; bis, 4H), 2.64 (bfs, 4H), 2.39 &lt; s, 3H) e Explanation 94 S · qi_2,3_dihydro_6 hexapodase python + group &gt; rl-trifluorohexanyl-1HHI indole 61 Paper size applies Chinese national standard (CNS> A4 specification (210X297 mm) 509687 A7 B7 V. Description of the invention (60) Diisopropylethylamine (3.50 ml, 20 mmol) is added under argon and dissolved 1,2-Digas ethane (200 ml) after stirring 5-Gas-2,3_dihydro each ('methyl Feng hexahydro small base) difluoroethyl brewing, radical 丨 spider (E &gt; 93, 7.0 g, 20 mmol), followed by acetic acid 1 · gas B (435 mL, 40 mmol). After 1 hour, the mixture was washed with dilute NaHC03 (aq), then dried (NaJOt) and concentrated in vacuo to obtain a brown solid (8 86 g, 100%). The suspension in MeOH was stirred at reflux for 3 hours, then allowed to cool and #MeOH was removed in Yuan Kongkong. The CH2CV was separated and the aqueous phase was re-extracted with CH2C! 2 (2x50 ml). The combined organic phase was dried (NaiSO4) and concentrated in vacuo to obtain the title compound (4.79 g, 72%) as a brown solid.

!H NMR (250 MHz? €DC13) δ (ppm) ： 8.00 (s?# 1H) ^ 7.25 (s? 1H)，4·30 (t，2印，3·20 (t5 2H)，3.10-3.08 (br m，8H)。NH 不可識別。 說明95 6學基六氫4b #小基氬-2,3-二氳小三氟乙醮基. ΙΗ^Ι^ 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 將於冰中冷卻，溶於CH2C12 (50毫升）之經攪拌5-氣-2,3-二氫-6-(六氫此讲-ϊ·基)-1-三氟乙醢基-1Η·吲#溶液，以醋 酸辭（〇·34克，3.3毫莫卑）處理，然後使其溫至室溫。待 經6小時後，以稀NaHC03(aq)洗滌該混合物，乾燥 (Na2S04),並於真空中濃縮，獲得棕色函體標題化合物 (110 克，97%)。 'Η NMR (250 MHz, GDC13) δ &lt;ppm) ： 7.98 (s51H) &gt; 7.26 (s5 62 本紙張尺度適用中國國家標準（CNS ) A4規格（2l〇X297公釐) 經濟部中央標準局員工消費合作社印製 509687 A7 ___B7 五、發明説明（61 ) 1Η)，4·31 (t，2H)，3.79(brs，2Η)，3·64 (brs，2Η&gt;，3·21 (t，2H)， 3·05-3·00 (m5 4Η)，2·15 (s，3Η)。 說明96 甲基-碟啶·2-基&gt;4-萘甲酸 使用類似於說明33之方法’自6·(4·匕聽基六氫此_小 基)-5-氣_2,3-二氫-1-三氟〇醮基‘1Η_吲哚（j)95)製備標題 化合物，獲得棕色泡沫（81%)。 i NMR (250MHz，CDC13) δ (ppm) : 7·〇9 (s，1Η)，6·33 (s， 1Η)，3·79-3·75 (m，2Η)，3·63-3·54 (m5 4Η)，3.01-2.91 (m， 6Η)，2·13 (s，3Η)。ΝΗ 不可識別。 說明97 5-氣-2,3_二氳《6_(4_乙基六氬此蟒哚 在氬氣下室溫時，將溶於THF (30毫升）之經攪拌6-(4_乙 醯基六氫吡4-1-基)-5·氣-2,3-二氫_1_三氟乙醯基-1H-吲哚 (D95，0·65克，2·3毫莫耳）溶液，以溶於THF(9.3毫升， 9.3毫莫耳）1M硼烧_THF錯合物處理，然後於回流下加熱 5小碑。將此混合物冷卻至〇乞，然後以溶於申酵（25毫升） 之濃HC1 (6毫升）遂滴處理。待經30分鐘後，將此溶液 加熱回流2小時，然後於真空中濃縮。將殘餘物以乙酸乙 酯（50毫升）和2MHC1酸（40毫升）處理，搖晃完全並 分雔水層，议K2C03檢化，且以二氣甲就萃取。將萃取物 乾燥（NaA〇4)，於真空中濃縮，並藉由層析術將殘餘物 於矽石凝膠上以2_10%甲醇/二氣甲烷溶析而純化，獲得米 黃色固體標題化合物（0·31克，50%)。 63 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 考· 509687 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（62 ) iHNMR(250MHz,d6DMSO)5(ppm) ： 7.07 (s, 1H) » 6.41 (Sa 1H)，3.73 (brs51H)，3·56 (t，2H)，3 03 (brΜΗ)，2.97 (t，2H), 2·63 (br s，4H)，2.49 (q5 2H)? U3 (ζ 3H)。 說明98 6_【4-(第工-T4氧基嫌&gt;基)六氮说讲-1-基氣氣‘1_立 氟乙龜基-m_喵嗛 — 使用類似於説明95之方法，自5-氣·2,3-二氫_6·(六氟吨讲· 1-基)4-三氟乙醯基_1Η-,ι^ (D94)和二碳酸二-第三.丁_ 製備標題化合物，獲得棕色泡沫（100%)。 H NMR (250MHz，CDCI3) δ (ppm) : 7·99 (s，1Η)，7k26 (s 1Η)，4·30 (t，2Η)，3·60 (t，4Η)，3·20 (t，2Η)，2.98 仏 4Η), I.49(s，9H)〇 , 竦明99 6-【4_{第三-丁氧基叛基)六氳4脅·ι·基丨各氣_2,3-二氬 使用類似於說明33 &lt;方法，自6_[4-(第三-丁氧基幾基)六氫 此讲-1-基]_5-氣-2,3-二氫_1-三氟乙醯基-1H·,嘴（d98)製 備標題化合物，獲得棕色固體（84%)。 H NMR (25DMHz, CDCI3) δ (ppm) ： 7.08 (s, 1H) ^ 6.35 (s, 1H)，3.60-3.53 (tn，紐），3,10-2.89 (m，6H)，i.4g (s，9H), NH不可識別。 親明U)0 (第三-丁象基羰基)六氬成务1-基】各氣·2,3^二氬 («Λ咬-4·基)萘-丨“基胺基羰基丨-1Η-冷蜂 64 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） &quot;- (請先閲讀背面之注意事項再填寫本頁} 訂 509687 A7 _______B7 五、發明説明（63 ) 使用類似於實施例4之方法，自4-(4b啶-4-基)萘·1·基胺 (D2)和6_[4_(第三-丁氧基羰基)六氫4嵴-1-基】·5-氣-2&gt; 二氫，1Η·吲哚（D99)製備梯題化合物，獲得黃色/棕色固 體（67%)。 lH NMR (250MHz5 CDG13) δ (pjim) ： 8.74 (d9 2H) » 7.99 (d, 1H)，7.9U7.86 ㈣ 3H)，7·67·7·41 (ιη，5H)，7·21 (s，1H)， 6.81 (s51H)，4.31 (t，2H)，3.56 (t，4H)，3.30&lt;t，2H) · 2·96 (t， 4H)，1.46&lt;s，9H)。 說明101 6-丨4-(第三-丁氣基槊基)六氬赴蟒·!-基I各氣-2,3-二氣 (成咬·4-基 &gt;萘_1 ‘基磨基羧基】 使用類似於實施例4之方法’自5-(4t咬*4·基)祭-1-基胺 (D74 )和(第三-丁氧基羰基)六氫此讲小基】各氣-2&gt; 二氫-1Η·吲哚〇&gt;99)製備標題化合物，獲得黃色/棕色固 體（74%) 〇 經濟部中央標準局員工消費合作社印製 ^ NMR (250MHz, CDC13) δ (ppm) ： 8,75 (d, 2H) » 7.85 (s5 1H)，7·78-7·42 ㈣，7H)，7.21 (s，1H)，6·74 (s，1H)，4·30 (t， 2H)，3.56 (t5 4H)，3.30 (t，2H)，2.95 (t，4H)，1·45 (s，9H)。 說明102 4·(畚嵴4基体甲蝮 使用類似於說明24之方法，自3-氣嗒讲及4-羧基苯基硼酸 製備檁題化合物，獲得棕色固髏（《7%)。MS ·’ m/z-199 (M-H) 〇 說明103 65 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 經濟部中央標準局員工消費合作社印製 509687 A7 ______B7 五、發明説明（64 ) (略讲-2_基}笨甲酸· 使用類似於說明24之方法，自2-氣嗒讲及4-羧基苯基硼酸 t備標題化合物，獲得白色揮邋（88%)。MS ; m/z=l56 (MtC02)-説明104 6-笨基叙酸 使用類似於說明24之方涞，自6_氣煙蘇及苯基珊觫製備標 題化合物，獲得純白色固體（54%)。MS: m/z=20G (MIT)。 規明105 4_(6_甲基-嗒4_3，基&gt;笨甲酸 使用類似於說明24之方法，自3-氣甲基嗒讲及‘羧基苯 基硼酸製備標題化合物，獲得黃色固髏（52%)❶Ms : m/z=213 (M-H) 〇 說明106 4-(‘氟基-3_甲基苯基&gt;笨甲酸 使用類似於說明24之方法，自4-溴-2-甲基苯基氰及4-叛基 苯基硼酸製備檁題化合物，獲得白色固體（75%)。MS : m/z=236 (M-H) 〇 說明107 ‘(心甲基·噚巉，2-基}笨麽 將5_甲基-2&lt;4-瑞基苯基)嘮峰(化學治療1973，8(4&gt;，437) (3·0克，15毫莫耳)和溶於THF (75毫升）混合物1〇〇/β 碳（0.25克）上把，於氫氣麼下搜拌24小時。將此混合物 濾移，並於真空中濃縮至乾，獲得淺米色粉末標題化物 66 ( CNS ) )&quot; (請先閲讀背面之注意事項再填寫本頁) 訂 509687 A7 B7 五、發明説明（¢5 ) 經濟部中央標準局員工消費合作社印製 (2.29 克，89°/〇&gt;。 1H)，6·73 饨 2H)，5 74 (s，讲），2.42 (s，3H) 〇 說明108 5«硝基基羧醮联 將溶於αί2〇2( 200毫升）之經攪拌5-硝基_萘小基羧酸（化 學物理通報1将4，32(1〇&gt;，3%8) (3.5〇克，I6奄蓽卑） 懸浮液，以乙二醯氣（2.1毫升，24毫莫耳）和DMF (2 滴）處理。於室溫下攪拌此混合物5小時❶將此溶液於真 空中濃縮至乾，並將殘餘物溶解於乾THF (200奪升）。緩 慢將氨鼓泡通入該溶液中0·5小時*將此混合物於真空中濃 縮至乾並將殘餘物與水研磨，且將固谶濾出並於真空中乾 燥，獲得淺棕色#末標題化合物（3·34克，95%)。 4 NMR (250 MHz，d6DMSO) δ (ppm) ·· 8.47 (d，1Η)， 8·23-8·13 (m，2H)，8·05 (s，1H)，7·71·7·59 (m，4H)。 讓明109 Ν·【Η二甲基赡基}亞6基】-Ml基萘基羧鏟雎 將經攪拌5·硝基-萘^基羧ϋ胺（D108，1.50克，7毫莫耳） 和Ν，Ν-二甲基己醢胺混合物加熱至ll〇°C2小時。將經冷卻 之混合物α水（20毫升）稀釋，並將沈澱p體濾出，以水 洗滌，並於真空中乾燥，獲得淺棕色粉末標题化合物（L60 束，80〇/〇) · lU NMR 050 MHz, CDC13) δ (ppm) ： 9.31 (d, 1H) - 8.53 (d, 1H)^ 8.22 (dd, 1H) ^ 8.15 (dd, 1H) ^ 7.72-7.56 (m?2H) ^ 3.19 67 (請先聞讀背面之注意事項再填寫本頁) -訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 ___________B7 五、發明説明（66 ) (4, 6H)，2·45 (s，3H)。 說明110 3-甲基基“萘·1·基)^i，2,4««f 二連 將Κ·Ϊ1，(二甲基胺基)亞乙基]4硝基萘小基羧鏟胺 (m〇9，1·55克，5·4毫莫耳）加至羥胺鹽酸鹽（0·47克， 6·75毫莫耳）和溶於70%水性醋酸〇〇毫并）之5MNa〇ti 溶液（1·35毫升，6J75毫莫耳）之經攪拌溶液t。將此混 合物溫至8〇t：4小時，然後冷卻，敢以水（50毫升）稀釋。 將沈澱固體濾出，以水洗滌，並於真空中乾燥，剩下淺米 色粉末標題化合物（1·ίΐ克，80%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 9.52 (4 1Η) ^ 8.71 (d5 1H)，8.44 (dcUH)，8.25 (dd，1H)，7.87-7.73 , 2,59 (s? 3H) 〇 說明111 5_(3·甲基_1，2,‘噚二崚_七基)萘4-基胺 使_類似於說明71之方法★自3-甲基-5-(5-硝基萘-1·基 U，4-f二唑（D110)製備標題化合物，獲得淺黃色粉末 (54%)- 經濟部中央標準局員工消費合作社印製 -----------—-- (請先閱讀背面之注意事項再填寫本頁) ^1. ^NMR (250MHz，CDC13) δ (ppm) : 8.52 (d，1H)，8.30 (dd， 1H)，8·09 (d，1H)，7·58-7·44 (p5 2H)，6.S8 (dd，1H)，4.23 (s， 2H)，2·56 (s，3H)。 說_ 112 S·硝基•化炔丙基萘4_基羧錳胺 將溶於CH2C12 (50毫升）之經挽拌5-硝基萘4-基羧酸（化 68 石氏張尺度適用中國國家標準（CNS ) A4規格（210X297公瘦1 ~ 經濟部中央標準局員工消費合作社印製 509687 A7 ______B7 五、發明説明（67 ) 學物理通報J984，32(1〇&gt;，3%8) (1.10克，5毫莫耳）懸 浮液，以乙二醢氣（〇·5毫升，6毫莫耳&gt;和〇娜（1滴） 處理β待於室溫下3小時後，將此混合物於真空中濃縮堇 乾。將殘餘物溶解於CH2G32 (30毫升），以三乙胺（Ϊ.4 毫微升，10毫莫耳）處理，隨後將溶於CH2CI2 U(H|升） 之炔丙胺（0·28克，5牽莫耳）溶液逐满加入❶待於室溫下 攪拌18小時後，將此混合物以水洗滌，乾燥（Na2S〇4), 並於真空中濃縮至乾。將殘餘物與二已醚研磨，獲得淺黃 色粉末標題化合物（〇·79束，61%)。 ^NMR (250 MHz, CDC13) δ (ppm) ： 8.62 (t, 2Η) » 8.24 (d, 1H)，7/73,7·知(m，3H)，6·30 (s，1H)，4.34 (&lt;M，2H)，2·33 (t， 1H)。 · 說明113 5-甲基冬(s-硝基萘小基 &gt;嘩嶙 將經攪拌5-硝基缺丙基萘小基羧醢胺（m 12，0.75克， 3毫莫耳）和溶於冰醋酸（毫升）之醋醆汞（〇.Q4克，〇·ι2 毫莫耳）混合物加無至©流4小時。將經冷卻混合物於真 空中乾燥至乾，並將殘餘物溶解於CH2〇2，以水性K2C03 溶液洗滌，乾燥（Na2S04)並於真空中濃縮至乾。藉由急 騍層析術將殘餘物於矽名凝繆上，以CH2fl2溶析，獲得黃 色粉末標題化合物（0·50克，66%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 9.75 (d, 1H&gt; * 8.54 (4 1H)，8·19(41Η)，7.79-7名4(m，2H)，7·〇1 (s，1H)，2.47(s， 3H)〇 69 本紙張尺度適用中國國家標準（CNS ) A4規格( 210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁)! H NMR (250 MHz? € DC13) δ (ppm): 8.00 (s? # 1H) ^ 7.25 (s? 1H), 4 · 30 (t, 2 imprints, 3.20 (t5 2H), 3.10-3.08 (br m, 8H). NH is not identifiable. Description 95 6 学 基 hexahydro 4b # 小 基 Argon-2,3-difluorene small trifluoroethylfluorenyl. ΙΗ ^ Ι ^ Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling in this page) It will be cooled in ice and dissolved in CH2C12 (50 ml). Stirred 5-gas-2,3-dihydro-6- (This talk about hexahydro-ϊ · Group) -1-trifluoroacetamido-1Η · ind # solution, treated with acetic acid (0.34 g, 3.3 mmol), and then allowed to warm to room temperature. After 6 hours, dilute NaHC03 (aq) The mixture was washed, dried (Na2S04), and concentrated in vacuo to obtain the title compound of brown funnel (110 g, 97%). 'Η NMR (250 MHz, GDC13) δ &lt; ppm): 7.98 (s51H ) &gt; 7.26 (s5 62 This paper size is in accordance with Chinese National Standard (CNS) A4 specifications (210 × 297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 ___B7 V. Description of the invention (61) 1Η), 4 · 31 (t, 2H), 3.79 (brs, 2Η), 3.64 (brs, 2Η &gt;, 3.2 1 (t, 2H), 3.05-3.00 (m5 4Η), 2 · 15 (s, 3Η). Explanation 96 Methyl-dipridine 2-yl> 4-naphthoic acid is used similarly to explanation 33 Method 'from the title "6. (4. Benzyl hexahydro this _ small group) -5-gas _2,3-dihydro-1-trifluorooxoyl' 1 _ indole (j) 95) Compound to obtain a brown foam (81%). i NMR (250MHz, CDC13) δ (ppm): 7.09 (s, 1Η), 6.33 (s, 1Η), 3.79-3 · 75 (m, 2Η), 3.63-3 · 54 (m5 4Η), 3.01-2.91 (m, 6Η), 2.13 (s, 3Η). ΝΗ is not identifiable. Note 97 5-Gas-2,3_dihydrazone <6_ (4_ethylhexagon. This python is dissolved in THF (30 ml) with stirring at room temperature under argon. Hexahydropyridine 4--1-yl) -5 · Ga-2,3-dihydro_1-trifluoroethylfluorenyl-1H-indole (D95, 0.65 g, 2.3 mmol) solution , Treated with 1M boron-THF complex dissolved in THF (9.3 ml, 9.3 mmol) and heated under reflux for 5 millimeters. The mixture was cooled to 0, and then dissolved in Shen Ye (25 ml ) Concentrated HC1 (6 ml) was then treated dropwise. After 30 minutes, the solution was heated at reflux for 2 hours, then concentrated in vacuo. The residue was taken up in ethyl acetate (50 ml) and 2MHC1 acid (40 ml). Treat, shake completely and separate the aqueous layer, analyze K2C03 and extract with dichloromethane. Dry the extract (NaA04), concentrate in vacuo, and chromatograph the residue on silica. The gel was purified by elution with 2-10% methanol / digas methane to obtain the title compound (0.31 g, 50%) as a beige solid. 63 This paper is sized to the Chinese National Standard (CNS) A4 (210X297 mm) (Please read the notes on the back first Please fill in this page again) Booking · 509687 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (62) iHNMR (250MHz, d6DMSO) 5 (ppm): 7.07 (s, 1H) »6.41 (Sa 1H), 3.73 (brs51H), 3.56 (t, 2H), 3 03 (brMΗ), 2.97 (t, 2H), 2.63 (br s, 4H), 2.49 (q5 2H)? U3 (ζ 3H ). Explanation 98 6_ [4- (Ci-T4 oxyacyl> group) hexazine talk about -1- radical gas' 1_Lifluoroethenyl-m_Meow 嗛 — use similar to Note 95 Methods from 5-Gas · 2,3-Dihydro-6 · (Hexafluoroton ·· 1-yl) 4-trifluoroethylfluorenyl-1Η-, ι ^ (D94) and di-carbonate di-third. D_ The title compound was prepared to obtain a brown foam (100%). H NMR (250MHz, CDCI3) δ (ppm): 7.99 (s, 1Η), 7k26 (s 1Η), 4.30 (t, 2Η), 3 · 60 (t, 4Η), 3.20 (t, 2Η), 2.98 仏 4Η), I.49 (s, 9H) 〇, 竦 明 99 6- [4_ {Third-butoxyalkyl group) Hexa 氲 4 氲 · ι · 基 丨 Each gas _2,3-diargon is used in a similar manner to that described in 33 &lt; from 6_ [4- (Third-butoxyquinyl) hexahydro-1-yl ] _5-Gas-2,3-dihydro_1-trifluoroacetamido-1H ·, mouth (d98) to prepare the title compound to obtain brown Colored solid (84%). H NMR (25DMHz, CDCI3) δ (ppm): 7.08 (s, 1H) ^ 6.35 (s, 1H), 3.60-3.53 (tn, New Zealand), 3,10-2.89 (m, 6H), i.4g ( s, 9H), NH is not recognized. Affinity U) 0 (Third-Butylcarbonyl) Hexaargon 1-yl] Each gas · 2,3 ^ Diargon («ΛΛ-4 · yl) naphthalene- 丨" Aminoaminocarbonyl 丨 -1Η- Cold bee 64 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) &quot;-(Please read the precautions on the back before filling this page} Order 509687 A7 _______B7 V. Description of the invention (63) Use similar to The method of Example 4 was performed from 4- (4bpyridin-4-yl) naphthalene · 1 · ylamine (D2) and 6_ [4_ (third-butoxycarbonyl) hexahydro4 嵴 -1-yl] · 5 -Ga-2 &gt; Dihydro, 1Η · indole (D99) to prepare the title compound to obtain a yellow / brown solid (67%). LH NMR (250MHz5 CDG13) δ (pjim): 8.74 (d9 2H) »7.99 (d , 1H), 7.9U7.86 ㈣ 3H), 7.67 · 7 · 41 (ιη, 5H), 7.21 (s, 1H), 6.81 (s51H), 4.31 (t, 2H), 3.56 (t, 4H), 3.30 &lt; t, 2H) · 2.96 (t, 4H), 1.46 &lt; s, 9H). Description 101 6- 丨 4- (third-butanylfluorenyl) six argon goes to python · ! -Base I each gas -2,3-digas (bite-forming 4-group> naphthalene_1 'radical group carboxyl group] Using a method similar to Example 4' from 5- (4t bite * 4 group ) -1--1-amine (D74) and (third-butoxy Carbonyl) hexahydro small group] each gas-2 &gt; dihydro-1Η · indole 〇 &gt; 99) Preparation of the title compound to obtain a yellow / brown solid (74%) 〇 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ^ NMR (250MHz, CDC13) δ (ppm): 8,75 (d, 2H) »7.85 (s5 1H), 7.78-7 · 42 ㈣, 7H), 7.21 (s, 1H), 6.74 ( s, 1H), 4.30 (t, 2H), 3.56 (t5 4H), 3.30 (t, 2H), 2.95 (t, 4H), 1.45 (s, 9H). Explanation 102 4 · (畚 嵴The 4-form formazan was prepared by a method similar to that in Note 24, and the title compound was prepared from 3-aerobic acid and 4-carboxyphenylboronic acid to obtain a brown solid skull (<7%). MS · 'm / z-199 (MH ) 〇Note 103 65 This paper size is applicable to Chinese National Standard (CNS) Α4 size (210 × 297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 ______B7 V. Description of the invention (64) (slightly -2_base) Benzoic acid. Using a method similar to Note 24, the title compound was prepared from 2-airlazone and 4-carboxyphenylboronic acid to obtain a white hydrazone (88%). MS; m / z = l56 (MtC02) -instruction 104 6-benzylidene The title compound was prepared from 6-gassin and phenylsulfonate using a square pyrene similar to that in instruction 24 to obtain a pure white solid (54% ). MS: m / z = 20G (MIT). Regulation 105 4_ (6_methyl-da-4_3, yl) is used in a similar manner to Note 24 to prepare the title compound from 3-aminomethylda and 'carboxyphenylboronic acid' to obtain a yellow solid cross (52 %) ❶Ms: m / z = 213 (MH) 〇 Description 106 4-('Fluoro-3_methylphenyl &gt; stearic acid Use a method similar to that of Note 24, starting from 4-bromo-2-methylbenzene The title compound was prepared from cyanocyanine and 4-benzylphenylboronic acid to obtain a white solid (75%). MS: m / z = 236 (MH) 〇 Explanation 107 '(cardiomethyl · fluorene, 2-yl) Mix the 5-methyl-2 &lt; 4-renephenyl) pyrene peak (chemotherapy 1973, 8 (4 &gt;, 437) (3.0 g, 15 mmol) and dissolve in a mixture of THF (75 ml) 〇〇 / β carbon (0.25 g) handle, search and stir under hydrogen for 24 hours. This mixture was filtered and concentrated to dryness in vacuo to obtain the title compound 66 (CNS) as a light beige powder &quot; ( Please read the notes on the back before filling this page) Order 509687 A7 B7 V. Description of invention (¢ 5) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (2.29 g, 89 ° / 〇 &gt;. 1H), 6 · 73 饨 2H), 5 74 (s, speaking), 2.42 (s, 3H). Description 108 5 «Nitro-carboxyl coupling will be dissolved in αί2 02 (200 ml) with stirred 5-nitro-naphthalene small carboxylic acid (Chemical Physics Bulletin 1, 4, 32 (1〇 &gt;, 3% 8) (3.50 g, I6 奄 荜) Suspension, treated with ethylene difluoride (2.1 ml, 24 mmol) and DMF (2 drops). The mixture was stirred at room temperature for 5 hours and the solution was stirred. Concentrate to dryness in vacuo and dissolve the residue in dry THF (200 liters). Ammonia is slowly bubbled through the solution for 0.5 hours * The mixture is concentrated to dryness in vacuo and the residue is contacted with It was triturated with water, and the solids were filtered off and dried in vacuo to obtain the light brown ## title compound (3.34 g, 95%). 4 NMR (250 MHz, d6DMSO) δ (ppm) 8.47 (d, 1Η), 8.23-8 · 13 (m, 2H), 8.05 (s, 1H), 7.71 · 7 · 59 (m, 4H). Let Ming 109 Ν · [Ηdimethyldimethylfluorenyl } Sulylene group] -Ml-naphthylcarboxamidine will be stirred with a mixture of 5 · nitro-naphthylcarboxamide (D108, 1.50 g, 7 mmol) and N, N-dimethylhexamidine Heat to 110 ° C for 2 hours. Dilute the cooled mixture with alpha water (20 ml) and filter the precipitate. Out, washed with water and dried in vacuo to obtain the title compound as a light brown powder (L60 beam, 80/0) · 1U NMR 050 MHz, CDC13) δ (ppm): 9.31 (d, 1H)-8.53 (d , 1H) ^ 8.22 (dd, 1H) ^ 8.15 (dd, 1H) ^ 7.72-7.56 (m? 2H) ^ 3.19 67 (Please read the notes on the back before filling out this page) National Standard (CNS) A4 specification (210X297 mm) 509687 A7 ___________B7 V. Description of the invention (66) (4, 6H), 2.45 (s, 3H). Description 110 3-Methyl "naphthalene · 1 · yl) ^ i, 2,4« «f Diphenylene K · Ϊ1, (dimethylamino) ethylidene] 4nitronaphthalene (m09, 1.55 g, 5.4 mmol) added to 5MNa of hydroxylamine hydrochloride (0.47 g, 6.75 mmol) and 70% aqueous acetic acid 0.00 mmol) 〇ti solution (1.35 ml, 6J75 millimoles) was stirred solution t. This mixture was warmed to 80t: 4 hours, then cooled, and dared to be diluted with water (50 ml). The precipitated solid was filtered off, It was washed with water and dried in vacuo to leave the title compound (1.lΐg, 80%) as a light beige powder. LH NMR (250 MHz, CDC13) δ (ppm): 9.52 (4 1Η) ^ 8.71 (d5 1H ), 8.44 (dcUH), 8.25 (dd, 1H), 7.87-7.73, 2,59 (s? 3H) 〇 Explanation 111 5_ (3 · methyl_1,2, 'hydrazine_heptyl) naphthalene 4 -Amine-like method similar to Method 71. ★ The title compound was prepared from 3-methyl-5- (5-nitronaphthalene-1.ylU, 4-fdiazole (D110) to obtain a pale yellow powder (54 %)-Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -------------- (Please read the precautions on the back before filling out this page) ^ 1. ^ NMR (250M Hz, CDC13) δ (ppm): 8.52 (d, 1H), 8.30 (dd, 1H), 8.09 (d, 1H), 7.58-7 · 44 (p5 2H), 6.S8 (dd, 1H), 4.23 (s, 2H), 2.56 (s, 3H). It is said that 112 S · nitro • propargylnaphthalene 4-ylcarboxymanganese amine will be dissolved in CH2C12 (50 ml). 5-Nitronaphthalene 4-based carboxylic acid (Chemical 68 Shih's Zhang scale applicable to Chinese National Standard (CNS) A4 specifications (210X297 male thin 1 ~ printed by Employee Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 509687 A7 ______B7 V. Description of the invention ( 67) Bulletin of Physical Physics J984, 32 (1O &gt;, 3% 8) (1.10 g, 5 mmol) suspension with ethylene difluoride (0.5 mL, 6 mmol) and O Na (1 drop) After treating β for 3 hours at room temperature, the mixture was concentrated to dryness in vacuo. The residue was dissolved in CH2G32 (30 ml), and triethylamine (Ϊ. 4 升, 10 毫(Mol)), and then a solution of propargylamine (0.28 g, 5 mol) in CH2CI2 U (H | L) was added to the solution. After stirring at room temperature for 18 hours, the mixture was mixed with water. Washed, dried (Na2SO4), and concentrated to dryness in vacuo. The residue was triturated with dihexyl ether to obtain the title compound as a pale yellow powder (0.079 bundle, 61%). ^ NMR (250 MHz, CDC13) δ (ppm): 8.62 (t, 2Η) »8.24 (d, 1H), 7/73, 7 · K (m, 3H), 6.30 (s, 1H), 4.34 (&lt; M, 2H), 2.33 (t, 1H). · Description 113 5-methyl winter (s-nitronaphthalene small group &gt; 嶙 will stir the 5-nitropropyl deficient naphthalene small group carboxamide (m 12, 0.75 g, 3 mmol) and dissolve A mixture of acetic acid and mercury (0.04 g, 0.2 mmol) in glacial acetic acid (ml) was added to the flow for 4 hours. The cooled mixture was dried to dryness in vacuo, and the residue was dissolved in CH2 〇2, washed with aqueous K2C03 solution, dried (Na2S04) and concentrated to dryness in vacuo. The residue was chromatographed on silica gel by flash chromatography and lysed with CH2fl2 to obtain the title compound as a yellow powder (0 · 50 g, 66%) lH NMR (250 MHz, CDC13) δ (ppm): 9.75 (d, 1H &gt; * 8.54 (4 1H), 8.19 (41Η), 7.79-7 persons 4 (m, 2H ), 7.0 · 1 (s, 1H), 2.47 (s, 3H) 〇69 This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling in this page)

、1T 畸· 509687 A7 ______B7五、發明説明（68 ) 經濟部中央標準局員工消費合作社印製 說明114 S-(S，甲基私_2_基 &gt;萘_1麵基赡 使用類似於說明28之方法，自5-甲基_2气5_硝基萘“1-基)嘮 唑（Dll3)製備標越化合物，獲得黃每/綠色膠（95%)。 4 NMR (250MHz，d6DMSO) δ (ppm): 8 64 (41H)，8· 11 (賊 1Η)，7·94(4, Itt) * 7.53-7.39(m，2H)，6·97(4 1H)，6·48(4 1H)，418(S，2H)，2.45(S，3H)。 說明115 3_甲基_4·(嘯矣-2-基&gt;联 使用類似於說明2之方法’自2_演，咬和4-胺基，2·甲基苯 1 基硼酸（D87)製備標題化合物，獲得黃色固邋（的％)。 H NMR (250MHz, CDC^) δ (ppm) ： 8.76 (d/2H) » 7.75 (d, 1H) ’ 7·11 (t，1H) ’ 6·62(&lt;1，1H) ’ 6.59(s，1H)，3.78(br，2H), 2.55 (s3 3H) 〇 說明116 3-甲基·4·(_咬冬基}联 使用類似於說明2之方法，自5-溴嘧啶和基2甲基苯 ^竣Φ87)製備標題化合物，獲得稻草色微艘（91%)。 H NMR (250Kfflzy CDC13) δ (ppm) ： 9.14 (s&gt; 1H) , g 7〇 (s2H) ’ 7.67 (m，1H)，7.01 (41H)，6.65 (s，1H), 6 62 (d ’ 3.60 (br, 2H) » 2.23 (s, 3H)-說明117 2,6_二甲基典赴交 將溶於2-丁醇⑽毫升)之_拌4_氣办二甲基辦(化 70 本紙張尺度適用中國國家標準（CNS ) A4· ( 21Gx297公菱-^--------- (請先聞讀背面之注意事項再填. -裝· 11 絲 經濟部中央標準局員工消費合作社印製 509687 A7 B7 五、發明説明（69 ) 學摘要1952，46，4541) (2·6克，18毫莫耳）溶液，以 碘化鈉（174克，120毫莫耳）和4-甲苯續酸（3.4克，18 毫莫耳）處理，於氬氣下，將此混合物於回流下加熱72小 時。冷卻此反廨混合物，然後於真空中濃縮，並將殘餘物 以水（200毫升）處理，且以乙酸&amp;醸萃取。將萃取物以水 性硫代硫酸鈉溶液洗滌，然後乾燥（Na2S04)，並於處空 中濃縮，獲得白色國艎標題化合物，其可自丙酮中轉換成 其白色固饈琿酸鹽（3·44克，69%)。 iNMlU 自由鹼）(250MHz，CDCl3)8(ppm):7.37(s，2H)， 2·46 (s，6H)。MH^234 〇 說明118 5-(2,6·二甲基Wfc啶-4_基&gt;_1·萘甲皺 使用類似於說明2之方法，自2,6-二甲基4-块毗啶&lt;D117) 和5-羧基萘-1-基硼酸（D90)製備標題化合物，獲得白色 固體（70%)。 ^NMR (250MHz, d6DMSO) δ (ppm) ： 8.75 (d91H) ^ 7.99 (dd, 1H)，7.80 (d，1H)，7·60,7·52 (m，1H)，7·50-7.32 2H)， 7·00 (s，2H)，2.36 (s，6H)。未觀察到酸性質子f 說明119 5气2,心二甲暴-Λ啶_4_基&gt; 萘·1_基異氟酸繼 使用類似於說明1之方法，自Μ2,6·二甲基-此啶基&gt;1-萘甲酸（mis)製#標題化合物。不將異氟酸酯單離，使 用其甲苯溶液於後績步驟。 說明〇〇 71 本紙張尺度適用中國國家標準（CNS) A4規格（210 X297公釐） ----------#------#------費 (請先閲讀背面之注意事項再填寫本頁) 509687 Α7 Β7 五、發明説明（7〇 ) 經濟部中央標準局員工消費合作社印製 4- (2,6-二甲基-硃交_3-基)-1甲基笨赅 使用類似於說明2之方法，自3-溴-2,6-;甲基毗啶〇&gt;59a) 和4-胺基·2·甲基苯基爛酸（D87)製備標題化合物，獲得 淺黃色油（6.5%) « ^NMR (250MHz, CDC13) δ (ppm) ： 7.32-7.25 (m51H) » 7.00 (d，1H)，反87 (d，1¾，6·654·52 (m，2H)，3·67 (br s，2H)， 2·56 (s，3H)，2 2S (s，3H)，1·98 (s，3H)。 說明121 3-_基-4-(雀峻各基&gt;笨翁 使用類似於說明2之方法，自2-溴嚓唑和4-胺基-2_甲基苯 基硼酸（D87)製備標題化合物，獲得黃色/棕色油（6 5%)。 lH NMR (250MHz5 CDC13) δ (ppm) ： 7.83 (d； 1H) ^ 7.57 (d? 1H)，7.28 (mJH)，6·57 (m5 2H)，3.80(br，2H)，2.53 (s5 3H)。 說明122 SK嘧咳各基萘甲酸 使釋類似於說明2之方法，自5_溴嘧啶和孓羧基萘基硼 酸（D90)製備標題化合物，獲得米黃色囪髏（78%)。 !HlSiv!R(250MHz, d6DMSO) δ (ppm) ： 13.30 (bf91H) » 9.35 (s，1H)，9·00 (s，2H)，8·% ，&amp;19(d，丨Η) * 7·93 , 7.78 (m，1H)，7.65 (叫 2H)。說明123 5- (嫌咬-S·基)萘·1-基異氰酸葡 使用類似於說明1之方法，自5-(喊咬-5·基)-1_寮甲酸 (D122)製備標題化合物。不將異氰酸醋單離，但使用其 72 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 線#· 509687 A7 B7 五、發明説明（Ή ) 甲苯溶液於後續步驟。 說明124 5·乙醮基IM-籌麼 將經攙掸1-6龕基-5-福基萘（澳洲化學期刊1995，48(12&gt; v 1969) (0·75 克，3.5 毫莫耳）、1〇〇/Opd«c(0.20 克）和溶 甲酵（75毫升）之環已烷（10毫升）溶液，於回流下加熬 6小時。過濾經冷卻之混合物，並於真空申濃縮。將殘舞物 溶解於CHaCl2 (50毫升），以水洗滌，乾燥（Na2S04)並 濃縮至乾。將該殘餘物與醚/己烷研磨，獲得黃色/棕色粉末 標題化合物（0.52克，80%)。 XH NMR (250 MHz, CDC13) δ (ppm) ： 8.03 (t5 2H) ^ 7.83 (dd, 1H)，7.49-7.36 (m，2H)，6·«3(&lt;ί，1H)，4·17«2Η)，2 73(1 3H)〇 說明125 5_(嘧咬·2-基氧基)萘-1-基胺 使用類似於說明70之方法，自5_輕基萘4-基胺和2-溪鳴咬 製備標題化合物，獲得淺米色粉末（58%)。 H NMR (250MHz,, CDCI3) δ (ppm) ： 8.52 (d, 2H) » 7.73 ^ 經濟部中央標準局員工消費合作社印製 1H)，7·48 (t，1H)，7.40-7.21 (m，拍），7.01 (t, 1H)，6·78 (4 1H)，4·13 (s，2H)。 說明126 5-lt基萘_1_基璇 將鐵粉（θ·21克，3·7毫莫耳）和氣化銨（0於克，04毫莫 耳）加至經攪拌溶於〇醇（10毫升）和水（5毫升）之5_ 73 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨〇'〆297公釐） 509687 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（72 ) 硝基萘-1-基腈（D128，0.15克，0·76毫莫耳）懸浮液中， 然後將此混合物於回流下加熱0:5小時。稍檄將此混合物冷 卻，過濾，並於真空中濃縮❶將此殘餘物於6酸乙酯（25 產升）和水（10毫升）間進行分配β分参有機層，乾燥 (Na2S04)並濃縮至乾，獲得黃色/綠色粉末標題化合物 (011 克，80/〇)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 8.06 (d, 1H) » 7.88 (dd5 1H)，7.68 (d，1H)，7.49 (叫 2H)，6.88 (41H)，4.27 (s5 2H)-說明127 5-硝基萘-1·基腈 將溶於CH2C12 (5毫升）之2·5Μ三申基甲矽烷基填酸酯溶 液加至經攪拌溶於αΐ2α2 (10毫升）之5-硝基萘-1-基羧醯 胺（D108，0.20克，0·93毫莫耳）溶液中，並將此混合物 於回流下加熱2小時。將經冷卻混合物以水（10毫升）處 理，並待經攪拌10分鐘後，分離有機相，以聲水洗滌，乾 燥（Na2S04)並於真空中濃縮皇乾β藉由急驟層析術將殘 餘物於發石凝膠上以CH2C12溶析而純化，獲得無色粉末標 題化合物（0.12克，66%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 8.82 &lt;d? 1H) ^ 8.57 (d? 1H)，8.06(d，1¾，7,83 (m，2H)。 說明 5*·硝基_萘-1。基醮胺游 將羥胺翬酸鹽（1.23克，1/78毫莫耳）加至溶於甲醇（10 毫升）之氩氧化鈉（0.71克，1·78亳莫耳）溶液中。將此 74 本紙張又度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 A7 -*——---—~— _ B7 五、發明説明（73 ) 混合物以5-硝基萘-μ基腈（D127 ,1 6〇克，8j毫莫耳） 處理，並於回流下加熱48小時α將經冷卻混合物藉由蒸發 濃縮至10毫升，然後並以水(50毫升）處理。收集沈澱物， 以水洗滌並於真家中乾燥，淺黃色粉末裱題化合物（165 克，88%) * HNMR (250 MHz, d6DMS〇) δ (ppm) ： 9.74 (s? 1H) ^ 8.66 (4 1H) ’ 8.30 (m，2H)，7抓7·72 (m5 3H)，6·14 (s，2H)。 說明129 甲基各(5·读基蔡-1_基)_1，2,4-考二冷 將乙醯氣（0.78毫升，11毫莫耳）逐滴加至溶於此啶（1〇 亳升）之綠攪拌5_硝基i萘-μ基醯胺肟⑺⑶，1.28克，5.5 毫莫耳）溶液中。將此混合物於室溫卞攪拌〇Γ5小時，然後 加熱至回流24小時。將經冷卻混合物以水（1〇0毫升）處 理，並以乙酸乙酯（3x25毫升）萃取。以稀HC1、水洗滌 經組合有機相萃取物，乾燥（Na2S04)並濃縮至乾❶藉由 急驟層析術將殘餘物於矽石凝膠上以CHiCl2溶析，獲得淺 黃色粉末標題化合物（0.86克，61%)。 經濟部中央標準局員工消費合作社印製 'Η NMR (250 MHz, C〇a3) δ (ppm) ： 9.27 (d91H) &gt; 8.63 (d, IH)，8·36 (紙 1H)，8.24 (tid，iH}，7.81 (q，1H)，7·69 (q，1H), 2 J7 (s，3H) 0 說明130 5-(5-甲基-1，2,4*今二凌各基)萘小基胺 根據說明126所略述方法製備標題化合物，獲得棕色膠。 將此轉換成其鹽酸鹽，獲得灰色粉末。 75 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 五、發明説明（74 ) i7 Γ88Γ871Τ :專利申請案第871058G號 ^jpCPatent Appln, No,-8? 1·0?84ΐ~^ 修 中文說明書第76至13S( 1 -附体二 Ά509687 A7 ______B7 V. Description of the invention (68) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 114 S- (S, methyl private _2_yl &gt; naphthalene_1 facet 赡 Use similar to the instructions Method 28, the preparation of the standard compound from 5-methyl-2-nitronaphthalene "1-yl) oxazole (Dll3), to obtain yellow per green glue (95%). 4 NMR (250MHz, d6DMSO) δ (ppm): 8 64 (41H), 8.11 (Thief 1Η), 7.94 (4, Itt) * 7.53-7.39 (m, 2H), 6.97 (4 1H), 6.48 (4 1H), 418 (S, 2H), 2.45 (S, 3H). Explanation 115 3_methyl_4 · (xiao 矣 -2-yl) combined with a method similar to description 2 'Since 2_play, bite The title compound was prepared with 4-amino, 2-methylbenzene 1-boronic acid (D87) to obtain a yellow solid (%). H NMR (250MHz, CDC ^) δ (ppm): 8.76 (d / 2H) » 7.75 (d, 1H) '7.11 (t, 1H)' 6.62 (&lt; 1, 1H) '6.59 (s, 1H), 3.78 (br, 2H), 2.55 (s3 3H) 〇 Explanation 116 3 -Methyl · 4 · (_Bentyl) was used in a similar manner to Explanation 2 to prepare the title compound from 5-bromopyrimidinyl and 2-methylbenzene ^ 竣 Φ87) to obtain a straw-colored microvessel (91%). H NMR (250Kfflzy CDC13 ) δ (ppm): 9.14 (s &gt; 1H), g 7〇 (s2H) '7.67 (m, 1H), 7.01 (41H), 6.65 (s, 1H), 6 62 (d' 3.60 (br, 2H) »2.23 (s, 3H) -Instruction 117 2,6_Dimethyl code will be delivered to be dissolved in 2-butanol ⑽ml) _mixed 4_Gas office dimethyl office Standard (CNS) A4 · (21Gx297 male diamond-^ --------- (Please read and read the precautions on the back before filling in. -Packing · 11 Silkworm Ministry of Economic Affairs, Central Standards Bureau, staff consumer cooperative print 509687 A7 B7 V. Description of Invention (69) Scientific Abstracts 1952, 46, 4541) (2.6 g, 18 mmol) solution with sodium iodide (174 g, 120 mmol) and 4-toluene acid (3.4 G, 18 mmol), the mixture was heated under reflux for 72 hours under argon. The reaction mixture was cooled, then concentrated in vacuo, and the residue was treated with water (200 mL) and treated with Acetic acid &amp; hydrazone extraction. The extract was washed with an aqueous sodium thiosulfate solution, then dried (Na2S04), and concentrated in the air to obtain the title compound of white national salamander, which can be converted from acetone to its white solid salt (3.44 g) , 69%). iNM1U free base) (250 MHz, CDCl3) 8 (ppm): 7.37 (s, 2H), 2.46 (s, 6H). MH ^ 234 〇 Description 118 5- (2,6 · Dimethyl Wfcpyridin-4_yl group> _1-naphthylmethyl wrinkle Use a method similar to Note 2 from 2,6-dimethyl 4-block pyridine &lt; D117) and 5-carboxynaphthalene-1-ylboronic acid (D90) to prepare the title compound to obtain a white solid (70%). ^ NMR (250MHz, d6DMSO) δ (ppm): 8.75 (d91H) ^ 7.99 (dd, 1H), 7.80 (d, 1H), 7.60, 7.52 (m, 1H), 7.50-7.32 2H ), 7.0 (s, 2H), 2.36 (s, 6H). No acidic proton f was observed 119 5 gas 2, cardiomethyl-Amidin_4_yl &gt; naphthalene · 1-yl isofluoric acid. Using a method similar to that of Note 1, from M2,6 · dimethyl -This pyridyl group> 1-naphthoic acid (mis) #Title compound. Instead of isolating the isofluoroester, the toluene solution was used in the subsequent step. Note 〇71 This paper size applies to Chinese National Standard (CNS) A4 (210 X297 mm) ---------- # ------ # ------ Fee (please first Read the notes on the back and fill in this page) 509687 Α7 Β7 V. Description of the invention (70) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 4- (2,6-dimethyl-Zhujiao_3-based)- 1Methylbenzidine is prepared from 3-bromo-2,6-; methylpyridine 0> 59a) and 4-amino · 2 · methylphenyl rotten acid (D87) using a method similar to that described in Note 2. Title compound to give a pale yellow oil (6.5%) «NMR (250MHz, CDC13) δ (ppm): 7.32-7.25 (m51H)» 7.00 (d, 1H), trans 87 (d, 1¾, 6.654 · 52 (m, 2H), 3.67 (br s, 2H), 2.56 (s, 3H), 2 2S (s, 3H), 1.98 (s, 3H). Explanation 121 3-_Base-4 -(Jin Junjiji) &gt; Beng uses a method similar to that in Preparation 2 to prepare the title compound from 2-bromoxazole and 4-amino-2-methylphenylboronic acid (D87) to obtain a yellow / brown oil ( 6 5%). LH NMR (250MHz5 CDC13) δ (ppm): 7.83 (d; 1H) ^ 7.57 (d? 1H), 7.28 (mJH), 6.57 (m5 2H), 3.80 (br, 2H), 2.53 (s5 3H). Description 122 SK The naphthoic acid was similar to the method described in explanation 2. The title compound was prepared from 5-bromopyrimidine and fluorenylcarboxynaphthylboronic acid (D90) to obtain a beige chimney (78%).! HlSiv! R (250MHz, d6DMSO) δ (ppm): 13.30 (bf91H) »9.35 (s, 1H), 9.00 (s, 2H), 8.%, &amp; 19 (d, 丨 Η) * 7.93, 7.78 (m, 1H), 7.65 (called 2H). Note 123 5- (Like bite-S · yl) naphthalene · 1-yl isocyanate. Using a method similar to Note 1, since 5- (call bite-5 · yl) -1_ 寮Formic acid (D122) is used to prepare the title compound. Isocyanate is not isolated, but its 72 paper size is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) (Please read the precautions on the back before filling this page ) Order line # · 509687 A7 B7 V. Description of the invention (Ή) The toluene solution will be used in the subsequent steps. Note 124 5. · Ethyl fluorenyl IM-chip will pass through 搀 掸 1-6 fluorenyl-5-furyl naphthalene (Australian chemistry Journal 1995, 48 (12 &gt; v 1969) (0. 75 g, 3.5 mmol), 100 / Opd «c (0.20 g) and cyclohexane (10 ml) solution of formazan (75 ml) , Boil for 6 hours under reflux. The cooled mixture was filtered and concentrated in vacuo. The residue was dissolved in CHaCl2 (50 ml), washed with water, dried (Na2S04) and concentrated to dryness. The residue was triturated with ether / hexane to give the title compound (0.52 g, 80%) as a yellow / brown powder. XH NMR (250 MHz, CDC13) δ (ppm): 8.03 (t5 2H) ^ 7.83 (dd, 1H), 7.49-7.36 (m, 2H), 6. «3 (&lt; ί, 1H), 4.17 «2Η), 2 73 (1 3H). Note 125 5_ (pyrimidine · 2-yloxy) naphthalen-1-ylamine. Using a method similar to Note 70, from 5-light naphthalene 4-ylamine and 2 -Ximing bite to prepare the title compound to obtain a light beige powder (58%). H NMR (250MHz ,, CDCI3) δ (ppm): 8.52 (d, 2H) »7.73 ^ Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, printed at 1H), 7.48 (t, 1H), 7.40-7.21 (m, Shot), 7.01 (t, 1H), 6.78 (4 1H), 4.13 (s, 2H). Note 126 5-ltylnaphthalene_1_jixuan adds iron powder (θ · 21 g, 3.7 mmol) and ammonium vaporized (0 g, 04 mmol) to a solution of 0 alcohol with stirring ( 10ml) and water (5ml) of 5_ 73 This paper size applies to Chinese National Standard (CNS) A4 specification (2 丨 〇297mm) 509687 Printed by A7 B7, Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Explanation (72) Nitronaphthalene-1-ylnitrile (D128, 0.15 g, 0.76 mmol) was suspended in this suspension, and then the mixture was heated under reflux for 0: 5 hours. The mixture was cooled, filtered, and concentrated in vacuo. The residue was partitioned between ethyl 6 acid (25 liters) and water (10 mL). The β-separated organic layer was dried (Na2S04) and concentrated. To dryness, the title compound was obtained as a yellow / green powder (011 g, 80/0). lH NMR (250 MHz, CDC13) δ (ppm): 8.06 (d, 1H) »7.88 (dd5 1H), 7.68 (d, 1H), 7.49 (called 2H), 6.88 (41H), 4.27 (s5 2H)- Note 127 5-nitronaphthalene-1 · nitrile. Add 2.5M trishenylsilyl succinate solution in CH2C12 (5 ml) to 5-nitro, which is dissolved in αΐ2α2 (10 ml). In a solution of naphthalene-1-ylcarboxamide (D108, 0.20 g, 0.93 mmol), the mixture was heated under reflux for 2 hours. The cooled mixture was treated with water (10 ml), and after stirring for 10 minutes, the organic phase was separated, washed with sonic water, dried (Na2S04) and concentrated in vacuo. The dried β was removed by flash chromatography. It was purified by lysing with CH2C12 on a hair stone gel to obtain the title compound (0.12 g, 66%) as a colorless powder. lH NMR (250 MHz, CDC13) δ (ppm): 8.82 &lt; d? 1H) ^ 8.57 (d? 1H), 8.06 (d, 1¾, 7,83 (m, 2H). Explanation 5 * · nitro_ Naphthalene-1. Sulfonamide. Hydroxylamine sulfonate (1.23 g, 1/78 mmol) was added to a solution of sodium argon oxide (0.71 g, 1.78 mmol) in methanol (10 ml). .This 74 paper is again applicable to the Chinese National Standard (CNS) Α4 specification (210X297 mm) (Please read the precautions on the back before filling this page) Order A7-* ——---- ~~ _ B7 5 Description of the invention (73) The mixture was treated with 5-nitronaphthalene-μnitrile (D127, 160 g, 8j millimoles), and heated under reflux for 48 hours. The cooled mixture was concentrated to 10 by evaporation. Ml, then treated with water (50 ml). The precipitate was collected, washed with water and dried in a real home, light yellow powder mounting compound (165 g, 88%) * HNMR (250 MHz, d6DMS〇) δ (ppm ): 9.74 (s? 1H) ^ 8.66 (4 1H) '8.30 (m, 2H), 7 grab 7.72 (m5 3H), 6.14 (s, 2H). Explanation 129 methyl groups (5 · read Ji Cai-1_ Ji) 1,2,4- Kao Erliang will be Ethane gas (0.78 ml, 11 mmol) This piperidine was added dropwise to a solution (1〇 milliliters) stirring the green 5_ nitro i -μ naphthyl group amidoxime ⑺⑶, 1.28 g, 5.5 mmol) was added. The mixture was stirred at room temperature for 5 hours and then heated to reflux for 24 hours. The cooled mixture was treated with water (100 mL) and extracted with ethyl acetate (3 x 25 mL). The combined organic phase extract was washed with dilute HC1, water, dried (Na2S04) and concentrated to dryness. The residue was lysed on a silica gel with CHiCl2 by flash chromatography to obtain the title compound as a pale yellow powder (0.86 G, 61%). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Η NMR (250 MHz, C〇a3) δ (ppm): 9.27 (d91H) &gt; 8.63 (d, IH), 8.36 (paper 1H), 8.24 (tid , IH}, 7.81 (q, 1H), 7.69 (q, 1H), 2 J7 (s, 3H) 0 Description 130 5- (5-methyl-1, 2, 4 * this two eryl) Naphthylamine was prepared according to the method outlined in Note 126 to obtain a brown gum. This was converted to its hydrochloride salt to obtain a gray powder. 75 This paper is sized to the Chinese National Standard (CNS) A4 (210X297 mm) V. Description of the invention (74) i7 Γ88Γ871T: Patent Application No. 871058G ^ jpCPatent Appln, No, -8? 1.00? 84ΐ ~ ^ Revised Chinese Specification Nos. 76 to 13S (1-附体 二 Ά)

Amended Pages 76 to 139 of the Chinese Specification- Enel. II (88年8月C日送呈） (Submitted on August 17，1999 ) 經濟部智慧財產局員工消費合作社印製 4 NMR( HC1 鹽）(250MHz，CD3OD) δ (ppm): 8·72 (t，1H)， 8·08 (dd，1H)，7·91 (d5 1H)，7.60 (dd，1H)，7.44 (d，2H)， 4.63 (s，2H)，2.46 (s，3H)。 實施例1 1-【(4_澳-3-甲基苯基)胺基叛基】-5-甲氧基-6-(4-甲基六氮 吡呼_1_基)巧丨哚 於氬氣下，將第三-丁氧化鉀（59毫克，0.50毫莫耳）加 至溶於無水THF (10毫升）之5-甲氧基-6-(4-甲基六氫吡 &quot;井_1-基)弓卜朵（130毫克，0.50毫莫耳，WO95/06637中間 物2)溶液中，並將此混合物攪拌15分鐘。將溶於無水 THF (10毫升）之4_溴_3_甲基苯基異氰酸酯（D1，127 毫克’ 0.60毫莫耳）溶液中。於氬氣下室溫時攪拌結果混 合物16時，然後真空中濃縮。藉由管柱層析術將殘餘物 於矽石凝膠上以〇_6%MeOH/CH2Cl2溶析，獲得淺黃色固 體標題化合物（108毫克，45%)。 4 NMR (250 MHz，CDC13) δ (ppm) : 7.67 (d，1H)，7·34 (d， 1H)，7·30 (d，1H)，7·21 (d，1H)，7·05 (d(UH)，6.86 (s，1H)， 3·76 (s，3H)，3.03 (br s5 4H)，2.59 (br s，4H)，2.25 (s, 6H)。 實施例2 H(4-溴士甲基苯基)胺基羰基】-2,3_二氩：甲氡基_6-(φβ 甲基六氩吡畊-1_基丨哚 將溶於二氯曱烷（10毫升）之2,3-二氫-5-甲氣基_6_(4_甲 基六氫吡畊_1_基)-1Η-吲哚（0.10克，0.40亳莫耳，w〇 76 本紙張又度適用中國國家榡準（CNS ) A4規格（210X297公釐） 請 先 閲 讀 背 之 注 意 事 項 再Amended Pages 76 to 139 of the Chinese Specification- Enel. II (Submitted on August 17, 1999) 4 NMR (HC1 salt) printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (250MHz, CD3OD ) δ (ppm): 8.72 (t, 1H), 8.08 (dd, 1H), 7.91 (d5 1H), 7.60 (dd, 1H), 7.44 (d, 2H), 4.63 (s, 2H), 2.46 (s, 3H). Example 1 1-[(4-A-3-methylphenyl) aminomethyl] -5-methoxy-6- (4-methylhexaazapyridin_1-yl) Under argon, tertiary-butoxide (59 mg, 0.50 mmol) was added to the 5-methoxy-6- (4-methylhexahydropyridine) well in anhydrous THF (10 ml). 1-based) Gongbuduo (130 mg, 0.50 mmol, WO95 / 06637 Intermediate 2) solution, and the mixture was stirred for 15 minutes. It was dissolved in a solution of 4-bromo-3-methylphenyl isocyanate (D1, 127 mg '0.60 mmol) in anhydrous THF (10 ml). The resulting mixture was stirred at room temperature under argon for 16 hours and then concentrated in vacuo. The residue was eluted on silica gel by column chromatography with 0-6% MeOH / CH2Cl2 to obtain the title compound (108 mg, 45%) as a pale yellow solid. 4 NMR (250 MHz, CDC13) δ (ppm): 7.67 (d, 1H), 7.34 (d, 1H), 7.30 (d, 1H), 7.21 (d, 1H), 7.05 (d (UH), 6.86 (s, 1H), 3.76 (s, 3H), 3.03 (br s5 4H), 2.59 (br s, 4H), 2.25 (s, 6H). Example 2 H (4 -Bromomethylmethylphenyl) aminocarbonyl] -2,3-diargon: methylamidino-6- (φβ methylhexanidine-1_yl) indole will be dissolved in dichloromethane (10 ml ) Of 2,3-dihydro-5-methylamino-6- (4-methylhexahydropyridine_1-yl) -1Η-indole (0.10 g, 0.40 mol, w〇76 paper Applicable to China National Standard (CNS) A4 (210X297 mm) Please read the precautions before reading

訂 線 509687 A7 B7五、發明説明（75 ) 經濟部智慧財產局員工消費合作社印製 95/06627中間物3)加至溶於二氯曱烷（10毫升）之4-溴-3-曱基苯基異氰酸酯（D1，0.11克，0.50毫莫耳）溶 液中。於室溫下攪拌此混合物17時，然後真空中濃縮， 獲得暗黃色油。以乙酸乙酯攪拌該油，產生黃色固體標題 化合物，將其濾出並乾燥（0·17克，92%)。 lH NMR (250 MHz, CDC13) δ (ppm) ： 7.59 (s5 1H) ^ 7.36 (d? 1H)，7.03 (dd，1H)，6.65 (s，1H)，6.25 (s51H)，3.98 (t5 2H)， 3.76(s，3H)，3.13(brs，4H)，2.54 (brs，4H)，2.30 (s，3H)， 2.28 (s，3H)。 實施例3 l-【(2,3-二氣苯基)胺基羰基】·2,3-二氩-5-甲氧基-6-(4-甲基 六氬吡畊·1·基)-1Ηβ丨哚 依照實施例2之類似方法，自2,3-二氯苯基異氰酸酯和 2.3- 二風-5-甲氧基-6-(4-甲基六風。比11井-1-基)-1Η- 口引σ朵 (WO95/06627中間物3)製備標題化合物。 4 NMR (250MHz，CDC13) δ (ppm) : 8.27 (dd，1Η)，7.68 (s， 1Η)，7.23-7.13 (m，2H)，7.15 (dd5 1H)，6·75 (s5 1Η)，4.15 (t，2H)，3.85(s，3H)，3.22(t，2H)，3.13 (brs，4H)，2.63 (br s，4H)，2.36 (s，3H)。 實施例4 2.3- 二氮_5-甲氣基-6_(4_甲基六氮吼喷·1_基)_1-[4-(峨咬-4_ 基)茶小基胺基数基】-弓丨嘴 將4-(吡啶-4-基)萘1-1基胺（D2，196毫克，0.89毫莫耳） 和溶於CH2C12(10毫升）之NEt3(90毫克，0.89毫莫耳） 77 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填- 丨隊-- 育Line 509687 A7 B7 V. Description of the invention (75) 95/06627 Intermediate printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 3) Added to 4-bromo-3-fluorenyl group dissolved in dichloromethane (10 ml) Phenyl isocyanate (D1, 0.11 g, 0.50 mmol) in solution. The mixture was stirred at room temperature for 17 hours and then concentrated in vacuo to obtain a dark yellow oil. The oil was stirred with ethyl acetate to give the title compound as a yellow solid, which was filtered off and dried (0.17 g, 92%). lH NMR (250 MHz, CDC13) δ (ppm): 7.59 (s5 1H) ^ 7.36 (d? 1H), 7.03 (dd, 1H), 6.65 (s, 1H), 6.25 (s51H), 3.98 (t5 2H) , 3.76 (s, 3H), 3.13 (brs, 4H), 2.54 (brs, 4H), 2.30 (s, 3H), 2.28 (s, 3H). Example 3 l-[(2,3-Difluorophenyl) aminocarbonyl] · 2,3-Diargon-5-methoxy-6- (4-methylhexahydropyridine · 1 · yl) -1Ηβ 丨 indole According to a similar method to that in Example 2, from 2,3-dichlorophenyl isocyanate and 2.3-difluoro-5-methoxy-6- (4-methylhexan. Than 11 wells -1- Base)-1Η-ortho-sigma (WO95 / 06627 Intermediate 3) to prepare the title compound. 4 NMR (250MHz, CDC13) δ (ppm): 8.27 (dd, 1Η), 7.68 (s, 1Η), 7.23-7.13 (m, 2H), 7.15 (dd5 1H), 6.75 (s5 1Η), 4.15 (t, 2H), 3.85 (s, 3H), 3.22 (t, 2H), 3.13 (brs, 4H), 2.63 (br s, 4H), 2.36 (s, 3H). Example 4 2.3- Diazol-5-methylamino-6- (4-methylhexazine-1.yl) _1- [4- (Ebino-4_yl) Tetraylamine amino group]-bow丨 Put 4- (pyridin-4-yl) naphthalene 1-1ylamine (D2, 196 mg, 0.89 mmol) and NEt3 (90 mg, 0.89 mmol) in CH2C12 (10 ml) 77 copies Paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the notes on the back before filling-丨 Team-Yu

、1T -線· 509687 A7 ___B7 五、發明説明（76 ) 經濟部智慧財產局員工消費合作社印製 溶液逐滴加至氬氣下溶於CH2C12( 1〇亳升）之三光氣（84 毫克，0.28毫莫耳）經攪拌溶液中超過3〇分鐘。待經完 成添加後，將此混合物於室溫下授拌15分鐘，然後將溶 於CH2C12 (10毫升）之2,3-二氫-5-甲氧基各(4_甲基六氯 吡畊小基)-1Η-吲哚（WO95/06627中間物3，200毫克， 0.81毫莫耳）溶液加入。待經6小時後，以1〇%Na2C〇3(aq) 洗蘇混合物’乾燦（NajO4) ’並於真空中濃縮，獲得粗 製綠色油’藉由層析術將其於石夕石凝膠上以2-5% MeOH/CHfl2溶析而純化。獲得米黃色固體標題化合物 (292 毫克，73%)。 H NMR (250MHz，CDC13) δ (ppm): 8.73 (dd，2H)，7.99 (dd， 1H)，7·91 (d，1H)，7.88 (dd，1Η)，7·75 (s，1H)，7·6(μ7·49 (m， 2H) ’ 7·46 (d，1H) ’ 7.42 (dd，1H)，6.81. (s，ih)，6.77 (s，1H)， 4.27 (t，2H)，3·85 (s，3H) ’ 3.28 (t，2H)，3 11 (br s，4H)，2.60 (br s，4H)，2.60 (br s，4H)，2.34 (s，3H)。 實施例5 2,3-二氬-5-甲氧基-6-(4-甲基六氩吼__[基)小【5_(4-峨唆 基)萘·1·基胺基羰基HH-嘈哚 使用實施例2之類似方法，自5-(吡啶-4-基)萘-1-基異氰酸 酯（D4)和2,3-二氫-5-甲氧基_6·(4-曱基六氫吡畊-1-基)-1Η-吲哚（WO95/06627中間物3)製備標題化合物。 4 NMR (250MHz，CDC13) δ (ppm) : 8.72 (d，2Η)，8.02 (d， 1Η)，7.74 (s，1H)，7.72 (d，1H)，7.66 (d，1Η)，7·55 (t，1H)， 7·41^7·46 (m，2H)，7.40 (d，2H)，6.85 (s，1H)，6·75 (s，1H)， 78 (請先閲讀背面之注意事項再填· 訂 線· 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐) 509687 A7 B7 五、發明説明（77 經濟部智慧財產局員工消費合作社印製 4.21 (t，2H)，3.84 (s, 3H)，3.24 (t，2H)，3.07 (br s，4H)，2.31 (s，3H) 〇 實施例61-[(2,3_二氯-4_(吡啶斗基)苯基胺基羰基]-2,3-二氩_5-甲氧 基-6-(4-甲基六氩吡畊小基)_1Η_ι*5ΐ哚 使用實施例4之類似方法，自2,3-二氣-4-(吡啶-4-基)苯胺 (D7 )和2,3_二氫_5_甲氧基-6-(4-甲基六氫吡讲小基HH-吲哚（WO95/06627中間物3)製備標題化合物，獲得橙 色/棕色固體（54%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.67 (d，2H)，8·41 (d， 1H)，7·70 (s，1H)，7·36 (d，2H)，7·27 (s，1H)，7·26 (d，1H)， 6.76 (s5 1H)，4.18 (t，2H)，3.85 (s，3H)，3.24 (t，2H)，2·71 (br s，4H)，2·41 (s，3H) 〇 實施例72,3_二氩各甲氧基-6-(4-甲基六氩吡畊小基)小啉_5_基 胺基羰基)-1Η_吲嗦 使用實施例4之類似方法，自5-胺基喳唯和2,3-二氫-5-甲氧基冬(4·甲基六氫吡畊小基)_1H-吲哚（WO95/06627 中間物3)製備標題化合物。 4 NMR (250MHz，CDC13) δ (ppm): 8·92 (dd，1H)，8.27 (dd， 1H)，7.99 (t，1H)，7.69-7.71 (m，3H)，7.41 (dd，1H)，6.75 (s，1H)，6.70 (s，1H)，4.20 (t，2H)，3.85 (s，3H)，3.25 (t，2H)， 3.09 (br s，4H)，2.59 (br s，4H)，2.32 (s，3H)。實施例8 79 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 請 先 閲 讀 背 之 注 意 項 再 裝、 1T-line · 509687 A7 ___B7 V. Description of the invention (76) The solution printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs was added dropwise to argon and dissolved in phosgene (84 mg, 0.28) in CH2C12 (10 liters). Millimoles) were stirred in the solution for more than 30 minutes. After the addition was completed, the mixture was stirred at room temperature for 15 minutes, and then 2,3-dihydro-5-methoxy each (4-methylhexachloropyridine) dissolved in CH2C12 (10 ml) was added. Small group) -1H-indole (WO95 / 06627 intermediate 3,200 mg, 0.81 mmol) was added. After 6 hours, wash the mixture 'Dancan (NajO4)' with 10% Na2C03 (aq) and concentrate in vacuo to obtain a crude green oil 'which was chromatographed on Shixi stone gel It was purified by eluting with 2-5% MeOH / CHfl2. The title compound was obtained as a beige solid (292 mg, 73%). H NMR (250MHz, CDC13) δ (ppm): 8.73 (dd, 2H), 7.99 (dd, 1H), 7.91 (d, 1H), 7.88 (dd, 1Η), 7.75 (s, 1H) , 7 · 6 (μ7 · 49 (m, 2H) '7.46 (d, 1H)' 7.42 (dd, 1H), 6.81. (S, ih), 6.77 (s, 1H), 4.27 (t, 2H ), 3.85 (s, 3H) '3.28 (t, 2H), 3 11 (br s, 4H), 2.60 (br s, 4H), 2.60 (br s, 4H), 2.34 (s, 3H). Example 5 2,3-Diargon-5-methoxy-6- (4-methylhexaarginyl __ [yl] small [5- (4-erimyl) naphthalene · 1 · aminoaminocarbonyl HH -Indol, using a similar method as in Example 2, from 5- (pyridin-4-yl) naphthalene-1-yl isocyanate (D4) and 2,3-dihydro-5-methoxy-6 · (4- 曱Hexahydropyridin-1-yl) -1Η-indole (WO95 / 06627 intermediate 3) to prepare the title compound. 4 NMR (250MHz, CDC13) δ (ppm): 8.72 (d, 2Η), 8.02 (d, 1Η), 7.74 (s, 1H), 7.72 (d, 1H), 7.66 (d, 1Η), 7.55 (t, 1H), 7.41 ^ 7 · 46 (m, 2H), 7.40 (d, 2H), 6.85 (s, 1H), 6.75 (s, 1H), 78 (Please read the precautions on the back before filling in. • Threading • This paper size applies to China National Standard (CNS) A4 specifications (21 OX 297 (Mm) 509 687 A7 B7 V. Description of the invention (77 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 4.21 (t, 2H), 3.84 (s, 3H), 3.24 (t, 2H), 3.07 (br s, 4H), 2.31 ( s, 3H) 〇 Example 61-[(2,3-dichloro-4_ (pyridinyl) phenylaminocarbonyl group] -2,3-diargon-5-methoxy-6- (4-methyl Hexahydropyridine) _1Η_ι * 5pyridine Using a method similar to that in Example 4, from 2,3-digas-4- (pyridin-4-yl) aniline (D7) and 2,3_dihydro_5 -Methoxy-6- (4-methylhexahydropyridyl) HH-indole (WO95 / 06627 intermediate 3) to prepare the title compound to obtain an orange / brown solid (54%). 4 NMR (250MHz, CDC13 ) δ (ppm): 8.67 (d, 2H), 8.41 (d, 1H), 7.70 (s, 1H), 7.36 (d, 2H), 7.27 (s, 1H), 7 · 26 (d, 1H), 6.76 (s5 1H), 4.18 (t, 2H), 3.85 (s, 3H), 3.24 (t, 2H), 2.71 (br s, 4H), 2.41 (s , 3H) 〇 Example 72, 3_ diargon each methoxy-6- (4-methyl hexapyridine small group) small morpholine_5_ylaminocarbonyl group) -1Η_indene use Example 4 A similar method was obtained from 5-aminopyridine and 2,3-dihydro-5-methoxydong (4 · methylhexahydropyridine) _1H-indole (WO95 / 06627 Intermediate 3) The title compound was prepared. 4 NMR (250MHz, CDC13) δ (ppm): 8.92 (dd, 1H), 8.27 (dd, 1H), 7.99 (t, 1H), 7.69-7.71 (m, 3H), 7.41 (dd, 1H) , 6.75 (s, 1H), 6.70 (s, 1H), 4.20 (t, 2H), 3.85 (s, 3H), 3.25 (t, 2H), 3.09 (br s, 4H), 2.59 (br s, 4H ), 2.32 (s, 3H). Example 8 79 This paper size applies Chinese National Standard (CNS) A4 (210X297 mm). Please read the notes on the back before loading.

T 訂 509687 A7 _ __ B7 五、發明説明（78 ) 2,3-二氩-(4-甲基六氩吡畊-1-基)小[4-(吡啶_4_基)萘_1基 胺基羰基)-1Η-吲哚 使用實施例4之類似方法，自4-(吡啶-4-基）萘-1-基胺 (D2)和2,3-二氫-6-(4-甲基六氫吡畊小基HH-吲哚 (D11)製備得米黃色固體標題化合物（50%)。 lH NMR (250MHz? CDC13) δ (ppm) ： 8.75-8.70 (m, 2H) ^ 7.99 (d，1H)，7.92-7.86 (m，2H)，7·75 (d，1H)，7·62-7·40 (m，5H)， 7·09 (d，1H)，6.90 (s，1H)，6.65 (dd，1H)，4·26 (t5 2H)， 3.28-3.17 (m，6H)，2.55-2.50 (m，4H)，2.32 (s，3H) 〇 實施例9 5-氣-2,3-二氩_6·(4·甲基六氩峨啼-1-基)-l-【4-(吼唆-4-基) 萘-1-基胺基羰基ΗΗ_吲哚 使用實施例4之類似方法，自4-(4_吡°定-4-基)萘-μ基胺 (D2)和5_亂_2,3_二風_6-(4_甲基六氮吼11 井-1_基)-ΐΗ-ρ引口朵 (D13)製備標題化合物（38%)。自丙酮中將其轉換成 鹽酸鹽黃色固體。 經濟部智慧財產局員工消費合作社印製 'HNMRC 自由鹼)(25〇MHz，CDCl3)S(ppm):8.73-8.67(m， 2H)，8.00 (dd，1H)，7·91-7·82 (m，3H)，7·62-7·37 (m，5H), 7·18 (s，1Η)，6·92 (s，1Η)，4·26 (t，2Η)，3·24 (t5 2Η) , 3·06 (br s，4H)，2·56 (br s，4H)，2.32 (s，3H)。 實施例10 5-淡-2,3-二氣-6-(4-甲基六氣啦喷-1-基)-1-【4~(吼唆-4-基) 萘-1-基胺基羰基】-1H-蚓哚 使用說明14之類似方法，自2,3-二氫-6-(4-甲基六氫吡畊 80 本紙張尺度適用中國國家;( CNS》(210&gt;&lt;297公釐] &quot;' 509687 A7 B7 五、發明説明（79 ) -1-基)比°定-4-基)茶-1_基胺基幾基]-1H-弓丨。朵（E8 ) 和苯甲基三甲基三溴化銨製備得米黃色固體標題化合物 (86%)。自丙酮中將此物質轉換成其鹽酸鹽黃色固體。 4 NMR (250MHz，CDC13) δ (ppm): 8.76-8.70 (m5 2H)，8.00 (d51H)，7.91-7.82 (m，3H)，7.62麵7.37 (m，6H)，6.93 (s51H)， 4.26(t，2H)，3.24 (t，2H)，3.05 (brs，4H)，2.56 (brs，4H)， 2.32 (s，3H)。 實施例11 5·漠-2,3-二氮-6-(4-甲基六氮咐喷-1-基)-1-[4-(吼咬-4-基) 萘-1_基)苯基胺基羰基】_111_弓丨哚 使用實施例4之類似方法，自4-(吡啶-4-基)萘-1-基苯胺 (D5)和5-&gt;臭-2,3-二風_6_(4_甲基六氨比σ井-1_基)-111-0弓卜朵 (D15)製備得白色固體標題化合物（24%)。 !H NMR (250MHz, CDC13) δ (ppm) ： 8.52-8.45 (m5 2H) ^ 8.00 (s，1H)，7·71 (s5 1H)，7.60-7.45 (m，4H)，7·37 (dd，2H)， 7.18 (s，1H)，4.05 (t，2H)，3.03 (t，2H)，2.92 (br s，4H)，2·45 (br s，4H)，2·20 (s，3H)。 實施例12 經濟部智慧財產局員工消費合作社印製 5-溴-1-[3·氣·4·(吡啶-4-基)苯基胺基羰基】-2,3·二氩_6_(4_ 甲基六氩吡畊-1-基)-1Η-吲哚 使用實施例4之類似方法，自3-氣-4-(吡啶-4_基）苯胺 (D6)和5_&gt;臭-2,3_二鼠_6-(4-甲基六氮〇比。井-1-基)-111-11弓卜朵 (D15)製備得白色固體標題化合物（13%)。 !H NMR (250MHz? CDCl3+d6DMSO) δ (ppm) ： 8.75 (d, 81 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 509687 A7 __B7 五、發明説明（80 ) 2H) ’ 8.40 (s，1H)，7·92 (s，1H)，7.88 (d，1H)，7.75 (dd，1H)， 7.52 (s，1H) ’ 7.42 (d，2H)，7.33 (d，1H)，4·27 (t，2H)，3.25 (t，2H) ’ 2.97 (br s，4H)，2·60 (br s，4H)，2·35 (s，3H)。 實施例13 5 2,3-二氩-5-甲基-6-(4-甲基六氣吡畊士基^小卜(吡唆基) 萘-1-基胺基羰基HH_吲哚 使用實施例4之類似方法，自4_(吡啶_4-基）萘β1_基胺 (D2)和2,3_二氫-5_甲基-6-(4-甲基六氫吡讲_1_基)-iH-吲哚（D17)製備標題化合物（52%)。自丙酮中將此物 質轉換成其鹽酸鹽黃色固體。 !HNMR(自由鹼)(250MHz，CDC13) δ (ppm): 8.73-8.70 (m， 2H)，7.98(d，lH)，7.93-7.85 (m，2H)，7.73(s，lH)，7.60· 7·48 (m，5H)，7·02 (s，1H)，6·95 (s，1H)，4·23 (t，2H)，3.22 (t，2H)，2.95-2.90 (m，4H)，2.54 (br s5 4H)，2·31 (s，3H)， 2.26(s，1H)。 實施例14 1-[3·氣-4-(吡啶-4-基)苯基胺基羰基】-2,3-二氩-5-甲基_6-(4-甲基六氩吡畊-1·基)-1Η-弓丨哚 經濟部智慧財產局員工消費合作社印製 使用實施例4之類似方法，自3-氯-4-(吡啶-4-基）苯胺 (D6)和2,3-二氫_5_甲基-6·(4-甲基六氫吡畊-1-基)-1Η-吲哚（D17)製備得白色固體標題4合物（67%)。 NMR (250MHz，d6DMSO) δ (ppm): 8.92 (s，1H)，8·80 (d， 2H)，8_08 (d，1H)，7.87-7.83 (m，2H)，7·63 (d，2H)，7.56 (d， 1H)，7.14 (s，1H)，4·27 (t，2H)，3.24 (t，2H)，2.94 (br s，4H)， 82 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 509687 A7 B7 五、發明説明（81 ) 2.65 (br s，4H)，2.38 (s，3H)，2.32 (s，3H)。 實施例15 2,3_二氩-6-(4-甲基六氩吡畊小基)小【4-(吡啶-4-基)萘-1_ 基胺基羰基卜5-乙烯基-1H-吲哚 使用實施例4之類似方法，自4-(吡啶-4-基)萘-1-基胺 (D2 )和2,3·二氫-6-(4-甲基六氫吡畊小基)-5-乙烯基-1H-吲哚（D19)製備標題化合物（5〇〇/。）。自乙酸乙酯中將 此物質轉換成其鹽酸鹽黃色固體。 !H NMR (250MHz，CDC13) δ (ppm) : 8.77-8.70 (m，2H)，8.00 (d，1H)，7.96-7.86 (m，2H)，7.76 (s，1H)，7·65-7·40 (m，5H)， 7·37 (s，1H)，7.0 (dd，1H)，6.92 (s，1H)，5.60 (dd，1H)，5.15 (dd，1H)，4.28 (t，2H)，3·29 (t，2H)，3.05-2.95 (m，4H)，2.55 (br s，4H)，2.33 (s，3H)。 實施例16 2,3·二氩-5-己基-6-(4-甲基六氩吼啡_i_基)-l-[4-(吼咬_4_基) 萘小基胺基羰基】_1H_吲哚 經濟部智慧財產局員工消費合作社印製 使用實施例4之類似方法，自4-(吡啶-4-基)萘-1-基胺 (D2)和2,3-二氫-5-乙基-6-(4-曱基六氫吡畊_1_基)-1Η-吲哚（D21)製備米黃色固體標題合物（43%)。自丙 酮中將此物質轉換成其鹽酸鹽黃色固體。 NMR (250MHz，CDC13) δ (ppm) : 8.74-8.70 (m，2H)， 8·03-7·87 (m，3H)，7·77 (s51H)，7.60-7.38 (m，5H)，7·09 (s， 1H)，6.92(s，1H)，4.26(t，2H)，3.26(t，2H)，2·98-2·92(ηι， 4H)，2.66 (q，2H)，2·61 (br s，1H)，2·36 (s，3H)，1·23 (t，3H)。 83 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） — 509687 A7 ____B7 五、發明説明（82 ) 實施例17 1-[3_氯-4_(吡啶-4-基)苯基胺基羰基】_2,3_二氩各己基_6_ (4-甲基六氩吡畊-1_基)_ 1H_吲哚 使用實施例4之類似方法，自3-氯-4-(吡啶-4-基)胺（D6) 和2,3-二氫-5-乙基-6_(4-曱基六氫ti比σ井小基)_1Η·$卜朵 (D21)製備白色固體標題化合物（33%)。 H NMR (250MHz，CDC13) δ (ppm) : 8.72-8.62 (m，2Η)， 7.73-7.65 (m，2H) ’ 7.50-7.20 (m，4H)，7·07 (s，1H)，6.60 (s， 1H)，4.09 (t，2H)，3.18(t，2H)，2.97-2.90 (m，4H)，2.66(q， 2H)，2.57 (br s，4H)，2·35 (s，3H)，1·22 (t，3H)。 實施例18 2,3-二氣-6-(4-甲基六氣啦喷-1-基)-1-【4-(峨咬-4_基)茶-1-基胺基羰基】-5-三氟甲基-1H-吲哚 使用實施例4之類似方法，自4-(吡啶-4-基)萘-1-基胺 (D2)和2,3-二氫-6_(4-甲基六氫咄畊小基)-5-三氟甲基-1H-吲哚（D23)製備米黃色固體標題化合物（42%)。自 丙酮中將此物質轉換成其鹽酸鹽黃色固體。 經濟部智慧財產局員工消費合作社印製 4 NMR (250MHz，CDC13) δ (ppm) : 8.77-8.71 (m，2H)， 8.01-7.85 (m，3H)，7·63-7·39(ιη，6Η)·，7.69(s，lH)，4.33(t， 2H)，3.32 (t，2H)，3.05_2.96(m，4H)，2.64 (brs，4H)，2·38 (s5 3H) 〇 實施例19 H3_氯冰(吡啶-4-基)苯基胺基羰基】-2,3-二氩-6-(4-甲基 六氣吡畊_1_基)-5-三氟甲基_1H-吲鳴 84 本紙張尺度適用中國國家標準（CNS ) A4規▲ ( 210 X297公釐） 509687 A7 _____— B7 五、發明説明（83 ) 使用實施例4之類似方法，自3_氣4_(吡啶-4-基)苯胺 (D6)和2,3-二氫-6-(4-甲基六氫吡畊基三氟曱基_ 1H-♦朵（D23)製備米黃色固體標題化合物（17%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.69-8.65 (m，2H)，8.05 (s，1Η)，7·67 (d，1Η) ’ 7·46 (dd，1H&gt;，7·44-7·37 (m，3H)， 7.31 (d，1H)，6.59 (s，1H)，4· 16 (t，2H)，3.27 (t，2H)，3.00-2.94 (m，4H)，2·55 (br s，4H)，2.34 (s5 3H)。 實施例20 2,3_二氩_5_甲氧基各(4-甲基六氬吡脅-l-基)小[4_(峨啶冬 基)萘-1-基6醮基】-1Η-吲哚 經濟部智慧財產局員工消費合作社印製 將乙一醯氣（206毫克’ 1.6毫莫耳）加入溶於ch2C12 (30 毫升）之經攪拌4_(吼啶_4_基)萘-1_基乙酸（D24，213毫 克，0.81毫莫耳）懸浮液，隨後以DMF(1滴）。待經2 小時後，將溶劑和過量乙二醯氯於真空中移除，獲得淺黃 色固體醯基氣。將此溶解於CH2C12 ( 10毫升），並於氬 氣下0°C時’逐份加入經攪拌2,3_二氫-5-曱氧基-6-(4-甲基 六氫11比。井-1-基)-1Η-,哚（WO 95/06627中間物，200毫 克，0.81毫莫耳）和溶於CH2C12 (15毫升）NEt3 (164毫 克，1.6毫莫耳）溶液中超過1〇分鐘。待於〇〇c下3〇分鐘 後’將此混合物於室溫下攪拌5小時，然後以1〇% NazCO^aq)洗務，乾燥（Na2S04) ’並於真空中濃縮。藉 由層析術將粗製綠色/棕色油於石夕石凝膠上以2-5% MeOH/CHzCl2溶析而純化，獲得黃色固體標題化合物（34〇 毫克，85%)。 85 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 一 · 509687 A7 B7 五、發明説明（84 ) 經濟部智慧財產局員工消費合作社印製 lH NMR (250MHz, CDC13) δ (ppm) ： 8.72 (d5 2H) ^ 8.02 (s, 1H)，8.02 (d，1H)，7.87 (d，1H)，7.37-7.60 (m，6H)，6.74 (s， 1H)，4.26 (s，2H)，4·25 (s，2H)，3.85 (s，3H)，3·22 (t，2H)， 3.08 (br s，4H)，2.57 (br s，4H)，2·32 (s，3H)。 實施例21 2,3_ 二氩-5-甲氧基-6-(4-甲基六氫 基)萘_1_基乙醢基HH-吲哚 使用實施例20之類似方法，自5-(吡啶_4_基)萘-1-基乙酸 (D25)和2,3-二氫-5-甲氧基各(4:甲基六氫吡畊小基)-1H-吲哚（WO95/06627中間物3)製備標題化合物。 !H NMR (250MHz, CDC13) δ (ppm) ： 8.72 (d5 2H) » 8.03 (d, 1H)，8.02 (s，1H)，7.78 (dd，1H)，7.59 (t，lH)，7·45·7·39 (m， 5H)，6.74 (s，1H)，4·25 (s，2H)，4.22.(t，2H)，3·84 (s，3H)， 3·20 (t，2H)，3.07 (br s，4H)，2·57 (br s，4H)，2.31 (s，3H)。 實施例22 2,3_二氩-6-(4_甲基六氫吡畊_1·基(吡咬_4_基)萘小 基乙醯基】_1H-吲哚 使用實施例20之類似方法，自4-(吼咬-4-基)萘-1-基乙酸 (D24)和2,3-二氫-6·(4-甲基六氫Li_基pH-in朵 (D11)製備標題化合物’自乙酸乙酯獲得米黃色固體 (72%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.75-8.70 (m，2H)， 8.04-7.94 (m，2H) ’ 7.88 (d，1H) ’ 7.62-7.33 (m，6H)，7·〇9 (d， 1H)，6.61 (dd，1H)，4.26 (s，2H)，4.25 (t，2H)，3.25-3.13 (m，86 (請先閲讀背面之注意事項再· 裝| 訂 線 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7五、發明説明（85 ) 經濟部智慧財產局員工消費合作社印製 6H)，2.55-2.47 (m，4H)，2.30 (s，3H)。 實施例23 5_氣-2,3_二氩-6_(4·甲基六氩吡畊小基)-1-【4-(吡啶-4-基) 萘-1-基乙醢基HEMf丨嗦 使用實施例20之類似方法，自4-(吡啶-4-基)萘-1-基乙酸 (D24)和5-氣-2,3-二氫-6-(4-甲基六氫吼。井-1-基)-1Η-吲 哚（D13)製備得黃色油標題化合物（50%)。自乙酸乙 酯中將此物質轉換成其鹽酸鹽米黃色固體。 lR NMR (250MHz? CDC13) δ (ppm) ： 8.75-8.70 (m5 2H) ^ 8.08 (s5 1H)，8·00 (d，1H)，7·88 (dd，1H)，7.65-7.35 (m，6H)， 7.19(s，1H)，4.27(t+s，2H)，3.20 (t，2H)，3.06 (brs，4H)， 2.57 (br s，4H)，2.33 (s，3H)。 實施例24 5-溴-2,3-二氩-6-(4-甲基六氩吡畊_1-基)-l-[4_(吡啶-4_基) 萘小基乙醢基】-1Η_弓丨哚 使用說明14之類似方法，自2,3-二氫-6-(4-曱基六氫吡畊 -1-基)-1-[4-(吡啶-4-基)萘-1-基乙醯基]-1H-吲哚（E22)製 備標題化合物（62%)。自乙酸乙酯中將此物質轉換成其 鹽酸鹽白色固體。 !H NMR (250MHz，CDC13) δ (ppm): 8.75-8.70 (m，2H)，8.08 (s，1Η)，8·00 (d，1Η)，7·89 (dd，1Η)，7.63-7.35 (m，7H)， 4.27 (t+s，4H)，3.20 (t，2H)，3.04 (br s，4H)，2.56 (br s，4H)， 2.32 (s，3H)。 實施例25 87 (請先閱讀背面之注意事項再 裝·T order 509687 A7 _ __ B7 V. Description of the invention (78) 2,3-Diargon- (4-methylhexapyridin-1-yl) small [4- (pyridine_4-yl) naphthalene_1yl Aminocarbonyl) -1H-indole Using a method similar to that in Example 4, from 4- (pyridin-4-yl) naphthalen-1-ylamine (D2) and 2,3-dihydro-6- (4-formaldehyde) Hexahydropyridine HH-indole (D11) prepared the title compound (50%) as a beige solid. LH NMR (250MHz? CDC13) δ (ppm): 8.75-8.70 (m, 2H) ^ 7.99 (d , 1H), 7.92-7.86 (m, 2H), 7.75 (d, 1H), 7.62-7 · 40 (m, 5H), 7.09 (d, 1H), 6.90 (s, 1H) , 6.65 (dd, 1H), 4.26 (t5 2H), 3.28-3.17 (m, 6H), 2.55-2.50 (m, 4H), 2.32 (s, 3H). Example 9 5-Gas-2, 3-Diargon-6 · (4 · methylhexaargon-1-yl) -l- [4- (suldin-4-yl) naphthalen-1-ylaminocarbonylfluorene-indole Usage Examples A similar method of 4, from 4- (4-pyridine-4-yl) naphthalene-μylamine (D2) and 5_ran_2,3_two wind_6- (4_methylhexazine 11 Well-1_base) -ΐΗ-ρ inlet (D13) prepared the title compound (38%). It was converted to the hydrochloride yellow solid from acetone. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs' HNMRC Free ) (25MHz, CDCl3) S (ppm): 8.73-8.67 (m, 2H), 8.00 (dd, 1H), 7.91-7 · 82 (m, 3H), 7.62-7 · 37 ( m, 5H), 7 · 18 (s, 1Η), 6.92 (s, 1Η), 4.26 (t, 2Η), 3.24 (t5 2Η), 3.06 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 10 5-Meta-2,3-digas-6- (4-methylhexakiolapentyl-1-yl) -1- [4 ~ (stilbene-4-yl) naphthalene-1-ylamine Carbonyl group] -1H-eardole using a similar method as described in note 14, from 2,3-dihydro-6- (4-methylhexahydropyridine 80 This paper is applicable to China; (CNS) (210 &gt; &lt; (297 mm) &quot; '509687 A7 B7 V. Description of the invention (79) -1-yl) ratio ° den-4-yl) tea-1_ylaminojiki] -1H-bow 丨 .Duo (E8) And benzyltrimethylammonium tribromide to prepare the title compound as a beige solid (86%). This material was converted to its hydrochloride yellow solid from acetone. 4 NMR (250MHz, CDC13) δ (ppm): 8.76-8.70 (m5 2H), 8.00 (d51H), 7.91-7.82 (m, 3H), 7.62 surface 7.37 (m, 6H), 6.93 (s51H), 4.26 (t, 2H), 3.24 (t, 2H), 3.05 (brs, 4H), 2.56 (brs, 4H), 2.32 (s, 3H). Example 11 5 · Mo-2,3-diazine-6- (4-methylhexazine) -1-yl ) -1- [4- (swine-4-yl) naphthalene-1_yl) phenylaminocarbonyl] _111_bendoindole Using a method similar to that in Example 4, from 4- (pyridin-4-yl) Naphthalene-1-ylaniline (D5) and 5- &gt; Odor-2,3-diwind_6_ (4_methylhexamine ratio σ well-1_yl) -111-0 Gongbuduo (D15) The title compound (24%) was prepared as a white solid. ! H NMR (250MHz, CDC13) δ (ppm): 8.52-8.45 (m5 2H) ^ 8.00 (s, 1H), 7.71 (s5 1H), 7.60-7.45 (m, 4H), 7.37 (dd , 2H), 7.18 (s, 1H), 4.05 (t, 2H), 3.03 (t, 2H), 2.92 (br s, 4H), 2.45 (br s, 4H), 2.20 (s, 3H ). Example 12 Printing of 5-Bromo-1- [3 · Ga · 4 · (Pyridin-4-yl) phenylaminocarbonyl]]-2,3 · Diargon_6_ (4_ Methylhexaargin-1-yl) -1fluorene-indole Using a similar method to that described in Example 4, from 3-gas-4- (pyridin-4-yl) aniline (D6) and 5_ &gt; _Musrat_6- (4-methylhexazine ratio. Well-1-yl) -111-11 Gongbuduo (D15) prepared the title compound (13%) as a white solid. ! H NMR (250MHz? CDCl3 + d6DMSO) δ (ppm): 8.75 (d, 81) This paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 509687 A7 __B7 V. Description of the invention (80) 2H ) '8.40 (s, 1H), 7.92 (s, 1H), 7.88 (d, 1H), 7.75 (dd, 1H), 7.52 (s, 1H)' 7.42 (d, 2H), 7.33 (d, 1H), 4.27 (t, 2H), 3.25 (t, 2H) '2.97 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 13 5 2,3-Diargon-5-methyl-6- (4-methylhexapyrazinyl ^ pyridinyl (pyridinyl) naphthalene-1-ylaminocarbonylHH_indole use A similar method to that in Example 4 was performed from 4- (pyridine_4-yl) naphthalene β1-ylamine (D2) and 2,3_dihydro-5_methyl-6- (4-methylhexahydropyridine_1 -Yl) -iH-indole (D17) to prepare the title compound (52%). This material was converted to its hydrochloride yellow solid from acetone.! HNMR (free base) (250MHz, CDC13) δ (ppm): 8.73-8.70 (m, 2H), 7.98 (d, 1H), 7.93-7.85 (m, 2H), 7.73 (s, 1H), 7.60 · 7.48 (m, 5H), 7.02 (s, 1H ), 6.95 (s, 1H), 4.23 (t, 2H), 3.22 (t, 2H), 2.95-2.90 (m, 4H), 2.54 (br s5 4H), 2.31 (s, 3H ), 2.26 (s, 1H). Example 14 1- [3-Ga-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-diargon-5-methyl-6- ( 4-Methylhexapyridine-1 · yl) -1Η-bendole printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs using a similar method as in Example 4, starting from 3-chloro-4- (pyridin-4-yl ) Aniline (D6) and 2,3-dihydro-5-methyl-6 · (4-methylhexahydropyrine-1-yl) -1Η-indole (D17) to prepare the title compound 4 as a white solid (67%). NMR (250MHz, d6DMSO) δ (ppm): 8.92 (s, 1H), 8.80 (d, 2H), 8_08 (d, 1H), 7.87-7.83 (m, 2H), 7.63 (d, 2H) , 7.56 (d, 1H), 7.14 (s, 1H), 4.27 (t, 2H), 3.24 (t, 2H), 2.94 (br s, 4H), 82 This paper standard applies to the Chinese National Standard (CNS) A4 specifications (210X 297 mm) 509687 A7 B7 V. Description of the invention (81) 2.65 (br s, 4H), 2.38 (s, 3H), 2.32 (s, 3H). Example 15 2,3_diargon- 6- (4-Methylhexylpyridinyl) small [4- (pyridin-4-yl) naphthalene-1 -ylaminocarbonylcarbonyl 5-vinyl-1H-indole Using a similar method as in Example 4, From 4- (pyridin-4-yl) naphthalen-1-ylamine (D2) and 2,3 · dihydro-6- (4-methylhexahydropyridyl) -5-vinyl-1H-ind Indole (D19) prepared the title compound (500 /.). This material was converted to its hydrochloride yellow solid from ethyl acetate.! H NMR (250MHz, CDC13) δ (ppm): 8.77-8.70 (m , 2H), 8.00 (d, 1H), 7.96-7.86 (m, 2H), 7.76 (s, 1H), 7.65-7 · 40 (m, 5H), 7.37 (s, 1H), 7.0 (dd, 1H), 6.92 (s, 1H), 5.60 (dd, 1H), 5.15 (dd, 1H), 4.28 (t, 2H), 3.29 (t, 2H), 3. 05-2.95 (m, 4H), 2.55 (br s, 4H), 2.33 (s, 3H). Example 16 2,3 · Diargon-5-hexyl-6- (4-methylhexaarginine_i_yl) -l- [4- (swine_4_yl) naphthylaminoaminocarbonyl ] _1H_Indole Printed by a consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs using a similar method as in Example 4, starting from 4- (pyridin-4-yl) naphthalene-1-ylamine (D2) and 2,3-dihydro- 5-ethyl-6- (4-fluorenylhexahydropyridin-1-yl) -1fluorene-indole (D21) prepared the title compound as a beige solid (43%). This material was converted from acetone to its hydrochloride yellow solid. NMR (250MHz, CDC13) δ (ppm): 8.74-8.70 (m, 2H), 8.03-7 · 87 (m, 3H), 7.77 (s51H), 7.60-7.38 (m, 5H), 7 09 (s, 1H), 6.92 (s, 1H), 4.26 (t, 2H), 3.26 (t, 2H), 2.98-2.92 (η, 4H), 2.66 (q, 2H), 2 · 61 (br s, 1H), 2.36 (s, 3H), 1.23 (t, 3H). 83 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) — 509687 A7 ____B7 V. Description of the invention (82) Example 17 1- [3_chloro-4_ (pyridin-4-yl) phenylamine Carbonyl] _2,3_diargon, each hexyl-6_ (4-methylhexapyridin-1_yl) -1H_indole Using a method similar to that in Example 4, from 3-chloro-4- (pyridine- 4-yl) amine (D6) and 2,3-dihydro-5-ethyl-6_ (4-fluorenylhexahydroti than σ well small group) _1Η · $ 卜 朵 (D21) to prepare the title compound as a white solid ( 33%). H NMR (250MHz, CDC13) δ (ppm): 8.72-8.62 (m, 2Η), 7.73-7.65 (m, 2H) '7.50-7.20 (m, 4H), 7.07 (s, 1H), 6.60 ( s, 1H), 4.09 (t, 2H), 3.18 (t, 2H), 2.97-2.90 (m, 4H), 2.66 (q, 2H), 2.57 (br s, 4H), 2.35 (s, 3H ), 1.22 (t, 3H). Example 18 2,3-Digas-6- (4-methylhexakiolapent-1-yl) -1- [4- (erbino-4-yl) tea-1-ylaminocarbonyl]- 5-Trifluoromethyl-1H-indole Using a similar method as in Example 4, starting from 4- (pyridin-4-yl) naphthalen-1-ylamine (D2) and 2,3-dihydro-6- (4- Methylhexahydropyrene) -5-trifluoromethyl-1H-indole (D23) to prepare the title compound (42%) as a beige solid. This material was converted from acetone to its hydrochloride yellow solid. Printed by 4th NMR (250MHz, CDC13) δ (ppm): 8.77-8.71 (m, 2H), 8.01-7.85 (m, 3H), 7.63-7 · 39 (ιη, 6Η) ·, 7.69 (s, 1H), 4.33 (t, 2H), 3.32 (t, 2H), 3.05_2.96 (m, 4H), 2.64 (brs, 4H), 2.38 (s5 3H). Example 19 H3_Chloro (pyridin-4-yl) phenylaminocarbonyl group] -2,3-Diargon-6- (4-methylhexapyridin_1-yl) -5-trifluoromethyl Base_1H-inding 84 This paper size applies Chinese National Standard (CNS) A4 regulations ▲ (210 X297 mm) 509687 A7 _____— B7 V. Description of the invention (83) Use the similar method of Example 4, since 3_qi 4- (Pyridin-4-yl) aniline (D6) and 2,3-dihydro-6- (4-methylhexahydropyridyltrifluorofluorenyl_ 1H- ♦ dol (D23) to prepare the title compound as a beige solid (17%). 4 NMR (250MHz, CDC13) δ (ppm): 8.69-8.65 (m, 2H), 8.05 (s, 1Η), 7.67 (d, 1Η) '7.46 (dd, 1H &gt; , 7.44-7.37 (m, 3H), 7.31 (d, 1H), 6.59 (s, 1H), 4.16 (t, 2H), 3.27 (t, 2H), 3.00-2.94 (m, 4H), 2.55 (br s, 4H), 2.34 (s5 3H). Example 20 2,3_diargon_5_methoxy each (4- Hexahydropyridyl-l-yl) small [4_ (eridinoyl) naphthalene-1-yl-6 fluorenyl] -1 fluorene-indole Printed by the consumer co-operative of the Intellectual Property Bureau of the Ministry of Economic Affairs, Ethyl tritium (206 mg '1.6 millimolar) was added to a stirred suspension of 4_ (amidin_4_yl) naphthalene-1_ylacetic acid (D24, 213 mg, 0.81 mmol) dissolved in ch2C12 (30 ml), followed by DMF ( 1 drop). After 2 hours, the solvent and excess ethylenedichloride were removed in vacuo to obtain a pale yellow solid tritium base gas. This was dissolved in CH2C12 (10 mL) and 0 ° C under argon Hourly 'was added by stirring 2,3_dihydro-5-fluorenyloxy-6- (4-methylhexahydro 11 ratio. Well-1-yl) -1fluorene-, indole (WO 95/06627 intermediate , 200 mg, 0.81 mmoles) and dissolved in a solution of CH2C12 (15 ml) NEt3 (164 mg, 1.6 mmoles) for more than 10 minutes. After 30 minutes at 00c, the mixture was placed in a chamber Stir for 5 hours at room temperature, then wash with 10% NazCO ^ aq), dry (Na2S04) 'and concentrate in vacuo. The crude green / brown oil was purified by chromatography on a sedite gel with 2-5% MeOH / CHz Cl2 to obtain the title compound (340 mg, 85%) as a yellow solid. 85 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) I. 509687 A7 B7 V. Description of invention (84) lH NMR (250MHz, CDC13) printed by the Intellectual Property Bureau of the Ministry of Economic Affairs Consumer Cooperatives δ (ppm ): 8.72 (d5 2H) ^ 8.02 (s, 1H), 8.02 (d, 1H), 7.87 (d, 1H), 7.37-7.60 (m, 6H), 6.74 (s, 1H), 4.26 (s, 2H ), 4.25 (s, 2H), 3.85 (s, 3H), 3.22 (t, 2H), 3.08 (br s, 4H), 2.57 (br s, 4H), 2.32 (s, 3H ). Example 21 2,3_Diargon-5-methoxy-6- (4-methylhexahydro) naphthalene_1-ylethylfluorenyl HH-indole Using a similar method to that described in Example 20, from 5- ( Pyridine_4_yl) naphthalene-1-ylacetic acid (D25) and 2,3-dihydro-5-methoxy (4: methylhexahydropyridyl) -1H-indole (WO95 / 06627 Intermediate 3) The title compound was prepared. ! H NMR (250MHz, CDC13) δ (ppm): 8.72 (d5 2H) »8.03 (d, 1H), 8.02 (s, 1H), 7.78 (dd, 1H), 7.59 (t, 1H), 7.45 7.39 (m, 5H), 6.74 (s, 1H), 4.25 (s, 2H), 4.22. (T, 2H), 3.84 (s, 3H), 3.20 (t, 2H ), 3.07 (br s, 4H), 2.57 (br s, 4H), 2.31 (s, 3H). Example 22 2,3_Diargon-6- (4-methylhexahydropyridine_1 · yl (pyridin-4-yl) naphthylpyridylethenyl] _1H-indole was similar to that used in Example 20 Method: Prepared from 4- (sound-4-yl) naphthalene-1-ylacetic acid (D24) and 2,3-dihydro-6 · (4-methylhexahydroLi-yl pH-indol (D11) The title compound 'obtained a beige solid (72%) from ethyl acetate. 4 NMR (250 MHz, CDC13) δ (ppm): 8.75-8.70 (m, 2H), 8.04-7.94 (m, 2H)' 7.88 (d, 1H) '7.62-7.33 (m, 6H), 7.09 (d, 1H), 6.61 (dd, 1H), 4.26 (s, 2H), 4.25 (t, 2H), 3.25-3.13 (m, 86 (Please read the precautions on the back first. Binding | Threading This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 509687 A7 B7 V. Description of the invention (85) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 6H), 2.55-2.47 (m, 4H), 2.30 (s, 3H). Example 23 5_Gas-2,3_Diargon-6_ (4.methylhexaarginyl) -1- [4- (Pyridin-4-yl) naphthyl-1-ylethylfluorenyl HEMf 丨 嗦 Using a similar method to that described in Example 20, 4- (pyridin-4-yl) naphthyl-1-ylacetic acid (D24) and 5 -Ga-2,3-dihydro-6- (4-methylhexahydro roulette. Well-1 -Yl) -1H-indole (D13) to prepare the title compound as a yellow oil (50%). This material was converted from ethyl acetate to its hydrochloride beige solid. LR NMR (250MHz? CDC13) δ (ppm ): 8.75-8.70 (m5 2H) ^ 8.08 (s5 1H), 8.00 (d, 1H), 7.88 (dd, 1H), 7.65-7.35 (m, 6H), 7.19 (s, 1H), 4.27 (t + s, 2H), 3.20 (t, 2H), 3.06 (brs, 4H), 2.57 (br s, 4H), 2.33 (s, 3H). Example 24 5-Bromo-2,3-di Argon-6- (4-methylhexapyridin_1-yl) -l- [4- (pyridin-4-yl) naphthylpyridinylethenyl] -1Η_archin, using a similar method as described in Note 14, From 2,3-dihydro-6- (4-fluorenylhexahydropyridin-1-yl) -1- [4- (pyridin-4-yl) naphthalen-1-ylethenyl] -1H-ind Indole (E22) prepared the title compound (62%). This material was converted to its hydrochloride white solid from ethyl acetate.! H NMR (250MHz, CDC13) δ (ppm): 8.75-8.70 (m, 2H) , 8.08 (s, 1Η), 8.00 (d, 1Η), 7.89 (dd, 1Η), 7.63-7.35 (m, 7H), 4.27 (t + s, 4H), 3.20 (t, 2H) , 3.04 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 25 87 (Please read the precautions on the back before loading ·

、1T -線 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） I509687 A7 ________ B7五、發明説明（86 ) 經濟部智慧財產局員工消費合作社印製 2,3_二氩-6-(4-甲基六氬吡畊_1_基)小【4_(吡啶_4_基)萘小 基乙醢基】-5_乙烯基-1H-吲哚 使用實施例20之類似方法，自4-(吡啶-4-基)萘-1-基乙酸 (D24)和2,3-二氫_6-(4-甲基六氫σ比n井小基)·5_乙稀基一 1Η_吲哚（D19)和苯甲基三甲基三溴化銨製備標題化合 物（45%)。自丙酮/乙酸乙酯中將此物質轉換成其鹽酸 鹽白色固體。 HNMR(自由驗）（250MHz，CDC13) δ (ppm): 8.75-8.68 (m， 2H)，8·05-7·96(πι，2Η)，7.88(d，lH)，7.65_7.30(m，7H)， 7·00 (dd，1Η)，5·60 (dd，1Η)，5·15 (dd，1Η)，4·28 (s，2Η)， 4·26 (t，2H) ’ 3.22 (t，2H) ’ 2·98_2·91 (m，4H) ’ 2·52 (br s 4H)， 2.31(s，3H)。 ’ 實施例26 5-淡_2,3_—氮_6·(1_甲基六氬吼命小基)小【4_(吼唆_4_基) 萘小基胺基羰基HH_吲哚 使用類似於實施例4之方法，自4-(吡啶-4-基)茶_丨_基胺 (D2)和5-溴-2,3-二氫-6-(1-甲基六氫π比u井冰基)_1H^引口朵 (D39)製備標題化合物（11%)。 ” lH NMR (250MHz，d6DMSO) δ (ppm): 8.95 (s，1Η)，8 78 (dd 2H)，8·19 (dd，1H)，7·93 (m51H)，7.85 (dd，1H)，7.54-7.69 (m，6H)，7.46 (s，1H)，4·37 (t，2H)，3.27 (t，2H)，2·95 (br d， 2H)，2.82 (m，1H)，2.27 (s，3H)，2.10 (m，2H)，1 奶（m，4H)。 實施例27 5 氣-2,3-二氮-6-(4•甲基六氩吼呀-l-基)-1-[5_(吼咬_4_基) 88 (請先閱讀背面之注意事項再 -裝· I) 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇χ297公釐） 509687 Μ Α7 Β7 五、發明説明（87 經濟部智慧財產局員工消費合作社印製 萘-1-基胺基羰基】_1H_喵哚 使用類似於實施例2之方法，自5-(吡啶-4-基)萘-1-基異氰 酸酉旨（D4)和5-氣-2,3-二鼠-6-(4-甲基六氮吼11 井-1-基)-1Η_ 吲哚（D13)製備標題化合物。 4 NMR (250MHz，CDC13) δ (ppm) : 8.73 (d，2H)，8.02 (d， 1Η)，7.83 (s，1Η)，7.74 (d，lH)，7·70 (d，1H)，7.59 (t，1H)， 7·59 (t，1H)，7.47-7.40 (m，4H)，7.17 (s，1H)，6.86 (s，1H)， 4.27(t52H)，3.25 (t，2H)，3.11 (brd，4H)，2.66(brs，4H)， 2.38 (s，3H)。 實施例285_溴-2,3-二氩_6_(4-甲基六氩吡畊-1-基)·1·[5_(吡啶·4·基） 萘_1_基胺基羰基】-1Η_吲嗦 使用類似於實施例2之方法’自5-(ϋ比唆-4-基)茶-1-基異氰 酸酉旨（D4)和5-&gt;臭-2,3-二氮-6_(4-甲基六氮吼11 井-1_基)-1Η_ 吲哚（D15)製備標題化合物。 lH NMR (250MHz, CDC13) δ (ppm) ： 8.73 (d5 2H) ^ 8.02 (d5 1H)，7.84 (s，1H)，7.75 (d，1H)，7.72 (d，1H)，7.59 (t，1H)， 7.50-7.44 (m，2H)，7.41 (d，2H)，7.37 (s，1H)，6.78 (s，1H)， 4.27(t，2H)，3.26(t，2H)，2.97 (brs，4H)，2.56 (brs，4H)， 2·32 (s，3H)。 實施例29 2,3-二氮-5_甲氣基-6-(4-甲基六氮吼喷-1-基)-l_(咬琳-6·基 胺基羰基)·1Η-吲嗝 使用實施例2之類似方法，自喳啉-6-基異氰酸酯（D26) 請 先 閱 讀 背 面 之 注 意 事 項 再 b 頁 裝 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 509687 A7 B7 五、發明説明（88 ) 經濟部智慧財產局員工消費合作社印製 和2,3-二氮-5_甲氧基-6-(4-甲基六氮p比。井-1-基)-111-0引口朵 (WO95/06627中間物3)製備標題化合物。 4 NMR (250MHz，CDC13) δ (ppm) : 8.78 (dd，lH)，8.19 (d5 1Η)，8·13 (dd，1Η)，8·03 (d，1Η)，7·73 (s，1Η)，7·58 (dd，1H)， 7.37 (dd，1H)，6.83 (s，.lH)，6.74 (s，lH)，4.13(t，2H)，3.84 (s，3H)，3.20 (t，2H)，3.16 (brs，4H)，2.66 (brs，4H)，2.37 (s? 3H) 〇 實施例30 第三-丁氡基幾基胺基)苯基叛基胺基]_5-氣-2,3-二氩 -6 - (4-甲基六氩吡畊_1基)-1Η-吲嗦. 使用實施例4之類似方法，自4-(第三-丁氧基羰基胺基） 苯胺（D40 )和5-亂-2,3-二風-6-(4-曱基六鼠11比σ井-1-基)-1Η_ 吲哚（D13)製備標題化合物（29%)。 lR NMR (250MHz? CDC13) δ (ppm) ： 9.25 (s? 1H) ^ 8.45 (s? 1H)，7·78 (s，1H)，7·40 (m，4H)，7.22 (s，1H)，4·12 (t，2H)， 3·11 (t，2H)，2.98 (m，4H)，2.50 (m，4H)，2.25 (s，3H)，1·48 (s，9H)。 實施例31 5-溴-2,3_二氩-6_(4_甲基六氫吡畊_1-基)-1-(喳啉-6-基胺基 羰基)_1Η-Θ丨哚 使用實施例2之類似方法，自喳啉-6-基異氰酸酯（D26) 和5- &gt;臭_2,3_二氮-6-(4-甲基六氮^^-1-基)-1Η- 0引11 朵 (D1S)製備標題化合物。 'HNMR (250MHz, CDC13) δ (ppm) ： 8.82(dd,lH) ^ 8.17 (d, 90 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 請 閱 讀 背 面 之 注 意 事 項 再 頁 裝 訂 線 509687 A7 B7 五、發明説明（89 ) 經濟部智慧財產局員工消費合作社印製 1H)，8.13 (dd，1Η)，8·05 (d，1Η)，7·85 (s，1H)，7.57 (dd，1H)， 7·39 (t，1Η)，7·36 (s，1Η)，6·62 (s，1Η)，4·16 (t，2Η)，3·22 (t，2H)，3·12 (t，4H)，2.63 (br s，4H)，2·37 (s，3H)。 實施例326-澳-7-(4-甲基六氮峨讲-1-基)-1-【4-(峨唆-4-基)茶-1-基按 基羰基]-1，2,3,4-四氩喳啉 使用實施例4之類似方法，自4-(吡啶-4-基)萘-1-基胺 (D2)和臭-7-(4-甲基六氮11比啡-1-基)-1，2,3,4-四鼠奎咐 (D33)製備標題化合物。 'HNMR (250MHz5 CDC13) δ (ppm) ： 8.72(dd52H) ^ 8.07 (d, 1H)，7.86 (dd，1H)，7.67 (dd，1H)，7·51 (s，1H)，7.47-7.40 (m，6H)，7.26 (s，1H)，3.89 (t，2H)，3.03 (t，4H)，2·81 (t，2H)， 2.56 (t5 4H)，2.31 (s5 3H)，2.03 (五重峰，2H)。 實施例335-氣-2,3-二氩-6-(4-甲基六氮吼讲-1-基)-1-(4-苯氧基苯基 胺基羰基)·1Η_弓丨鳴 使用實施例2之類似方法，自5-氣-2,3-二氫-6·(4-甲基六 氫吡畊-1-基)-1-吲哚（D13)和4-苯氧基苯基異氰酸酯製 備標題化合物。 !HNMR(250MHz，CDC13)δ (ppm) : 7.81 (s，1H)，7.38-7.28 (m，4H)，7.13 (s，1H)，7.10-6.96 (m，5H)，6·43 (s，1H)，4·04 (t，2H)，3·15 (t，2H)，3.08 (br s，4H)，2·58 (br s，4H)，2·33 (s，3H” 實施例34 91 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 請 先 閱 讀 背 面 之 注 意 I 頁 裝 訂 線 509687 A7 -------五、發明説明（90 ) 經濟部智慧財產局員工消費合作社印製 5_氣-1_[4_(4-氣苯氧基)苯基胺基羰基】_2,3_二氩_6_(4甲 六氩吡畊_1·基)-1Η-吲哚 I使用實施例4之類似方法，自5_氯_2,3_二氳_6_(4_甲基六 氫吡畊-1-基)-1H-吲哚（D13)和4-(4-氯苯氧基)笨胺製^ 標題化合物。 lH NMR (250MHz, CDC13) δ (ppm) ： 7.81 (s5 1H) ^ 7.38 (d 2H)，7·26 (d，2H)，7.14 (s，1H)，6·98 (d，2H)，6.91 (d，2H)，5 6.41 (s，1H)，4.08 (t，2H)，3.18 (t，2H)，3.09 (brs，4H)，2別 (br s，4H)，2.35 (s，3H)。 ’ 實施例35 5-氯-2,3_二氩-6-(4-甲基六氣吡畊+基)士㈣啉+基联基 羰基)-1Η-吲哚 使用實施例2之類似方法，自喳啉-·6-基異氰酸酯和5_氯_ 2,3-二氫-6-(4-甲基六氫吼啡-1-基朵（DI3)和製備 標題化合物。 !HNMR (250MHz, CDC13) δ (ppm) ： 8.79 (dd51H) ^ 8.18 (dd 1H)，8.03 (d，1H)，7.85 (s，1Η)，7·59 (dd，1Η)，7·38 (dd，1H)， 7. 15 (s，1H)，6·90 (s，1H)，4·15 (t，2H)，3.19 (t，2H)，3.15 (br s，4H)，2·67 (br s，4H)，2.39 (s，3H)。 實施例36 S_氣-2,3-二氩_6_(4-甲基六氩吡畊_1-基)-1-(3-苯氡基苯基 胺基羰基)_1Η·吲哚 使用實施例4之類似方法’自5-氣-2,3-二氫-6-(4-甲基六 氫吡畊-1-基)-1Η-吲哚（D13)和3-苯氧基苯胺製備標題 92 f請先閲讀背面之注意事項再填頁) -裝- 訂 線· 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐1 6 9 ο A7 B7 五、發明説明（91 ) 經濟部智慧財產局員工消費合作社印製 化合物。 !H NMR (250MHz? CDC13) δ (ppm) ： 7.77 (s5 1H) &gt; 7.36-6.96 (m，9H)，6·71 (ddd，1H)，6.46 (s，1H)，4·03 (t5 2H)，3·13 (t， 2H)，3.08 (br s，4H)，2.60 (br s，4H)，2.35 (s，3H)。 實施例37 5-氣_2,3·二氩-6_(4-甲基六氩吡畊·1_基)_1-[4·(嘧啶-2-基) 苯基按基叛基】-1Η-弓丨鳴 使用實施例2之類似方法，自5-氯-2,3-二氫-6-(4-甲基六 氫吡畊-1_基)-111-吲哚（D13)和4-(嘧啶-2-基)苯基異氰酸 酯製備標題化合物，獲得淺奶油色粉末（69%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.78 (d，2H)，8.40 (d， 2H)，7·83 (s，1H)，7·60 (d，2H)，7.15 (m，2H)，6·56 (s，1H)， 4.12 (t，2H)，3.18 (t，2H)，3.18 (t，2H)，3·11 (brs，4H)，2·60 (br s，4H)，2.35 (s，3H)。 實施例38 1-(3-苄氧基苯基胺基羰基)-5-氯-2,3-二氩-6-(4-甲基六氩 吡啡_1_基)-1Η-吲哚 使用實施例4之類似方法，自3-胺基二苯甲酮和5-氣-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D13)和製備標 題化合物。 !H NMR (250MHz? CDC13) δ (ppm) ： 7.88 (m51H) ^ 7.78-7.74 (m，4H)，7.57 (d，1H)，7.49-7.40 (m，4H)，7· 11 (s，1H)，6.95 (s5 1H)，4.10 (t，2H)，3.16-3.04 (m，6H)，2.63(s，4H)，2.37 (s，3H) 〇 93 (請先閲讀背面之注意事項再 裝| 、1Τ 線 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 509687 A7 B7 五、發明説明（92 ) 經濟部智慧財產局員工消費合作社印製 實施例39 1 _(4_节氧基苯基胺基擬基)_5_氯-2,3_二氩-6_(4_甲基六氩 吡畊-1_基)·1Η-蚓唏 使用實施例4之類似方法，自4-胺基二苯曱酮和5-氣-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D13)和製備標 題化合物。 4 NMR (250MHz，CDC13) δ (ppm): 7.81-7.74 (m，5Η)，7·58 (m，1H)，7·56 (d，2H)，7.47 (t，2H)，7.13 (s，1Η)，6·85 (s， 1H)，4.10 (t，2H)，3·15 (t，2H)，3.09 (br s，4H)，2.59 (br s， 4H)，2.35 (s，3H)。 實施例40 5-氯·2,3-二氩-6-(4-甲基六氫吡畊-1-基)·1_(2_甲基喳啉-6_ 胺基羰基)_1H_吲哚 使用實施例4之類似方法，自6-胺基-2-曱基喳咁和5-氯 2,3_二氫-6_(4-甲基六氫吡畊-1-基)-1H-吲哚（D13)和製 備標題化合物。 lR NMR (250MHz, CDC13) δ (ppm) ： 8.05 (d5 1H) ^ 7.93 (d, 1H) 7.83 (s，1H)，7.54 (dd，1H)，7.22 (d，1H)，7·12 (s，1H)， 6.75 (s，1H)，4·07 (t，2H)，3.16-3.09 (m，6H)，2.70 (s，3H)， 2.61 (brs，4H)，2.35 (s，3H)。 實施例41 5-氯-2,3-二氩_1-[4-(呋喃-2_基)苯基胺基羰基】_6-(4-甲基 六氬吡畊小基)·1Η-吲哚 使用說明2之類似方法，自5-氣-2,3-二氫-1-(4-碘苯基胺 94 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）、 1T-The paper size of the paper is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) I509687 A7 ________ B7 V. Description of the invention (86) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 2,3_Diargon-6 -(4-methylhexapyridin_1-yl) small [4- (pyridin_4_yl) naphthyl small ethylacetinyl] -5_vinyl-1H-indole Using a similar method to that in Example 20, From 4- (pyridin-4-yl) naphthalen-1-ylacetic acid (D24) and 2,3-dihydro-6- (4-methylhexahydroσσ than n-well small group) -5_ethenyl-1 1Η-indole (D19) and benzyltrimethylammonium bromide produced the title compound (45%). This material was converted from acetone / ethyl acetate to its hydrochloride salt as a white solid. HNMR (free test) (250MHz, CDC13) δ (ppm): 8.75-8.68 (m, 2H), 8.05-7.96 (π, 2Η), 7.88 (d, 1H), 7.65_7.30 (m , 7H), 7.00 (dd, 1Η), 5.60 (dd, 1Η), 5.15 (dd, 1Η), 4.28 (s, 2Η), 4.26 (t, 2H) '3.22 (t, 2H) '2.98_2 · 91 (m, 4H)' 2.52 (br s 4H), 2.31 (s, 3H). '' Example 26 5-Ethyl-2,3_-nitrogen-6 (1-methylhexaarginol small group) small [4_ (arsenyl_4_yl) naphthalene small amine carbonyl HH_indole use Similar to the method of Example 4, the ratio of 4- (pyridin-4-yl) tea_ 丨 _ylamine (D2) and 5-bromo-2,3-dihydro-6- (1-methylhexahydroπ (U well ice-based) _1H ^ mouth flower (D39) to prepare the title compound (11%). ”LH NMR (250MHz, d6DMSO) δ (ppm): 8.95 (s, 1Η), 8 78 (dd 2H), 8.19 (dd, 1H), 7.93 (m51H), 7.85 (dd, 1H), 7.54-7.69 (m, 6H), 7.46 (s, 1H), 4.37 (t, 2H), 3.27 (t, 2H), 2.95 (br d, 2H), 2.82 (m, 1H), 2.27 (s, 3H), 2.10 (m, 2H), 1 milk (m, 4H). Example 27 5 Gas-2,3-diazine-6- (4 • methylhexaargine-l-yl) -1- [5_ (Roaring bite_4_Base) 88 (Please read the precautions on the back before you install-I) The size of the paper used in this edition applies to the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 509687 Μ Α7 Β7 V. Description of the invention (87 Naphthyl-1-ylaminocarbonyl group printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs) _1H_Meridine was similar to that used in Example 2 from 5- (pyridin-4-yl) Preparation of naphthalene-1-yl isocyanate (D4) and 5-gas-2,3-dimur-6- (4-methylhexaazine 11 well-1-yl) -1Η_ indole (D13) Title compound: 4 NMR (250MHz, CDC13) δ (ppm): 8.73 (d, 2H), 8.02 (d, 1Η), 7.83 (s, 1Η), 7.74 (d, 1H), 7.70 (d, 1H) ), 7.59 (t, 1H), 7.59 (t, 1H), 7.47-7.40 (m, 4H), 7.17 (s, 1H), 6.8 6 (s, 1H), 4.27 (t52H), 3.25 (t, 2H), 3.11 (brd, 4H), 2.66 (brs, 4H), 2.38 (s, 3H). Example 285_Bromo-2,3- Diargon-6- (4-methylhexapyridin-1-yl) · 1 · [5_ (pyridine · 4 · yl) naphthalene_1-ylaminocarbonyl] -1Η-indene was used similarly to Example 2 Method 'from 5- (fluorene-4-yl) tea-1-yl isocyanate (D4) and 5- &gt; odor-2,3-diaza-6_ (4-methylhexaaza Hou 11 well-1_yl) -1Η_indole (D15) to prepare the title compound. LH NMR (250MHz, CDC13) δ (ppm): 8.73 (d5 2H) ^ 8.02 (d5 1H), 7.84 (s, 1H), 7.75 (d, 1H), 7.72 (d, 1H), 7.59 (t, 1H), 7.50-7.44 (m, 2H), 7.41 (d, 2H), 7.37 (s, 1H), 6.78 (s, 1H) , 4.27 (t, 2H), 3.26 (t, 2H), 2.97 (brs, 4H), 2.56 (brs, 4H), 2.32 (s, 3H). Example 29 2,3-Diaza-5-methylamino-6- (4-methylhexazine-1-1-yl) -l- (quinolin-6-ylaminocarbonyl) · 1Η-indazole Using a similar method as in Example 2, since perylene-6-yl isocyanate (D26), please read the precautions on the back before binding on page b. The paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 509687 A7 B7 V. Description of the invention (88) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs and 2,3-diaza-5_methoxy-6- (4-methylhexaaza p ratio. Well-1-based ) -111-0 (WO95 / 06627 Intermediate 3) to prepare the title compound. 4 NMR (250MHz, CDC13) δ (ppm): 8.78 (dd, 1H), 8.19 (d5 1Η), 8.13 (dd, 1Η), 8.03 (d, 1Η), 7.73 (s, 1Η) ), 7.58 (dd, 1H), 7.37 (dd, 1H), 6.83 (s, .1H), 6.74 (s, 1H), 4.13 (t, 2H), 3.84 (s, 3H), 3.20 (t , 2H), 3.16 (brs, 4H), 2.66 (brs, 4H), 2.37 (s? 3H) 〇 Example 30 Third-butyridinyl-chitylamino) phenyl tetamino group] _5-Gas-2, 3-Diargon-6- (4-methylhexapyridinyl-1-yl) -1Η-indionium. Using a similar method to that in Example 4, from 4- (third-butoxycarbonylamino) aniline ( D40) and 5-ran-2,3-diwind-6- (4-fluorenylhexarat 11 to σ-well-1-yl) -1Η-indole (D13) to prepare the title compound (29%). lR NMR (250MHz? CDC13) δ (ppm): 9.25 (s? 1H) ^ 8.45 (s? 1H), 7.78 (s, 1H), 7.40 (m, 4H), 7.22 (s, 1H) , 4.12 (t, 2H), 3.11 (t, 2H), 2.98 (m, 4H), 2.50 (m, 4H), 2.25 (s, 3H), 1.48 (s, 9H). Example 31 5-Bromo-2,3-diargon-6_ (4-methylhexahydropyridine_1-yl) -1- (fluorin-6-ylaminocarbonyl) _1Η-Θ A similar method as in Example 2 was obtained from perylene-6-yl isocyanate (D26) and 5- &gt; odor_2,3_diaze-6- (4-methylhexaaza ^^-1-yl) -1Η- The title compound was prepared from 11 (D1S). 'HNMR (250MHz, CDC13) δ (ppm): 8.82 (dd, lH) ^ 8.17 (d, 90) This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm) Please read the notes on the back and bind it again Line 509687 A7 B7 V. Description of the invention (89) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 1H), 8.13 (dd, 1Η), 8.05 (d, 1Η), 7.85 (s, 1H), 7.57 (dd, 1H), 7.39 (t, 1Η), 7.36 (s, 1Η), 6.62 (s, 1Η), 4.16 (t, 2Η), 3.22 (t, 2H) , 3.12 (t, 4H), 2.63 (br s, 4H), 2.37 (s, 3H). Example 326-Ao-7- (4-methylhexaazolone-1-yl) -1- [4- (erim-4-yl) tea-1-ylylcarbonyl] -1,2, 3,4-Tetraarginoline was used in a similar manner to Example 4, starting from 4- (pyridin-4-yl) naphthalen-1-ylamine (D2) and odorant 7- (4-methylhexaazine 11 (1--1-yl) -1,2,3,4-tetramidine (D33) to prepare the title compound. 'HNMR (250MHz5 CDC13) δ (ppm): 8.72 (dd52H) ^ 8.07 (d, 1H), 7.86 (dd, 1H), 7.67 (dd, 1H), 7.51 (s, 1H), 7.47-7.40 ( m, 6H), 7.26 (s, 1H), 3.89 (t, 2H), 3.03 (t, 4H), 2.81 (t, 2H), 2.56 (t5 4H), 2.31 (s5 3H), 2.03 (five Heavy peak, 2H). Example 335-Gas-2,3-Diargon-6- (4-methylhexaazine-1-yl) -1- (4-phenoxyphenylaminocarbonyl) Using a method similar to that in Example 2, from 5-gas-2,3-dihydro-6 · (4-methylhexahydropyrine-1-yl) -1-indole (D13) and 4-phenoxy Phenyl isocyanate prepared the title compound. ! HNMR (250MHz, CDC13) δ (ppm): 7.81 (s, 1H), 7.38-7.28 (m, 4H), 7.13 (s, 1H), 7.10-6.96 (m, 5H), 6.43 (s, 1H), 4.04 (t, 2H), 3.15 (t, 2H), 3.08 (br s, 4H), 2.58 (br s, 4H), 2.33 (s, 3H) Example 34 91 This paper size applies to Chinese National Standards (CNS) A4 (210 X 297 mm) Please read the note on the back page I. Binding line 509687 A7 ------- V. Description of invention (90) Intellectual property of the Ministry of Economic Affairs 5_ 气 -1_ [4_ (4-Gaphenoxy) phenylaminocarbonyl group] printed by the Bureau ’s Consumer Cooperatives] _2,3_diargon_6_ (4methylhexapyridine_1 · yl) -1Η- Indole I was used in a similar manner to Example 4 from 5-chloro_2,3_diamidino_6_ (4-methylhexahydropyridin-1-yl) -1H-indole (D13) and 4- ( 4-chlorophenoxy) benzylamine ^ Title compound. LH NMR (250MHz, CDC13) δ (ppm): 7.81 (s5 1H) ^ 7.38 (d 2H), 7.26 (d, 2H), 7.14 (s , 1H), 6.98 (d, 2H), 6.91 (d, 2H), 5 6.41 (s, 1H), 4.08 (t, 2H), 3.18 (t, 2H), 3.09 (brs, 4H), 2 Be (br s, 4H), 2.35 (s, 3H). Example 35 5-Chloro-2,3-diargon-6- (4-methylhexapyridine + Yl) stilbene + hydrasylcarbonyl) -1 stilbene-indole Using a similar method as in Example 2, starting from stilbene-6 -Methylhexahydro-1-ynyl (DI3) and preparation of the title compound.! HNMR (250MHz, CDC13) δ (ppm): 8.79 (dd51H) ^ 8.18 (dd 1H), 8.03 (d, 1H), 7.85 (s, 1Η), 7.59 (dd, 1Η), 7.38 (dd, 1H), 7. 15 (s, 1H), 6.90 (s, 1H), 4.15 (t, 2H ), 3.19 (t, 2H), 3.15 (br s, 4H), 2.67 (br s, 4H), 2.39 (s, 3H). Example 36 S_Gas-2,3-Diargon_6_ ( 4-methylhexahydropyridine_1-yl) -1- (3-phenylfluorenylphenylaminocarbonyl) _1Η · indole Using a similar method to that described in Example 4 'from 5-Gas-2,3-di Hydrogen-6- (4-methylhexahydropyridin-1-yl) -1Η-indole (D13) and 3-phenoxyaniline to prepare the title 92 f Please read the notes on the back before filling in the page)- -Alignment · This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm 1 6 9 ο A7 B7) 5. Description of the invention (91) Compounds printed by employees of the Intellectual Property Bureau of the Ministry of Economic Affairs. ! H NMR (250MHz? CDC13) δ (ppm): 7.77 (s5 1H) &gt; 7.36-6.96 (m, 9H), 6.71 (ddd, 1H), 6.46 (s, 1H), 4.03 (t5 2H), 3.13 (t, 2H), 3.08 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 37 5-Gas_2,3 · Diargon-6_ (4-methylhexapyridine · 1-yl) _1- [4 · (Pyrimidin-2-yl) phenylatomyl] -1Η -Gongming Using a method similar to that in Example 2, from 5-chloro-2,3-dihydro-6- (4-methylhexahydropyridine-1_yl) -111-indole (D13) and 4 -(Pyrimidin-2-yl) phenyl isocyanate to prepare the title compound, obtaining a light cream-colored powder (69%). 4 NMR (250MHz, CDC13) δ (ppm): 8.78 (d, 2H), 8.40 (d, 2H), 7.83 (s, 1H), 7.60 (d, 2H), 7.15 (m, 2H) , 6.56 (s, 1H), 4.12 (t, 2H), 3.18 (t, 2H), 3.18 (t, 2H), 3.11 (brs, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 38 1- (3-Benzyloxyphenylaminocarbonyl) -5-chloro-2,3-diargon-6- (4-methylhexapyridin_1-yl) -1fluorene-indole Using a similar method as in Example 4, from 3-aminobenzophenone and 5-gas-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1Η-indole (D13) and preparation of the title compound. ! H NMR (250MHz? CDC13) δ (ppm): 7.88 (m51H) ^ 7.78-7.74 (m, 4H), 7.57 (d, 1H), 7.49-7.40 (m, 4H), 7.11 (s, 1H ), 6.95 (s5 1H), 4.10 (t, 2H), 3.16-3.04 (m, 6H), 2.63 (s, 4H), 2.37 (s, 3H) 〇93 (Please read the precautions on the back before reinstalling | 1. The paper size of the 1T line paper applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 509687 A7 B7 V. Description of the invention (92) Example 39 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1 _ (4_section Oxyphenylamino peptidyl) -5_chloro-2,3_diargon-6_ (4-methylhexaargin-1_yl) · 1Η-wormworm Using a similar method as in Example 4, since 4 -Aminobenzophenone and 5-Ga-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1fluorene-indole (D13) and the title compound were prepared. 4 NMR (250MHz, CDC13) δ (ppm): 7.81-7.74 (m, 5Η), 7.58 (m, 1H), 7.56 (d, 2H), 7.47 (t, 2H), 7.13 (s, 1Η) , 6.85 (s, 1H), 4.10 (t, 2H), 3.15 (t, 2H), 3.09 (br s, 4H), 2.59 (br s, 4H), 2.35 (s, 3H). Example 40 5-Chloro-2,3-diargon-6- (4-methylhexahydropyrine-1-yl) 1- (2-methyl Fluoroline-6-aminocarbonyl) _1H_indole Using a method similar to that in Example 4, from 6-amino-2-fluorenylfluorene and 5-chloro2,3_dihydro-6_ (4-methylhexade Hydropyrin-1-yl) -1H-indole (D13) and preparation of the title compound. LR NMR (250MHz, CDC13) δ (ppm): 8.05 (d5 1H) ^ 7.93 (d, 1H) 7.83 (s, 1H ), 7.54 (dd, 1H), 7.22 (d, 1H), 7.12 (s, 1H), 6.75 (s, 1H), 4.07 (t, 2H), 3.16-3.09 (m, 6H), 2.70 (s, 3H), 2.61 (brs, 4H), 2.35 (s, 3H). Example 41 5-Chloro-2,3-diargon_1- [4- (furan-2-yl) phenylamine Carbonyl group] 6- (4-methylhexapyridinyl) · 1 吲 -indole Using a similar method as described in Note 2, from 5-gas-2,3-dihydro-1- (4-iodophenylamine 94 This paper size applies to China National Standard (CNS) A4 (210X297 mm)

严J 8 6 9 A7 B7五、發明説明（93 ) 經濟部智慧財產局員工消費合作社印製 基羰基)-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D43)和2-呋喃硼酸製備標題化合物，獲得淺米色粉末（64%)。 NMR (250MHz，d6DMSO) δ (ppm) : 8.68 (s，1H)，7·82 (s， 1Η)，7.73 (d，lH)，7·76 (s，4Η)，7.25 (s，1Η)，6.86 (d，1Η)， 6.61 (dd，1H)，4.18 (t，2H)，3.15 (t，2H)，2.95 (br s，4H)， 2·26 (s，3H)。2xCH2訊號受到DMSO訊號遮蔽。 實施例425-氣-2,3-二氮-6-(4-甲基六氮吼喷-1-基)_1_[4-(嗓吩-2_基） 苯基胺基羰基]·1Η·吲嗦 使用說明2之類似方法，自5-氣-2,3-二氫小(4-碘苯基胺 基羰基)-6_(4-甲基六氫吡。井-1-基)-1Ή-吲哚（D43)和2-噻吩硼酸製備標題化合物，獲得奶油色粉末（56%)。 !H NMR (250MHz, CDC13) δ (ppm) ： 7.82 (s5 1H) ^ 7.58 (d, 2H)，7.42 (d，2H)，7.24 (d，2H)，7.14 (s，1H)，7.08 (m，1H)， 6.45(s，1H)，4.09 (t，2H)，3.18(t，2H)，3.10 (brs，4H)，2.60 (br s，4H)，2.35 (s，3H)。 實施例435-氣-2,3-二氮-6-(4-甲基六氮吼讲-1-基)-1-[5_(吼咬-4-基) 萘小基乙醮基】-1EM!丨哚 使用實施例20之類似方法，自5-(吡啶-4-基)萘-1-基乙酸 (D25 )和5-氣-2,3-二風-6-(4-甲基六氮吼11 井_1_基弓丨 哚（D13)製備標題化合物。 NMR (250MHz? CDC13) δ (ppm) ： 8.73 (dd5 2H) ^ 8.07 (s, 1H)，8.01 (d，1H)，7.79 (dd，1H)，7..61 (dd，1H)，7.45-7.41 95 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填HI頁) 裝· 訂 線 8 6 9 A7 B7 五、發明説明（94 ) (m，5H)，7· 19 (s，1H)，4.27 (s，2H)，4·26 (t，2H)，3· 19 (t，2H)， 3.05 (br s，4H)，2.56 (br s，4H)，2.32 (s，3H)。 實施例44 5-澳 _2,3-二氮 _6-(4_ 甲基六氣1基)_1-[5_(吼唆 基) 萘小基乙醢基】-1Η-吲哚 使用實施例20之類似方法，自5-(吡啶-4-基)萘-1·基乙酸 (D25 )和5-&gt;臭-2,3-二氮-6-(4-甲基六氮〇比〇井-1-基)_111-口引 哚（D15)製備標題化合物。 NMR (250MHz，CDC13) δ (ppm) : 8·73 (d，2H)，8.08 (s， 1H)，8·00(d，1H)，7·78(dd，1H)，7··60(dd，lH)，7·44-7·41 (m，5H)，7.37 (s，1H)，4.26 (s，2H)，4.25 (t5 2H)，3· 18 (t，2H)， 3.03 (br s，4H)，2.56 (br s，4H)，2.32 (s，3H)。 實施例45 5-氣_2,3-二氩甲基六氩吡畊-4-基)萘小基胺基羰 基1_6-(4_甲基六氩吡畊-1·基)-1Η-弓丨哚 使用實施例4之類似方法，自4-(1-甲基六氫吡畊-4-基)萘 -1-基胺（D46)和5-氣-2,3-二氮-6-(4-甲基六氮咐11 井-1-基)-1H-吲哚（D13)製備標題化合物。 4 NMR (250MHz，d6DMSO) δ (ppm) : 11.06 (br s，1H)， 10.94 (br s，1H)，8.82 (s，1Η)，8·27 (dd，1H)，7.78 (s，1H)， 7.63 (m，2H)，7.54 (d，1H)，7·42 (d，1H)，7.33 (s，1H)，4.30 (t，部份被遮蔽，2H)，3·74 (m，1H)，3.24 (t，2H)，3.60-2.96 (m，12H)，2.84 (s，3H)，2.83 (s，3H)，2·18 (m，4H)。 實施例46 96 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） I -----------裝 I I (請先閱讀背面之注拳項再填 1¾頁) 訂 線- 經濟部智慧財產局員工消費合作社印製 509687 A7 B7 五、發明説明（95 ) 經濟部智慧財產局員工消費合作社印製 5-氣-2,3-二氩小【4_0甲基噚嗅-4_基)笨基胺基援基]-6-(4-甲基六氩吡畊士基)-1Η_吲哚 使用實施例4之類似方法，自4-(4-甲胺基苯基)-2-甲基4 唾（D47)和5-氯-2,3_二氫-6-(4_甲基六氫。比啡_1_基)-lH-吲哚（D13)製備得淺黃色粉末標題化合物（67%)。 4 NMR (250MHz，d6DMSO) δ (ppm): 8.61 (s，1H)，8.30 (s， 1Η)，7·74 (s，1H)，7·57 (dd5 4H)，7.21 (s，1H)，4·13 (t，2H)， 3.08 (m，6H)，2.57 (s，3H)，2·38 (s，3H)。2xCIMil號受到 H20訊號遮蔽。 實施例475-溴_2,3·二氩-6-(4-甲基六氩吡畊小基)_i-[4_(2-甲基吡唆-4- 基)苯基胺基羰基】-1Η_吲哚 使用實施例4之類似方法，自4-(2-曱基吡啶-4-基)苯胺 (D49)和5-溴-2,3-二氫-6·(4-甲基六氫吡哜小基)_1H-吲 11 朵（D15)製備得白色固體標題化合物（48%)。 !H NMR (250MHz, CDC13) δ (ppm) ： 8.52 (d, 1H) ^ 7.83 (s5 1H)，7.64-7.52 (m，4H)，7·38-7·33(πι，2Η) , 7.29 (d，1H)， 6·54 (s，1H)，4·11 (t，2H)，3.19 (t，2H)，3.09 (br s，4H)，2·62 (br s，4H+s，3H)，2.35 (s，3H)。 實施例485- 氯_2,3-二氩-6-(4甲基六氬吼__1-基)-l-【4-(2-甲基吼唆* 4_基)苯基胲基羰基】-1H-弓丨哚 使用實施例4之類似方法，自4-(i-甲基吡啶-4-基)笨胺 (D49)和5-氣_2,3_二氫-6-(4-甲基六氫吡畊-1-基MH-, 97 本紙張尺度適用巾關家轉（CNS ) M規格（21QX297公羡） - '^—- .讀先閱讀背面之注意事項再填 •装· 頁) 訂 509687 A7 -----------------B7 五、發明説明（96 ) :朵（D13)製備得米黃色固體標題化合物（79%)。 NMR (250MHz，CDC13) δ (ppm) : 8.52 (d，1H)，7.82 (s， 1H)，7.62-7.50 (m5 4H)，7.34 (s，1Η)，7·28 (dd，1H)，7· 14 (s，1H) ’ 6.52(s，1H)，4·11 (t，2H)，3.18(t，2H)，3.13-3.04 (m，4H) ’ 2·61 (s，3H)，2.60 (br s，4H)，2.34 (s，3H)。 實施例49 5_氣_2,3-二氩-1_【4-(2,6_二甲基吡务4_基)苯基胺基羰基]_ 6-(4-甲基六氩吼基嗦 使用實施例2之類似方法，自4_(2,6_二曱基吡啶基)笨 基異氰酸酯（D62)和5-氣-2,3-二氫·6-(4-甲基六氫吡畊-1_基)-111_吲哚（013)製備得白色固體標題化合物（55%)。 !HNMR (250MHz, CDC13) δ (ppm) ： 7.82 (s, 1H) ^ 7.60-7.50 (m，4H) ’ 7.16-7.11 (m，3H)，6.63 (s，1H)，4.07 (t，2H)，3.15 (t，2H)，3.09(brs，4H)，2.61 (brs，4H)，2.57(s，6H)，2.35 (s, 3H) 〇 實施例50 5-淡_2,3-二氬_1-[4-(2,6-二甲基吡咬_4-基)苯基胺基羰基卜 6_(4-甲基六氮峨喷-1-基略 經濟部智慧財產局員工消費合作社印製 使用實施例2之類似方法，自4-(2,6-二甲基吡啶-4-基)笨 基異酸酿（D62)和5-漠-2,3-二氧-6-(4-甲基六氫°比啡_ 1-基)-1H-吲哚（D15 )製備得白色固體標題化合物（36% ) 〇 iNMR(250MHz，CDC13) δ (ppm) : 7.83 (s，1H)，7.61-7.51 (m，4H)，7·34 (s，1H)，7.16 (s，2H)，6.54 (s，1H)，4.11 (t， 2H)，3.19 (t，2H)，3.09 (brs，4H)，2.62 (brs^H)，2.58 (s， 98 ^張尺度適用中國國家標準（CNS ) A4規格（210 X297公釐） 509687Yan J 8 6 9 A7 B7 V. Description of the invention (93) Printed carbonyl group of the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs) -6- (4-methylhexahydropyrine-1-yl) -1Η-indole ( D43) and 2-furanboronic acid to prepare the title compound to obtain a light beige powder (64%). NMR (250MHz, d6DMSO) δ (ppm): 8.68 (s, 1H), 7.82 (s, 1Η), 7.73 (d, 1H), 7.76 (s, 4Η), 7.25 (s, 1Η), 6.86 (d, 1Η), 6.61 (dd, 1H), 4.18 (t, 2H), 3.15 (t, 2H), 2.95 (br s, 4H), 2.26 (s, 3H). The 2xCH2 signal is obscured by the DMSO signal. Example 425-Gas-2,3-diazine-6- (4-methylhexaazol-1-yl) _1_ [4- (sphino-2-yl) phenylaminocarbonyl] · 1Η · Indigo is used in a similar way to Note 2, starting from 5-gas-2,3-dihydro small (4-iodophenylaminocarbonyl) -6_ (4-methylhexahydropyridine. Well-1-yl) -1) -Indole (D43) and 2-thiophene boronic acid to prepare the title compound to obtain a cream-colored powder (56%). ! H NMR (250MHz, CDC13) δ (ppm): 7.82 (s5 1H) ^ 7.58 (d, 2H), 7.42 (d, 2H), 7.24 (d, 2H), 7.14 (s, 1H), 7.08 (m , 1H), 6.45 (s, 1H), 4.09 (t, 2H), 3.18 (t, 2H), 3.10 (brs, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 435-Gas-2,3-diazine-6- (4-methylhexaazine-1-yl) -1- [5_ (synth-4-yl) naphthalenylethenyl]- 1EM! Indole was used in a similar manner to Example 20 from 5- (pyridin-4-yl) naphthalen-1-ylacetic acid (D25) and 5-gas-2,3-difluoro-6- (4-methyl Hexazine 11 well_1_yl bowline indole (D13) to prepare the title compound. NMR (250MHz? CDC13) δ (ppm): 8.73 (dd5 2H) ^ 8.07 (s, 1H), 8.01 (d, 1H), 7.79 (dd, 1H), 7..61 (dd, 1H), 7.45-7.41 95 This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) (Please read the precautions on the back before filling in HI Page) Binding and binding 8 6 9 A7 B7 V. Description of the invention (94) (m, 5H), 7.19 (s, 1H), 4.27 (s, 2H), 4.26 (t, 2H), 3 19 (t, 2H), 3.05 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 44 5- Australian_2,3-diaza_6- (4_ A Hexafluoro 1-yl) _1- [5_ (stilbyl) naphthyl small ethylacetinyl] -1Η-indole Using a method similar to that in Example 20, 5- (pyridin-4-yl) naphthalene-1 · yl Acetic acid (D25) and 5- &gt; odor-2,3-diazine-6- (4-methylhexazine 〇 比 〇 井 -1-yl) _111-ordinal indole (D15) Preparation of the title NMR (250MHz, CDC13) δ (ppm): 8.73 (d, 2H), 8.08 (s, 1H), 8.00 (d, 1H), 7.78 (dd, 1H), 7. · 60 (dd, 1H), 7.44-7.41 (m, 5H), 7.37 (s, 1H), 4.26 (s, 2H), 4.25 (t5 2H), 3.18 (t, 2H), 3.03 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 45 5-Gas_2,3-Diargonylmethylhexagonol-4-yl) naphthalene small group Aminocarbonyl 1-6- (4-methylhexahydropyridine-1.yl) -1H-pyridine. Using a similar method to that described in Example 4, from 4- (1-methylhexahydropyridine-4-yl) Naphthalen-1-ylamine (D46) and 5-gas-2,3-diazine-6- (4-methylhexaazine) 11-l-yl) -1H-indole (D13) to prepare the title compound. 4 NMR (250MHz, d6DMSO) δ (ppm): 11.06 (br s, 1H), 10.94 (br s, 1H), 8.82 (s, 1Η), 8.27 (dd, 1H), 7.78 (s, 1H) , 7.63 (m, 2H), 7.54 (d, 1H), 7.42 (d, 1H), 7.33 (s, 1H), 4.30 (t, partially shaded, 2H), 3.74 (m, 1H ), 3.24 (t, 2H), 3.60-2.96 (m, 12H), 2.84 (s, 3H), 2.83 (s, 3H), 2.18 (m, 4H). Example 46 96 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) I ----------- install II (please read the boxing items on the back and fill in 1¾ pages) Order Line-Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 B7 V. Description of the Invention (95) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5-5--2,3-diargon [4_0 4-yl) benzylamino] -6- (4-methylhexagonylpyridinyl) -1Η-indole Using a method similar to that described in Example 4, a 4- (4-methylaminophenyl) group ) -2-Methyl-4 salyl (D47) and 5-chloro-2,3-dihydro-6- (4-methylhexahydro. Bispherin_1-yl) -1H-indole (D13) The title compound (67%) as a light yellow powder. 4 NMR (250MHz, d6DMSO) δ (ppm): 8.61 (s, 1H), 8.30 (s, 1Η), 7.74 (s, 1H), 7.57 (dd5 4H), 7.21 (s, 1H), 4.13 (t, 2H), 3.08 (m, 6H), 2.57 (s, 3H), 2.38 (s, 3H). 2xCIMil is obscured by H20 signal. Example 475-bromo_2,3 · diargon-6- (4-methylhexahydropyridine) -i- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl]- 1Η-indole Using a similar method as in Example 4, starting from 4- (2-fluorenylpyridin-4-yl) aniline (D49) and 5-bromo-2,3-dihydro-6 · (4-methylhexa Hydropyridoxine) -1H-Indo (D15) yielded the title compound (48%) as a white solid. ! H NMR (250MHz, CDC13) δ (ppm): 8.52 (d, 1H) ^ 7.83 (s5 1H), 7.64-7.52 (m, 4H), 7.38-7 · 33 (π, 2Η), 7.29 ( d, 1H), 6.54 (s, 1H), 4.11 (t, 2H), 3.19 (t, 2H), 3.09 (br s, 4H), 2.62 (br s, 4H + s, 3H ), 2.35 (s, 3H). Example 485- Chloro_2,3-diargon-6- (4-methylhexaargin-1-yl) -l- [4- (2-methylsulfanyl * 4-yl) phenylfluorenylcarbonyl ] -1H-Arbdodol using a similar method as in Example 4, starting from 4- (i-methylpyridin-4-yl) benzylamine (D49) and 5-gas-2,3_dihydro-6- (4 -Methylhexahydropyridine-1-yl MH-, 97 This paper is suitable for paper towels (CNS) M size (21QX297 public envy)-'^ —-. Please read the precautions on the back before filling · Page) Order 509687 A7 ----------------- B7 V. Description of the invention (96): The title compound (79%) was prepared as a beige solid (D13). NMR (250MHz, CDC13) δ (ppm): 8.52 (d, 1H), 7.82 (s, 1H), 7.62-7.50 (m5 4H), 7.34 (s, 1Η), 7.28 (dd, 1H), 7 14 (s, 1H) '6.52 (s, 1H), 4.11 (t, 2H), 3.18 (t, 2H), 3.13-3.04 (m, 4H)' 2.61 (s, 3H), 2.60 (br s, 4H), 2.34 (s, 3H). Example 49 5_Ga_2,3-Diargon-1_ [4- (2,6-Dimethylpyridin 4-yl) phenylaminocarbonyl] _ 6- (4-methylhexaarginyl嗦 Using a similar method as in Example 2, from 4- (2,6-dipyridylpyridyl) benzyl isocyanate (D62) and 5-Ga-2,3-dihydro · 6- (4-methylhexahydropyridine) (Chen-1_yl) -111_indole (013) prepared the title compound (55%) as a white solid.! HNMR (250MHz, CDC13) δ (ppm): 7.82 (s, 1H) ^ 7.60-7.50 (m, 4H) '7.16-7.11 (m, 3H), 6.63 (s, 1H), 4.07 (t, 2H), 3.15 (t, 2H), 3.09 (brs, 4H), 2.61 (brs, 4H), 2.57 (s , 6H), 2.35 (s, 3H) 〇 Example 50 5-Tan_2,3-diargon_1- [4- (2,6-dimethylpyridin-4-yl) phenylaminocarbonyl Bu 6_ (4-methylhexaazaepent-1-yl, printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, using a similar method as in Example 2, from 4- (2,6-dimethylpyridin-4-yl ) Styryl isoacid (D62) and 5-mo-2,3-dioxo-6- (4-methylhexahydro ° biffin-1-yl) -1H-indole (D15) were prepared as a white solid Title compound (36%) NMR (250 MHz, CDC13) δ (ppm): 7.83 (s, 1H), 7.61-7.51 (m, 4H), 7.34 (s, 1H), 7.16 (s, 2H) , 6.54 (s, 1H), 4.11 (t, 2H), 3.19 (t, 2H), 3.09 (brs, 4H), 2.62 (brs ^ H), 2.58 (s, 98) ) A4 size (210 X297 mm) 509687

6H)，2·35 (s，3H)。 實施例51 2,3_二氬_1_[4_(2,6-二甲基吼咬冬基)苯基胺基羰基】_ 氣基-6-(4_甲基六氬吼基)-111_喷嗔 使用實施例2之類似方法，自4-(2,6-二甲基吡咬_4_基)笨 基異氰酸酯（D62)和2,3-二氫_5_甲氧基_6_(4_甲基六1〇比 畊小基)-1Η-ρ引哚（WO95/06627中間物3)製備得米黃色 固體標題化合物（28%)。 ^ !HNMR(250MHz,CDC13)δ (ppm) ： 7.7〇(S51H) , 7.61.7 5〇 (m，4H)，7·16 (s，2H)，6·74 (s，1H)，6.51 (s，1H)，4·ιι (t， 2H) ’ 3·84 (s，3H) ’ 3·20 (t，2H) ’ 3·13 (br s，4H)，2·62 (br s 4H)，2.58 (s，6H)，2·35 (s，3H)。 ’ 實施例52 5- 氣-2,3-二氩-1-[4-(2,6-二甲基吡唆_3_基)苯基胺基叛基】_ 6- (4-甲基六氩吡1#-1_基)_111-弓丨嗓 使用實施例2之類似方法，自4-(2,6-二曱基吡啶-3-基)苯 基異氰酸酯（D63)和5-氣-2,3-二氫«4·甲基六氫吡畊-1-基)-1Η-吲哚（D13)製備得白色固體標題化合物（21%)。 經濟部智慧財產局員工消費合作社印製 NMR (250MHz，CDC13) δ (ppm) : 7·83 (s，1H)，7.48 (d， 2H)，7·40 (d，1Η)，7·28 (d，2H)，7·16 (s，1H)，7·04 (d，1H)， 6.49 (s，1H)，4·11 (t，2H)，3.20 (t，2H)，3·10 (br s，4H)，2·60 (br s，4H)，2·57 (s，3H)，2.49 (s，3H)，2·35 (s，3H)。 實施例53 S-溴-2,3-二氩_l-[4-(2,6-二甲基吡唆_3-基)苯基胺基羰基】_ 99 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 509687 A7 B7 五、發明説明（98 ) 經濟部智慧財產局員工消費合作社印製 甲基六氩吼牛1-基丨鳴 使用實施例2之類似方法，自4_(2，卜二甲基吡啶_3_基)笨 基異氰酸酯（D63)和5-溴_2,3_二氫-6-(4-甲基六氫吡畊_ 1-基)-1H-吲哚（D15)製備得白色固體標題化合物（44%)。 H NMR (250MHz，CDC13) δ (ppm) : 7.84 (s5 1H)，7.50 (d， 2H) ’ 7·41 (d，1H) ’ 7.35 (s，1H)，7.29 (d，2H)，7.06 (d，1H)， 6.48 (s, 1H) ^ 4.12 (t, 2H) &gt; 3.21 (t3 2H) ^ 3.09(brs54H) ^ 2.60 (bi* s，4H)，2.57 (s，3H)，2.49 (s，3H)，2·35 (s，3H)。 實施例542,3-二氩-1-【4_(2,6-二甲基吡啶各基)苯基胺基羰基】_s甲 氧基-6-(4-甲基六氩吡畊吲哚 使用實施例2之類似方法，自4-(2,6-二甲基吡唆_3-基)苯 基異氰酸酯（D63 )和2,3-二氫-5-甲氧基各(4_甲基六氯吼 畊-1_基)-111·吲哚（WO95/06627中間物3)製備得米黃色 固體標題化合物（17%)。 ' $4 NMR (250MHz，CDC13) δ (ppm) : 7.72 (s，1Η)，7·48 (d 2H)，7·39 (d，1H)，7.25 (d，2H)，7·03 (d，1H)，6·73 (s，ih)， 6.54 (s，1H)，4.09 (t，2H)，3.83 (s，3H)，3·18 (t，2H)，3.12 (brs，4H)，2.6〇(brs，4H)，2.56 (s，3H)，2.48 (s，3H)，2.34 (s，3H)。 實施例555-氣_2,3_二氩-6-(4-甲基六氩吼讲小基)-i_【4_(s_甲基_ 1，2,4_今二唑_3_基)苯基胺基羰基HH-吲哚 使用實施例4之類似方式，自4-(5-甲基-1，2,4巧二唾_3_ 100 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）. (請先閱讀背面之注意事項再填頁) 裝.6H), 2.35 (s, 3H). Example 51 2,3_Diargon_1_ [4_ (2,6-Dimethylpyridinyl) phenylaminocarbonyl] _amino-6- (4-methylhexaarginyl) -111 _ Spraying using a similar method of Example 2, from 4- (2,6-dimethylpyridine_4_yl) benzyl isocyanate (D62) and 2,3-dihydro_5_methoxy_6_ (4-MethylhexalObioxyl) -1H-p-indole (WO95 / 06627 intermediate 3) The title compound (28%) was obtained as a beige solid. ^! HNMR (250MHz, CDC13) δ (ppm): 7.7 (S51H), 7.61.7 50 (m, 4H), 7.16 (s, 2H), 6.74 (s, 1H), 6.51 ( s, 1H), 4.0m (t, 2H) '3.84 (s, 3H)' 3.20 (t, 2H) '3.13 (br s, 4H), 2.62 (br s 4H) , 2.58 (s, 6H), 2.35 (s, 3H). '' Example 52 5-Ga-2,3-Diargon-1- [4- (2,6-dimethylpyridinium_3-yl) phenylaminoalkyl] -6- (4-methyl Hexapyridine 1 # -1_yl) _111-bow Using a method similar to that in Example 2, from 4- (2,6-diamidinopyridin-3-yl) phenyl isocyanate (D63) and 5-amino -2,3-dihydro «4 · methylhexahydropyridin-1-yl) -1Η-indole (D13) to prepare the title compound (21%) as a white solid. NMR (250MHz, CDC13) δ (ppm) printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs: 7.83 (s, 1H), 7.48 (d, 2H), 7.40 (d, 1Η), 7.28 ( d, 2H), 7.16 (s, 1H), 7.04 (d, 1H), 6.49 (s, 1H), 4.11 (t, 2H), 3.20 (t, 2H), 3.10 ( br s, 4H), 2.60 (br s, 4H), 2.57 (s, 3H), 2.49 (s, 3H), 2.35 (s, 3H). Example 53 S-bromo-2,3-diargon-l- [4- (2,6-dimethylpyridinium_3-yl) phenylaminocarbonyl group] _ 99 This paper size applies to Chinese national standards ( CNS) A4 specification (210X297 mm) 509687 A7 B7 V. Description of invention (98) Methyl argon roaring cow 1-based printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs uses a similar method as in Example 2 (2,2-Dimethylpyridin-3-yl) benzyl isocyanate (D63) and 5-bromo_2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1H- Indole (D15) prepared the title compound (44%) as a white solid. H NMR (250MHz, CDC13) δ (ppm): 7.84 (s5 1H), 7.50 (d, 2H) '7.41 (d, 1H)' 7.35 (s, 1H), 7.29 (d, 2H), 7.06 ( d, 1H), 6.48 (s, 1H) ^ 4.12 (t, 2H) &gt; 3.21 (t3 2H) ^ 3.09 (brs54H) ^ 2.60 (bi * s, 4H), 2.57 (s, 3H), 2.49 (s , 3H), 2.35 (s, 3H). Example 542,3-Diargin-1- [4- (2,6-dimethylpyridyl) phenylaminocarbonyl] _smethoxy-6- (4-methylhexapyridineindole use In a similar manner as in Example 2, from 4- (2,6-dimethylpyridin-3-yl) phenyl isocyanate (D63) and 2,3-dihydro-5-methoxy each (4-methyl Hexachloro-1- (1-yl) -111 · indole (WO95 / 06627 intermediate 3) prepared the title compound as a beige solid (17%). '$ 4 NMR (250MHz, CDC13) δ (ppm): 7.72 (s , 1Η), 7.48 (d 2H), 7.39 (d, 1H), 7.25 (d, 2H), 7.03 (d, 1H), 6.73 (s, ih), 6.54 (s, 1H), 4.09 (t, 2H), 3.83 (s, 3H), 3.18 (t, 2H), 3.12 (brs, 4H), 2.60 (brs, 4H), 2.56 (s, 3H), 2.48 ( s, 3H), 2.34 (s, 3H). Example 555-Gas_2,3_diargon-6- (4-methylhexaarginyl) -i_ [4_ (s_methyl_ 1 , 2,4-Dioxazol-3-yl) phenylaminocarbonylHH-indole Using a similar manner as in Example 4, starting from 4- (5-methyl-1,2,4,4-bisalanyl_3_100 This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm). (Please read the precautions on the back before filling in the page).

、1T 線 1 8 6 09 5 A7 B7 五、發明説明（99 經濟部智慧財產局員工消費合作社印製 基)苯胺（德國公開DE 2046928)和5秦2,3_二氣.6| 甲基六氫口比+ 1-基MH令朵（DI3)製備標題化合物。單 離得淡奶油色粉末產物（44%)。 !Η NMR (250MHz，CDC13) δ (ppm) : 8.04 (d，2H)，7·81 (s， 1Η)，7·58 (d，2Η)，7·15 (s，1Η)，6·53 (s，1Η) , 4·10 (t，2Η)，’ 3·19 (t，2H) ’ 3·10 (br s，4H)，2.65 (br s5 4H)，2·60 (br s，4H)， 2·35 (s，3H)。 實施例56 S-氣_2,3-二氩_1-[4-(3_甲基-1，2,4-噚二唑各基)苯基胺基羰 基I_6_(4-甲基六氩吼呼小基鳴 使用實施例4之類似方式，自4-(3-甲基-1，2,4-喝二唑-5-基)苯胺（雜環化學期刊1980，17(6)，1273-5)和5-氣-2,3-二氫-6-(4_甲基六氫吡畊-μ基)-iH_吲哚（D13)製備標題 化合物。単離得淡奶油色粉末產物（0.13克，48%)。 NMR (250MHz，d6DMSO) δ (ppm).: 8·81 (s，1H)，7.84 (d， 2H)，7·71 (d，2H)，7.63 (s，1Η)，4·02 (t，2H)，2·96 (t，2H)， 2·76 (br s，4H)，2·34 (br s，4H)，2·07 (s, 3H)，1·93 (s，3H)。 未觀察到NH質子。 實施例57 5-氣-2,3-二氩-6_(4_甲基六氩吡矫-i-基)_ι_[3-(喊啶_2_基氧 基)苯基胺基羰基ΗΗ-吲哚 使用實施例4之類似方式，自3-(嘧啶-2-基氧基）苯胺 (D71)和5-氯-2,3_二氫_6-(4-曱基六氫吡畊-1-基)-1Η-吲 哚（D13)製備標題化合物。單離得淡米色粉末產物 101 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閲讀背面之注意事項再 裝— 填 訂 線· 509687 A7 B7 五、發明説明（1(X)) (32%)。 NMR (250MHz，d6DMSO) δ (ppm) : 8.55 (m，3H)，7.63 (s，1H)，7·35 (m，2H)，7.26J.10 (m，3H)，6.75 (d，1H)，4.02 (t，2H)，2·99 (t，2H)，2.78 (br s，4H)，2·39 (br s，4H)，2·10 (s5 3H) 〇 實施例58 5-氣-2,3-二氩-6-(4_甲基六氩咕喷-1_基甲基_n_ (嘧啶_2-基)胺基]苯基胺基羰基}-1Η-吲哚 使用實施例4之類似方式’自4-|^-甲基_]^-(喷σ定-2-基)胺 基]苯胺（D73)和5_氯_2,3_二氫_6-(4-甲基六氫。比ϋ井小 基ΜΗ-吲哚（D13)製備標題化合物。單離得淡奶油色粉 末產物（54%)。 i NMR (250MHz，CDC13) δ (ppm) ·· 8·34 (d，2Η)，7·80 (s， 1Η)，7·46 (d，2Η)，7·29 (d，2Η)，7·15 (s，1Η)，6.56 (t，1Η)， 6.42 (s，1H)，4·08 (t，2H)，3.50 (s，3H)，3·18 (t，2H)，3.09 (br s，4H)，2.60 (br s，4H)，2.35 (s，3H)。 實施例59 經濟部智慧財產局員工消費合作社印製 5-溴_2,3-二氩-1_[4_(欢喃-2_基)苯基胺基羰基】_6_(4_甲基 六氬吡畊-1-基)-1Η-弓丨哚 使用實施例4之類似方式，自4-(呋喃-2-基)苯胺（合成 1976，1，40)和5_溴-2,3_二氫各(4-甲基六氫吡畊小 基)-1Η-吲哚（D15)製備標題化合物。單離標題化合物得 奶油色粉末（38%)。 lHNMR (250MHz, d6DMSO) δ (ppm) ： 8.60 (s, 1H)» 7.71 (s5 102 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）. 严； 8 6 9ο A7 B7 五、發明説明（1〇1 ) 1H)，7.60 (d，1H)，7·54 (s，4H)，7.32 (s，1H)，6.74 (d，1H)， 4·08 (t，2H)，3.2 (br s，2H)，3.04 (t，2H)，2.97 (br s，4H)， 2.68 (s，3H)。 實施例60 5_氣-2,3-二氮_6_(4-甲基六氮吼讲_1-基)_l_[4-(逢吩_3_基） 苯基胺基羰基ΗΗ_吲哚 使用說明2之類似方式，自5-氯-2,3-二氫小(4-碘苯基胺 基羰基)-6-(4-甲基六氫吡畊小基)-1Η-吲哚（D43)和3-噻吩硼酸製備標題化合物，獲得奶沛色粉末（31%)。 4 NMR (250MHz，CDC13) δ (ppm) ·· 7·83 (s，1H)，7.57 (d， 2H)，7.45 (d，2H)，7.38 (m，3H)，7·15 (s，1Η)，6.42 (s，1H)， 4.10 (t5 2H)，3-18(t，2H)，3.10 (brs，4H)，2.60 (brs，4H)， 2.35 (s，3H)。 實施例61 5-淡-2,3-二氮-6-(4-甲基六氮吼喷_1·基)-1-[4_(咳峻_2_基) 苯基胺基羰基】-1Η-吲哚 使用實施例4之類似方法，自4-(噻唑-2-基)苯胺（D52) 和5- &gt;臭-2,3-二氮-6-(4-甲基六氮比σ井-1-基)-1Η- 0引σ朵 (D15)製備標題化合物（19%)。 i NMR (250MHz，CDC13) δ (ppm) : 7.92 (d，2H)，7.84(d， 2H)，7.52 (d，2H)，7·32 (d，2H)，6.57 (s，1Η)，4·11 (t，2H)， 3.15(t，2H)，3.13 (brs，4H)，2.69 (brs，4H)，2.42 (s，3H)。 實施例62 5_氣-2,3-二氮-6-(4-甲基六氩吼吨-1_基)_l-[4-(咳峻-2-基) 103 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -----------裝-- (請先閱讀背面之注意事項再1m本頁) 訂 線- 經濟部智慧財產局員工消費合作社印製 509687 t A7 B7五、發明説明（1〇2 ) 經濟部智慧財產局員工消費合作社印製 苯基胺基羰基】-1Η-吲嗦 使用類似於D51之方法，自5-氣-2,3-二氫-1-(4-碘苯基胺 基羰基)-6-(4-曱基六氫吡畊-1-基)-1Η-吲哚（D43)和2-溴噻唑製備標題化合物（8%)。 4 NMR (250MHz，CDC13) δ (ppm) : 7.93 (d，2H)，7.83 (d， 2H)，7·58 (d，2H)，7·28 (d，1H)，7·14 (s，1H)，6.57 (s，1H)， 4.10(t，2H)，3.17(t，2H)，3.11(brs，4H)，2.61(brs，4H)， 2.35 (s，3H) 〇 實施例631-【4·(5_乙醢基嘍吩_2_基)苯基胺基羰基】-5-氣-2,3-二氩_6_ (4-甲基六氩吡畊-1-基)-1Η-弓丨哚 使用說明2之類似方式，自5-氯-2,3-二氫小(4-碘苯基胺 基羰基)-6-(4-甲基六氫吡畊-1-基)-1Ή-吲哚（D43)和5-乙醯基噻吩-2-基硼酸製備標題化合物，獲得稻草色固體 (42%) 〇 !H NMR (250MHz, d6DMSO) δ (ppm) ： 8.77 (s51H) ^ 7.91 (d? 1H)，7.83 (s，1H)，7.70 (m，3H)，7·55 (d，1H)，7·22 (s，1H)， 4.16 (t，2H)，3·18 (t，2H)，2.92 (br s，4H)，2.51 (m，7H)， 2.23 (s，3H)。未觀察到尿素NH。 實施例64 l-(5-澳茶-1-基己斑基)-5-氣-2,3-二氮-6-(4-甲基六氮峨讲-1-基)_1H-吲哚 使用實施例20之類似方法，自5-溴萘-1-基乙酸（法國化 學學會通報1968，7，2957)和5-氣-2,3-二氫-6-(4-甲基 104 (請先閱讀背面之注意事項再· .裝- 頁), 1T line 1 8 6 09 5 A7 B7 V. Description of invention (99 printed by the Consumer Property Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs) aniline (German Publication DE 2046928) and 5 Qin 2,3_ Digas. 6 | Methylhexa Hydrogen ratio + 1-based MH Linguo (DI3) to prepare the title compound. The light cream-colored powder product (44%) was isolated. ! Η NMR (250MHz, CDC13) δ (ppm): 8.04 (d, 2H), 7.81 (s, 1Η), 7.58 (d, 2Η), 7.15 (s, 1Η), 6.53 (s, 1Η), 4.10 (t, 2Η), '3.19 (t, 2H)' 3.10 (br s, 4H), 2.65 (br s5 4H), 2.60 (br s, 4H ), 2.35 (s, 3H). Example 56 S-gas_2,3-diargon_1- [4- (3-methyl-1,2,4-fluoradiazolyl) phenylaminocarbonyl I-6- (4-methylhexaargon Roaring Xiaojiming used a similar method to Example 4 from 4- (3-methyl-1,2,4-diazol-5-yl) aniline (Journal of Heterocyclic Chemistry 1980, 17 (6), 1273 -5) and 5-Gas-2,3-dihydro-6- (4-methylhexahydropyridine- [mu] yl) -iH_indole (D13) to prepare the title compound. A light cream-colored powdery product was obtained by deionization. (0.13 g, 48%). NMR (250 MHz, d6DMSO) δ (ppm) .: 8.81 (s, 1H), 7.84 (d, 2H), 7.71 (d, 2H), 7.63 (s, 1Η) ), 4.02 (t, 2H), 2.96 (t, 2H), 2.76 (br s, 4H), 2.34 (br s, 4H), 2.07 (s, 3H), 1 · 93 (s, 3H). No NH protons were observed. Example 57 5-Gas-2,3-diargon-6_ (4-methylhexapyridine-i-yl) _ι_ [3- (yridine _2_yloxy) phenylaminocarbonylfluorene-indole In a similar manner to Example 4, starting from 3- (pyrimidin-2-yloxy) aniline (D71) and 5-chloro-2,3_di Hydrogen-6- (4-fluorenylhexahydropyrine-1-yl) -1fluorene-indole (D13). The title compound was prepared. The product was isolated as a light beige powder. 101 This paper is in accordance with China National Standard (CNS) A4 specifications. 210X297 mm) (Please read the precautions on the back before loading—filling line · 509687 A7 B7 V. Description of the invention (1 (X)) (32%). NMR (250MHz, d6DMSO) δ (ppm): 8.55 ( m, 3H), 7.63 (s, 1H), 7.35 (m, 2H), 7.26J.10 (m, 3H), 6.75 (d, 1H), 4.02 (t, 2H), 2.99 (t , 2H), 2.78 (br s, 4H), 2.39 (br s, 4H), 2.10 (s5 3H). Example 58 5-Gas-2,3-Diargon-6- (4_A Hexyl-1,1-methyl-n- (pyrimidin-2-yl) amino] phenylaminocarbonyl} -1'-indole Using a similar manner as in Example 4, 'from 4- | ^ -methyl _] ^-(Spray stilb-2-yl) amino] aniline (D73) and 5-chloro_2,3_dihydro-6- (4-methylhexahydro. Than the well small group MΗ-ind Indole (D13) prepared the title compound. Isolation yielded a light cream-colored powder product (54%). I NMR (250MHz, CDC13) δ (ppm) ····················································· ), 7.46 (d, 2Η), 7.29 (d, 2Η), 7.15 (s, 1Η), 6.56 (t, 1Η), 6.42 (s, 1H), 4.08 (t, 2H ), 3.50 (s, 3H), 3.18 (t, 2H), 3.09 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 59 Printing of 5-bromo_2,3-diargon-1_ [4_ (huanan-2_yl) phenylaminocarbonyl]] _ 6_ (4_methylhexaargylpyridine) Ghen-1-yl) -1H-toxin Indole was used in a similar manner to Example 4, starting from 4- (furan-2-yl) aniline (synthesis 1976, 1,40) and 5-bromo-2,3_dihydro (4-methylhexahydropyridyl) -1H-indole (D15) each to prepare the title compound. Isolation of the title compound gave a cream-colored powder (38%). lHNMR (250MHz, d6DMSO) δ (ppm): 8.60 (s, 1H) »7.71 (s5 102) This paper size is applicable to China National Standard (CNS) A4 (210X297 mm). Strict; 8 6 9ο A7 B7 V. Invention Explanation (10.1) 1H), 7.60 (d, 1H), 7.54 (s, 4H), 7.32 (s, 1H), 6.74 (d, 1H), 4.08 (t, 2H), 3.2 ( br s, 2H), 3.04 (t, 2H), 2.97 (br s, 4H), 2.68 (s, 3H). Example 60 5-Gas-2,3-diaza-6_ (4-methylhexazine-1-yl) _l_ [4- (perphen-3-yl) phenylaminocarbonylfluorene_indole In a similar way as described in Instruction 2, starting from 5-chloro-2,3-dihydro small (4-iodophenylaminocarbonyl) -6- (4-methylhexahydropyridine) -1Η-indole ( D43) and 3-thiophene boronic acid to prepare the title compound to obtain a creamy powder (31%). 4 NMR (250MHz, CDC13) δ (ppm) ·· 83 (s, 1H), 7.57 (d, 2H), 7.45 (d, 2H), 7.38 (m, 3H), 7.15 (s, 1Η ), 6.42 (s, 1H), 4.10 (t5 2H), 3-18 (t, 2H), 3.10 (brs, 4H), 2.60 (brs, 4H), 2.35 (s, 3H). Example 61 5-Ethane-2,3-diazine-6- (4-methylhexazine-1-yl) -1- [4- (kejun_2_yl) phenylaminocarbonyl]- 1Η-indole Using a similar method as in Example 4, from 4- (thiazol-2-yl) aniline (D52) and 5- &gt; odor-2,3-diaza-6- (4-methylhexazine ratio σ well-1-yl) -1Η-0 was used to prepare the title compound (19%). i NMR (250MHz, CDC13) δ (ppm): 7.92 (d, 2H), 7.84 (d, 2H), 7.52 (d, 2H), 7.32 (d, 2H), 6.57 (s, 1Η), 4 -11 (t, 2H), 3.15 (t, 2H), 3.13 (brs, 4H), 2.69 (brs, 4H), 2.42 (s, 3H). Example 62 5_Gas-2,3-diazine-6- (4-methylhexahydroxan-1-yl) _l- [4- (kejun-2-yl) 103 This paper is applicable to China Standard (CNS) A4 specification (210X297 mm) ----------- install-(Please read the precautions on the back before 1m page) Threading-Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and the Consumer Consumption Cooperative 509687 t A7 B7 V. Description of the invention (102) Phenylaminocarbonyl group printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs] -1Η-Indine using a method similar to D51, from 5-Gas-2,3 -Dihydro-1- (4-iodophenylaminocarbonyl) -6- (4-fluorenylhexahydropyridin-1-yl) -1fluorene-indole (D43) and 2-bromothiazole to prepare the title compound ( 8%). 4 NMR (250MHz, CDC13) δ (ppm): 7.93 (d, 2H), 7.83 (d, 2H), 7.58 (d, 2H), 7.28 (d, 1H), 7.14 (s, 1H), 6.57 (s, 1H), 4.10 (t, 2H), 3.17 (t, 2H), 3.11 (brs, 4H), 2.61 (brs, 4H), 2.35 (s, 3H). Example 631- [ 4 · (5-Ethylfluoren-2-yl) phenylaminocarbonyl group] -5-Ga-2,3-diargon-6_ (4-methylhexaargin-1-yl) -1Η -Indole is used in a similar manner to Instruction 2 from 5-chloro-2,3-dihydro small (4-iodophenylaminocarbonyl) -6- (4-methylhexahydropyridine-1-yl) -1Ή-Indole (D43) and 5-Ethylthiophene-2-ylboronic acid to prepare the title compound to obtain a straw-colored solid (42%).! H NMR (250MHz, d6DMSO) δ (ppm): 8.77 (s51H) ^ 7.91 (d? 1H), 7.83 (s, 1H), 7.70 (m, 3H), 7.55 (d, 1H), 7.22 (s, 1H), 4.16 (t, 2H), 3.18 (t, 2H), 2.92 (br s, 4H), 2.51 (m, 7H), 2.23 (s, 3H). No urea NH was observed. Example 64 l- (5-Aucha-1-ylhexanyl) -5-qi-2,3-diazine-6- (4-methylhexaazol-1-yl) _1H-indole Using a similar method to Example 20, 5-bromonaphthalene-1-ylacetic acid (French Chemical Society Bulletin 1968, 7, 2957) and 5-Gas-2,3-dihydro-6- (4-methyl 104 ( (Please read the precautions on the back before loading ...-page)

、1T 線 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 509687 A7 ________^B7五、發明説明（1〇3 ) 經濟部智慧財產局員工消費合作社印製 六氫吡畊-1-基)-1Η-吲哚（Dl3)製備得淡黃色泡沫標 合物（62%)。 τ b 4 NMR (250MHz，CDC13) δ (ppm) : 8·26 (d，1H)，7 s 1H)，7·83 (d，1H)，7.65 (t，1H)，7·45 (d，1H)，7.37 (t S， 7·15 (s，1H)，4.22 (s，2H)，4·19 (t，2H) , 3.15 (t，2¾，2 95 (br s，4H)，2.48 (br s，4H)，2.17 (s，3H)。 實施例65 5_氣_2,3-二氩-6_(4_甲基六氣吡+i基)el普笨基喳唯4 基胺基羰基)_1Η·吲哚 ~ _ 使用實施例4之類似方法，自5_胺基-8_苯基喳啩（D66) 和5-氯-2,3-二氫-6-(4-甲基六氫吡畊-μ基)巧丨鳴 (D13)製備得奶油色固體標題化合物（4〇〇/0)。 水 4 NMR (250MHz，CDC13) δ (ppm) : 8.95 (dd，1Η)，&amp;29 ⑽ 1H)，7·83 (s，1H)，7.72-7.65 (m，3H)，7.53-7.38 (m，5H)，’ 7·18 (s，1H)，6·67 (s，1H)，4.22 (t，2H)，3.24 (t，2H)，3 〇6 (br s，4H)，2.56 (br s，4H)，2.32 (s，3H)。 實施例66 5-澳_2,3_二氩-6-(4-甲基六氩吡喷小基)_i普笨基咬琳$ 基胺基羰基)_1H嚿丨哚 _ _ 使用實施例4之類似方法，自5_胺基_8_苯基喳唯（D66) 和5-溴_2,3_二氫-6_(4-甲基六氫·吼畊-1-基吲哚 (D15)製備得奶油色固體標題化合物（25%)。 !H NMR (250MHz, CDC13) δ (ppm) ： 8.96 (dd, 1H) ^ 8.31 (dd, 1H) ’ 7.84 (s，1H) ’ 7.74-7.66 (m，4H)，7·52-7·41 (m，4H) ’ 105 本紙張尺度適用中國國家榡準（CNS )八4祕（210X297公釐） 一 ~^ (請先閲讀背面之注意事項再^1|本頁} .裝· -訂- 線- 509687 A7 B7 五、發明説明（1〇4 ) 經濟部智慧財產局員工消費合作社印製 7.38 (s，1H)，6.65 (s，1H)，4·25 (t，2H)，3.27 (t，2H)，3.05 (br s，4H)，2·57 (br s，4H)，2.32 (s，3H)。實施例675-氣-2,3-二氩_6-(4-甲基六氩吡畊_i_基)_l-[2-(2-苯基乙基) 喳啉冬基胺基羰基】-1Ηβ丨哚 使用實施例4之類似方法，自6-胺基-2-(2-苯基乙基)喳咐 (D69)和5-氯-2,3-二氫_6_(4_甲基六氫吡畊小基)_ιη-, 哚（D13)製備得白色固體標題化合物（77%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.09 (d，1Η)，8.01 (d， 1H)，7·99 (d，1H)，7·85 (s，1H)，7·56 (dd，1H)，7·31_7·15 (m5 7H)，6.62 (s，1H)，4.12 (t，2H)，3.30-3.11 (m510H)，2.61 (br s，4H)，2·35 (s，3H)。實施例68氣_2,3_二氮-6-(4-甲基六氩吼喷-1-基)-l-[5-(l甲基六氣 吡畊-4_基)萘-1-基胺基羰基ΗΗβ丨哚 使用實施例4之類似方法，自5-(1-甲基六氫吡畊-4-基)萘 -1-基胺基（D77)和5-氣-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D13)製備得白色固體標題化合物（15%)。 lR NMR (250MHz, CDC13) δ (ppm) ： 7.99 (d? 1H) ^ 7.79 (m5 3H)，7·50 (m，3H)，7.16 (s，1H)，6.70 (s，1H)，4.24 (t，2H)， 3.32 (m，1H)，3·24 (t，2H)，3.04 (br s，4H)，2.56 (br s，6H)， 2.38 (s，3H)，2.32 (s，3H)，2.21(m，2H)，1.97 (m，4H)。實施例695-溴-2,3_二氩_1_【4-(異喳啉_4_基)苯基胺基羰基】_6_(4-甲 106 (請先閲讀背面之注意事項再HP本頁} 裝· 本紙張尺度適用中國國家榡準（CNS ) A4規格（210X297公釐）1. The paper size of the 1T line is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 509687 A7 ________ ^ B7 V. Description of the invention (103) Hexahydropyridine printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs -1-yl) -1fluorene-indole (Dl3) was prepared as a pale yellow foam standard compound (62%). τ b 4 NMR (250MHz, CDC13) δ (ppm): 8.26 (d, 1H), 7 s 1H), 7.83 (d, 1H), 7.65 (t, 1H), 7.45 (d, 1H), 7.37 (t S, 7.15 (s, 1H), 4.22 (s, 2H), 4.19 (t, 2H), 3.15 (t, 2¾, 2 95 (br s, 4H), 2.48 ( br s, 4H), 2.17 (s, 3H). Example 65 5_Ga_2,3-Diargon-6_ (4-Methylhexapyridine + i-yl) elbenzylsulfonyl-4-ylamino Carbonyl) _1Η · indole ~ _ Using a similar method to that described in Example 4, from 5-amino-8-phenylphosphonium (D66) and 5-chloro-2,3-dihydro-6- (4-methyl Hexahydropyridine-μ-based) (D13) prepared the title compound (400/0) as a cream-colored solid. Water 4 NMR (250MHz, CDC13) δ (ppm): 8.95 (dd, 1Η), &amp; 29 ⑽ 1H), 7.83 (s, 1H), 7.72-7.65 (m, 3H), 7.53-7.38 (m, 5H), '7 · 18 (s, 1H), 6.67 (s, 1H ), 4.22 (t, 2H), 3.24 (t, 2H), 3.0 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 66 5-Au_2,3_diargon-6- (4-methylhexaarginylpyridinyl) _i-benzylphenylaminocarbonyl) _1H 嚿 丨 indole_ _ Example 4 A similar method, from 5-amino-8-phenylpyridine (D66) and 5-bromo_2,3_dihydro-6_ (4-methylhexahydro · Hougen-1-ylindole (D15 ) The title compound (25%) was prepared as a cream-colored solid.! H NMR (250MHz, CDC13) δ (ppm): 8.96 (dd, 1H) ^ 8.31 (dd, 1H) '7.84 (s, 1H)' 7.74-7.66 (m, 4H), 7.52-7 · 41 (m, 4H) '105 This paper size is applicable to China National Standards (CNS) Eighty-fourth Secret (210X297 mm) 1 ~ ^ (Please read the notes on the back first ^ 1 | This page}. Assembling · -Ordering-Line-509687 A7 B7 V. Description of the invention (104) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 7.38 (s, 1H), 6.65 (s, 1H) , 4.25 (t, 2H), 3.27 (t, 2H), 3.05 (br s, 4H), 2.57 (br s, 4H), 2.32 (s, 3H). Example 675- 气 -2, 3-Diargon_6- (4-methylhexapyridine_i_yl) _l- [2- (2-phenylethyl) pyridinolylaminocarbonyl] -1Ηβ 丨 Indole Example 4 A similar method, from 6-amino-2- (2-phenylethyl) to (D69) and 5-chloro-2,3 -Dihydro-6- (4-methylhexahydropyridine) -ιη-, indole (D13) to prepare the title compound (77%) as a white solid. 4 NMR (250MHz, CDC13) δ (ppm): 8.09 (d , 1Η), 8.01 (d, 1H), 7.99 (d, 1H), 7.85 (s, 1H), 7.56 (dd, 1H), 7.31_7 · 15 (m5 7H), 6.62 ( s, 1H), 4.12 (t, 2H), 3.30-3.11 (m510H), 2.61 (br s, 4H), 2.35 (s, 3H). Example 68 gas_2,3_diazine-6- (4-methylhexaargin-1-yl) -l- [5- (lmethylhexafluoropyridin-4-yl) naphthalene-1-ylaminocarbonylcarbonyl β β indole was similar to that used in Example 4 Method from 5- (1-methylhexahydropyridine-4-yl) naphthalen-1-ylamino (D77) and 5-gas-2,3-dihydro-6- (4-methylhexahydro Pycnogenol-1-yl) -1Η-indole (D13) prepared the title compound (15%) as a white solid. LR NMR (250MHz, CDC13) δ (ppm): 7.99 (d? 1H) ^ 7.79 (m5 3H) , 7.50 (m, 3H), 7.16 (s, 1H), 6.70 (s, 1H), 4.24 (t, 2H), 3.32 (m, 1H), 3.24 (t, 2H), 3.04 (br s, 4H), 2.56 (br s, 6H), 2.38 (s, 3H), 2.32 (s, 3H), 2.21 (m, 2H), 1.97 (m, 4H). Example 695-bromo-2,3_diargon_1_ [4- (isofluorin_4_yl) phenylaminocarbonyl] _6_ (4-methyl106 (Please read the precautions on the back before HP page } Packing · This paper size is applicable to China National Standard (CNS) A4 (210X297 mm)

A 509687 A7 B7 五、發明説明（1〇5 ) 基六氬吼_-1-基)_1H-弓1嘴 使用實施例2之類似方法，自4-(異喳啉-4-基)苯基異氰酸 酯（D54)和5-溴-2,3-二氫-6_(4-甲基六氫吡畊-1_基)-出_ 吲哚（D15)製備得白色固體標題化合物（24%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 9.25 (s? 1H) ^ 8.47 (s, 1H)，8.05 (d，1H)，8.01 (d，1H)，7.86 (s，1H)，7.68 (m，2H)， 7.59 (d5 2H)，7.50 (d，2H)，7.36 (s，1H)，6.57(s，1H)，4.16 (t，2H)，3.26 (t，2H)，3.10 (br s，4H)，2.61 (br s5 4H)，2·36 (s5 3H) 〇 實施例70 S-氯·2,3-二氩-l-【4-(異喳啉-4-基)苯基胺基羰基】-6-(4-甲 基六氣吼讲-l-基)-1Η-弓丨蜂 使用實施例2之類似方法，自4-(異4啉-4-基)苯基異氰酸 酯（D54)和5-氯-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D13)製備得白色固體標題化合物（25%)。 4 NMR (250MHz，CDC13) δ (ppm) : 9.25 (s，1H)，8.47 (s， 1H)，8·02 (d，1H)，7.94 (d，1H)，7.85 (s，1Η)，7·76 (m，2H)， 7.61 (d，2H)，7.49 (d，2H)，7.16(s，1H)，6.60 (s，1H)，4.16 (t5 2H)，3·25 (t，2H)，3.18 (br s，4H)，2·61 (br s，4H)，2·35 (s，3H) 〇 實施例71 5-溴_2,3-二氩-6-(4-甲基六氩吡畊-1-基)-l_【4-(喳啉-3_基) 苯基胺基羰基HH-吲哚 使用實施例2之類似方法，自4-(喳啉-3-基)苯基異氰酸酯 107 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） -----------裝^-- (請先閱讀背面之注意事項再本頁) 、1Τ -線- 經濟部智慧財產局員工消費合作社印製 509687 A7 __B7五、發明説明（1〇6 ) 經濟部智慧財產局員工消費合作社印製 (DS6)和5-溴_2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲 :朵（D15)製備得純白色固體標題化合物（6%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 9.17 (s5 1H) ^ 8.27 (d5 1H)，8.13 (d，1H)，7·85 (m，2H)，7·62 (m，6H)，7.34 (s，1H)， 6.57(s，1H) ’ 4.14(t，2H)，3.20(t，2H)，3.17(brs，4H)，2·62 (br s，4H)，2.37 (s，3H)。 實施例725_氣-2,3-二氩-6-(4-甲基六氩吡畊小基)啉-3_基） 苯基胺基獲基】-1H_H嘴 使用實施例2之類似方法，自4-(咹咁-3-基)苯基異氰酸酯 (D56)和5-乳-2,3-二氫-6-(4_甲基六氫σ比σ井-1-基)-1Η-口引 哚（D13)製備得淡米黃色固體標題化合物（1〇%)。 H NMR (250MHz, CDC13) δ (ppm) · 9.17 (s, 1H) J 8.27 (s, 1H)，8.13 (d，1H)，7·87 (d，1H)，7.84 (s，1H)，7·73 (m，3H)， 7.60 (m，3H)，7.16 (s，1H)，6.54(s，1H)，4.14 (t，2H)，3.21 (t，2H)，3.12 (br s，4H)，2·62 (br s5 4H)，2·36 (s，3H)。 實施例735_氣-2,3-—氣甲基六氣啦喷-i-基甲基-1，2,3,4-四氬異喳琳基)胺基羰基HH-吲哚 使用實施例4之類似方法，自7-胺基-2-曱基-1，2,3,4-四氫 異喳咁（D78)和5-氣-2,3-二氫-6-(4-甲基六氫吡畊小 基丨哚（D13)製備得純白色固體標題化合物 (23%) 〇 NMR (250MHz，CDC13) δ (ppm) ·· 7.80 (s，1Η)，7.10 (m， 108 本紙張尺度適用中國國家標準（CNS ) M規格（21〇χΪ97公釐) 一 ~ (請先閱讀背面之注意事項再 裝· 頁) 訂 509687 A7 B7 經濟部智慧財產局員工消費合作社印製 五、發明説明（1σ7) 4H)，6·36 (s5 1H)，4.04 (t，2H)，3.55 (s，2H)，3.15 (t，4H)， 3·09 (br s，4H)，2·87 (m，2H)，2·66 (m，2H)，2.59 (br s，4H)， 2.44 (s，3H)，2·34 (s，3H)。 實施例745·溴-2,3_二氩_6-(4_甲基六氩吡畊-1-基)_l-【2-甲基_1，2,3,4-四氩異喳啉-7-基)胺基羰基】_1H-吲哚 使用實施例4之類似方法，自7-胺基-2-曱基-1，2,3,4-四氫 異喳咁（D78)和5_溴-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D15)製備得純白.色固體標題化合物 (41%)。 4 NMR (250MHz，CDC13) δ (ppm) : 7.80 (s，1Η)，7.32 (s， 1Η)，7·09 (m，3H)，6·35 (s，1H)，4.05 (t，2H)，3·55 (s5 2H)， 3·16 (t，2H)，3.07 (br s，4H)，2·87 (m，2H)，2.67 (m，2H)， 2.59 (br s，4H)，2.44 (s，3H)，2.34 (s，3H)。 實施例755-澳-2,3_二氮-6_(4-甲基六氮峨殊-1-基)_l-[4_(咳琳-8-基) 苯基胺基羰基吲哚 使用實施例2之類似方法’自4-(ϋ奎咐-8-基)苯基異氮酸酯 (D58 )和5_&gt;臭-2,3_二鼠-6-(4-曱基六鼠°比°井-1_基)-1Η-口引 哚（D15)製備得白色固體標題化合物（52%)。 !H NMR (250MHz，CDC13) δ (ppm) : 8.94 (m，1H)，8.20 (m， 1H)，7·84 (s，1Η)，7.82 (d，1H)，7.62 (m，6H)，7.41 (m，1Η)， 7·36 (s，1H)，6.53 (s，1H)，4.12 (t，2H)，3·19 (t，2H)，3.10 (br s，4H)，2.61 (br s，4H)，2.35 (s，3H)。 109 (請先閱讀背面之注意事項再ml本頁) 、1' 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） ^ &gt; 8 6 9 A7 __B7 五、發明説明（1〇8 ) 實施例76 S-氯-2,3-二氩-6-(4-甲基六氩吡畊_1·基)-1-[4-(喳啉-8-基） 苯基胺基羰基HH-吲哚 使用實施例2之類似方法，自4-(喳啉-8-基)苯基異氰酸酯 (D58 )和5-氯-2,3-二氫-6-(4-甲基六氫吡畊小基)-1Η-吲 哚（D13)製備得白色固體標題化合物（71%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 8.93 (m51H) ^ 8.20 (d? 1H)，7·80 (m，2H)，7.57 (m，6H)，7.41 (m，1H)，7.15 (s，1H)， 6.53 (s，1H)，4·12 (t，2H)，3.19 (t，2H)，3.12 (br s，4H)，2.62 (br s，4H)，2.37 (s，3H)。 實施例77 S»氣-2,3_二氩_1_【4_(咪唑_1-基)苯基胺基羰基】冬(4_甲基 六氩吼1#·!·基)_1Η-^5丨鳴 使用實施例4之類似方式，自4-(咪唾基)苯胺（醫藥化 學期刊 1988，31(11)，2136)和 5-氯_2,3_二氫-6-(4-曱基 六氫吼畊小基)-1Η-吲哚（D13)製備標題化合物。單離得 淺奶油色粉末產物（42%)。 !HNMR(250MHz3 d6DMSO) δ (ppm): 8.7〇 (s? 1Η) ^ 8.20 (s? 1H)，7·81 (s，1H)，7.72 (m，3H)，7·57 (d5 2H)，’7.25 (s，1H)，’ 7.12 (s，1H) ’ 4·21 (t，2H)，3.15 (t，2H)，2.94 (m，4H)，2.52 (br s，4H)，2.25 (s，3H)。 實施例78 5-氣-2,3_二氩_6-(4_甲基六氩吼呼4_基)小【4_(吡啶-4-基) 苯基胺基羰基】-ΙΗ-弓丨嗦 110 本紙張尺度適用中國國篆^準（CNS ) A4規格（210X297公着了〜-—- (請先閲讀背面之注意事項再I^本頁) -裝·A 509687 A7 B7 V. Description of the invention (105) Hexahexan-1-yl) _1H-bow 1 Using a method similar to that in Example 2, from 4- (isofluorin-4-yl) phenyl Isocyanate (D54) and 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridine-1-yl) -out-indole (D15) prepared the title compound (24%) as a white solid. lH NMR (250MHz, CDC13) δ (ppm): 9.25 (s? 1H) ^ 8.47 (s, 1H), 8.05 (d, 1H), 8.01 (d, 1H), 7.86 (s, 1H), 7.68 (m , 2H), 7.59 (d5 2H), 7.50 (d, 2H), 7.36 (s, 1H), 6.57 (s, 1H), 4.16 (t, 2H), 3.26 (t, 2H), 3.10 (br s, 4H), 2.61 (br s5 4H), 2.36 (s5 3H) 〇 Example 70 S-chloro · 2,3-diargon-l- [4- (isofluorin-4-yl) phenylamino Carbonyl group] -6- (4-methylhexazine-l-yl) -1Η-bone 丨 Bee was similar to that used in Example 2 from 4- (iso4-line-4-yl) phenyl isocyanate (D54 ) And 5-chloro-2,3-dihydro-6- (4-methylhexahydropyrine-1-yl) -1H-indole (D13) to prepare the title compound (25%) as a white solid. 4 NMR (250MHz, CDC13) δ (ppm): 9.25 (s, 1H), 8.47 (s, 1H), 8.02 (d, 1H), 7.94 (d, 1H), 7.85 (s, 1Η), 7 76 (m, 2H), 7.61 (d, 2H), 7.49 (d, 2H), 7.16 (s, 1H), 6.60 (s, 1H), 4.16 (t5 2H), 3.25 (t, 2H) , 3.18 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H) 〇 Example 71 5-bromo_2,3-diargon-6- (4-methylhexa Argonyl-1-yl) -l- [4- (fluorin-3-yl) phenylaminocarbonyl HH-indole Using a method similar to that in Example 2, from 4- (fluorin-3-yl) benzene Base isocyanate 107 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) ----------- installation ^-(Please read the precautions on the back before this page), 1T -Line- Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 __B7 V. Description of the Invention (1 06) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (DS6) and 5-Bromo_2,3-dihydro- 6- (4-methylhexahydropyridin-1-yl) -1H-indole: Duo (D15) was prepared as the title compound (6%) as a pure white solid. lH NMR (250MHz, CDC13) δ (ppm): 9.17 (s5 1H) ^ 8.27 (d5 1H), 8.13 (d, 1H), 7.85 (m, 2H), 7.62 (m, 6H), 7.34 (s, 1H), 6.57 (s, 1H) '4.14 (t, 2H), 3.20 (t, 2H), 3.17 (brs, 4H), 2.62 (br s, 4H), 2.37 (s, 3H) . Example 725_Gas-2,3-Diargon-6- (4-methylhexaarginyl) Phenyl-3-yl) phenylamino group] -1H_H Mouth uses a similar method as in Example 2 , From 4- (fluoren-3-yl) phenyl isocyanate (D56) and 5-lacto-2,3-dihydro-6- (4-methylhexahydroσσσσ-1-yl) -1Η -Indole (D13) prepared the title compound (10%) as a light beige solid. H NMR (250MHz, CDC13) δ (ppm) · 9.17 (s, 1H) J 8.27 (s, 1H), 8.13 (d, 1H), 7.87 (d, 1H), 7.84 (s, 1H), 7 73 (m, 3H), 7.60 (m, 3H), 7.16 (s, 1H), 6.54 (s, 1H), 4.14 (t, 2H), 3.21 (t, 2H), 3.12 (br s, 4H) , 2.62 (br s5 4H), 2.36 (s, 3H). Example 735_Gas-2,3 --- Gas methylhexapapone-i-ylmethyl-1,2,3,4-tetra-argon isofluorenyl) aminocarbonyl HH-indole Example of use Similar method of 4, from 7-amino-2-fluorenyl-1,2,3,4-tetrahydroisofluorene (D78) and 5-gas-2,3-dihydro-6- (4-methyl Hexahydropyridine small indole (D13) to prepare the title compound as a pure white solid (23%). NMR (250MHz, CDC13) δ (ppm). 7.80 (s, 1Η), 7.10 (m, 108 sheets) Standards are applicable to Chinese National Standards (CNS) M specifications (21〇χΪ97 mm) I ~ (Please read the precautions on the back before re-installing · Page) Order 509687 A7 B7 Printed by the Consumers ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs (1σ7) 4H), 6.36 (s5 1H), 4.04 (t, 2H), 3.55 (s, 2H), 3.15 (t, 4H), 3.09 (br s, 4H), 2.87 (m , 2H), 2.66 (m, 2H), 2.59 (br s, 4H), 2.44 (s, 3H), 2.34 (s, 3H). Example 745 Bromine-2,3_diargon_ 6- (4-methylhexapyridin-1-yl) -1-l- [2-methyl_1,2,3,4-tetraarginoisofluorin-7-yl) aminocarbonyl] _1H-indole Using a similar method to Example 4, from 7-amino-2-fluorenyl-1,2,3,4-tetrahydroisofluorene ( D78) and 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1fluorene-indole (D15) were prepared as a pure white solid. The title compound was a solid (41%). . 4 NMR (250MHz, CDC13) δ (ppm): 7.80 (s, 1Η), 7.32 (s, 1Η), 7.09 (m, 3H), 6.35 (s, 1H), 4.05 (t, 2H) , 3.55 (s5 2H), 3.16 (t, 2H), 3.07 (br s, 4H), 2.87 (m, 2H), 2.67 (m, 2H), 2.59 (br s, 4H), 2.44 (s, 3H), 2.34 (s, 3H). Example 755-A-2,3_diaza-6_ (4-methylhexaazaeshu-1-yl) -1- [4- (kelin-8-yl) phenylaminocarbonylindole Example of use A similar method of 2 'is from 4- (Aquinol-8-yl) phenylisocyanate (D58) and 5_ &gt; Sm-2,3_dirat-6- (4-amidylhexarat °°° Well-1_yl) -1H-portal indole (D15) prepared the title compound (52%) as a white solid. ! H NMR (250MHz, CDC13) δ (ppm): 8.94 (m, 1H), 8.20 (m, 1H), 7.84 (s, 1Η), 7.82 (d, 1H), 7.62 (m, 6H), 7.41 (m, 1Η), 7.36 (s, 1H), 6.53 (s, 1H), 4.12 (t, 2H), 3.19 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H). 109 (Please read the precautions on the back of this page first, then this page), 1 'This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) ^ &gt; 8 6 9 A7 __B7 V. Description of the invention (1〇 8) Example 76 S-Chloro-2,3-diargon-6- (4-methylhexapyridin-1-yl) -1- [4- (fluorin-8-yl) phenylamino The carbonyl HH-indole was similar to that used in Example 2 from 4- (fluorin-8-yl) phenyl isocyanate (D58) and 5-chloro-2,3-dihydro-6- (4-methylhexa Hydropyridine) -1H-indole (D13) yielded the title compound (71%) as a white solid. lH NMR (250MHz, CDC13) δ (ppm): 8.93 (m51H) ^ 8.20 (d? 1H), 7.80 (m, 2H), 7.57 (m, 6H), 7.41 (m, 1H), 7.15 (s , 1H), 6.53 (s, 1H), 4.12 (t, 2H), 3.19 (t, 2H), 3.12 (br s, 4H), 2.62 (br s, 4H), 2.37 (s, 3H). Example 77 S »Gas-2,3_diargon_1_ [4_ (imidazole_1-yl) phenylaminocarbonyl] dong (4_methylhexaargin 1 # ·! · Yl) _1Η- ^ 5丨 Ming used a similar manner as in Example 4 from 4- (imidosyl) aniline (Journal of Medicinal Chemistry 1988, 31 (11), 2136) and 5-chloro_2,3_dihydro-6- (4- 曱Hexahydroquinone) -l-indole (D13) to prepare the title compound. Isolation yielded a light cream powder product (42%). ! HNMR (250MHz3 d6DMSO) δ (ppm): 8.7 (s? 1Η) ^ 8.20 (s? 1H), 7.81 (s, 1H), 7.72 (m, 3H), 7.57 (d5 2H), '7.25 (s, 1H),' 7.12 (s, 1H) '4.21 (t, 2H), 3.15 (t, 2H), 2.94 (m, 4H), 2.52 (br s, 4H), 2.25 (s , 3H). Example 78 5-Gas-2,3_diargon-6- (4-methylhexaarginol 4-yl) small [4_ (pyridin-4-yl) phenylaminocarbonyl] -lΗ-bow 丨嗦 110 This paper size is applicable to China's national standard (CNS) A4 size (210X297 was published ~ ---- (Please read the precautions on the back before I ^ this page)-Packing ·

、1T 經濟部智慧財產局員工消費合作社印製 509687 A7 B7五、發明説明（1〇9) 經濟部智慧財產局員工消費合作社印製 使用說明2之類似方式，自5-氣-2,3-二氫小[4-碘苯基胺 基羰基]-6-(4-甲基六氫吡4-1-基)-1H-吲哚（D43)和4-吡啶硼酸（醫藥化學期刊1997，40(22)，3542)製備標題 化合物。單離得淺黃色固體產物（46%)。 lH NMR (250MHz，d6DMSO) δ (ppm): 8·51 (s，1H)，8.36 (d， 2H)，7.57-7.42 (m，7H)，7.00 (s，1H)，3·92 (t，2H)，2.94 (t5 2H)，2.71 (m5 4H)，2.02 (s，3H)。4H 受到 DMSO 訊號遮 蔽。 .實施例792,3·二氩-5-甲氣基_6_(4_甲基六氩吼喷-1-基)_l-【(8-苯基夺 啉-5-基)胺基羰基]·1Η-吲哚 使用實施例4之類似方法，自5-胺棊-8-苯基喳咁（D66) 和2,3-二氫-5-甲氧基-6-(4-甲基六氫吡畊小基)-1Η-吲哚 (WO95/06672中間物3)製備得黃色/棕色油標題化合物 (20%)。將其自丙酮中轉換成HC1鹽黃色固體。 4 NMR (自由鹼）（250MHz，CDC13) δ (ppm) : 8.95 (dd， 1H)，8·35 (dd，1Η)，7.77-7.65 (m，4Η·)，7.52-7.37 (m，5H)， 6.79 (s，1H)，6·76 (s，1H)，4.25 (t，2H)，3·85 (s，3H)，3.27 (t，2H)，3.14 (br s，4H)，2·66 (br s，4H)，2·37 (s，3H)。 實施例805-氯-2,3-二氩-6·(4_甲基六氩吡畊-1-基)-1·【(8-苯基喳啉-4-基)胺基羰基】_1Η_吲哚 使用實施例2之類似方法，自8-苯基喳啉-4-基異氰酸酯 (D86)和5-氯-2,3-二氫-6-(4_甲基六氫吡畊-1-基)-1Η-吲 111 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閱讀背面之注意事項再· -裝- 本 頁) 訂 -線‘ 509687 A7 B7 五、發明説明（11〇) 哚（D13)製備得黃色固體標題化合物（75〇/0)。 NMR (250MHz，CDC13) δ (ppm) : 8.86 (d，1H)，8.15 (d， 1H)，7·85 (s，1H)，7·77-7·38 (m，9H)，7.19 (s，1H)，4.27 (t， 2H) ’ 3.25 (t，2H) ’ 3.12 (br s，4H)，2.63 (br s，4H)，2.37 (s， 3H)。 ， 實施例81 5-溴-2,3-二氩-6·(4_甲基六氣吡畊基)。-【(心苯基喳啉&amp; 基)胺基羰基】-1Η_弓丨哚 使用貫施例2之類似方法，自心苯基σ奎咐基異氰酸酯 (D86)和臭-2,3_二氫-6-(4•甲基六氫τι比啡]引 哚（D15)製備得黃色固體標題化合物（75〇/〇)。 lR NMR (250MHz, CDC13) δ (ppm) ： 8.87 (d5 1H)，8.16 (d 1H)，7.85 (s，1H)，7.78-7.39 (m，9H)，7·28 (s，1H)，4 29 (t’ 2H)，3.27 (t，2H)，3·11 (br s，4H)，2.63 (br MH)，2 37 i ’ 3H)。 ·（S， 實施例82 2,3-二氩-5-甲氡基-6_(4-甲基六氩吡畊+基)&amp; 啉-4-基)胺基羰基】_1H_吲哚 經濟部智慧財產局員工消費合作社印製 -----------t—— (請先閲讀背面之注意事項再本頁) 、1Τ 線 (D86)和2,3-二氫-5-甲氧基·6件甲基六氣 ^ ^曰 1Η蚓哚（WO 95/06672中間物3)製備棋*龙々 基)· 題化合物（73%)。 1色固體標 lR NMR (250MHz? CDC13) δ (ppm) ： 8.86 (d5 iH), 1H)，7·79-7·38(ιη，9Η)，7.33(s，lH)，6·78(:，1Η ’，8.l9(d， ’ ）’ 4.28 (t， 112 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨〇&gt;&lt;297公釐）· 509687 A7 B7 五、發明説明（ni ) 經濟部智慧財產局員工消費合作社印製 2H)，3.86(s，3H)，3.27(t，2H)，3.14(brs，4H)，2.63(brs， 4H)，2.36 (s，3H)。 實施例835-氯-2,3·二氩小[4-(2,6-二甲基吡啶-4-基)-3-甲基苯基胺 基叛基】-6_(4-甲基六氩峨喷-1_基)_111_弓丨嘴 使用實施例4之類似方法，自4-(2,6-二甲基吡啶-4-基)-3-甲基苯胺（D88)和5-氣-2,3-二鼠-6-(4-甲基六鼠^^-1· 基)-1Η-吲哚（D13)製備得淺黃色固體標題化合物 (41%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 7.82 (s, 1H) ^ 7.36 (d5 2H)，7·31 (dd，1H)，7.20-7.10 (m，2tt)，6·90 (s，2H)，6.46 (s，1H)，4.10(t，2H)，3.18 (t，2H)，3.10(brs，4H)，2.60 (br s，4H)，2·56 (s，6H)，2.35 (s，3H)，2.27 (s，3H)。 實施例845-氯·2,3-二氩-1-[3·甲基-4-(6甲基吡啶-2-基)苯基胺基羰 基】-6-(4-甲基六氩吡畊小基)-1Η-丐丨哚 使用實施例4之類似方法，自3-曱基-4-(6-曱基吡啶-2-基) 苯胺（D89)和5-氣-2,3-二氮-6-(4-曱基六鼠°比啡-1-基)-1Η_ 吲哚（D13)製備得淺黃色膠標題化合物（86%)。將其 自丙酮中轉換成鹽酸鹽淺黃色固體。 4 NMR (250MHz，CDC13) δ (ppm) : 7.83 (s，1H)，7.62 (t， 1H)，7.40-7.28 (m，3H)，7·20-7·14(ιη，2Η)，7.09(d，1Η)， 6·42 (s，1H)，4·10 (t，2H)，3.18 (t，2H)，3·10 (br s，4H)，2·61 (br s，4H)，2.36 (s，3H)，2·35 (s，3H)。 113 本紙張尺度適用中國國家標準（CNS ) A4祝格（210X297公釐) (請先閲讀背面之注意事項再Ιϋ本頁) -裝· 、?τ 線 509687 A7 五、發明説明（112 經濟部智慧財產局員工消費合作社印製 實施例855_澳-2,3-二氩_1-[3_甲基_4咖甲基吡啶4基)苯基胲基羰 基]-6-(4-甲基六氩吼啡-1-基嘴 使用實施例4之類似方法，自3_甲基_4-(6_曱基吡啶_2_基） 苯胺（D89 )和5-溴_2,3-二氫各(4-甲基六氫吡_小基)_1H_ 吲哚（D15)製備得黃色泡沫標題化合物（67%)。將其 自丙酮中轉換成鹽酸鹽米黃色固體。 4 NMR (250MHz，CDC13) δ (ppm) : 7.83 (s，1H)，7.62 (t， 1Η)，7.40-7.28 (m，4H)，7·16 (d，1H)，7·09 (d，1H)，6.42 (s， 1H)，4.10 (t，2H)，3.19 (t，2H)，3.09 (br s，4H)，2.61 (br s， 7H)，2.36 (s，3H)，2.35 (s，3H)。實施例862,3_二氩各甲氧基小[3_甲基_4·(6_甲基吡啶_2_基)苯基胺 基羰基Η-(4_甲基六氫吡呼_1_基)-ιη_吲嗦 使用實施例4之類似方法，自3-甲基-4-(6-甲基吼唆_2_基) 苯胺（D86)和2,3_二氫-5-甲氧基各(4-甲基六氫吡喷小 基)-1Η-吲哚（WO95/06672中間物3)製備得淺黃色泡沫 標題化合物（84%)。將其自丙酮中轉換成鹽酸鹽黃色固 體。 · 4NMR(自由鹼）(250Mife5 CDC13) δ (ppm): 7·71 (s，1H), 7.61 (t，1Η)，7·38-7·28 (m，3Η)，7·16 (d，1Η)，7·〇8 (d，1Η)， 6.72 (s，1H)，6.42 (s5 1H)，4·07 (t，2H)，3·83 (s，3H)，3·18 (t，2H)，3.12 (brs，4H)，2.60(brs，7H)，2.36 (S，3H)，2.34 (s，3H” 114 ^紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐) '' (請先閲讀背面之注意事項再頁) 裝· -訂 線 A7 B7 五、發明説明（113) 實施例87 5-氣-2,3-二氣-1-[5♦甲基吼唆冬基)萘小基胺基羰基】+ (4_甲基六氩吼_小基 使用貫％例4之類似方法，自5_(6_甲基吡唆_2_基)萘 基異氰酸酯（D92)和5-氯-2,3-二氫-6-(4-甲基六氫吡畊-1-基)-1Η^引呼（D13)製備得淺黃色固體標題化合物 (59%)。將其自丙酮中轉換成鹽酸鹽淺黃色固體。 !H NMR (自由鹼）（250MHz，CDC13) δ (ppm) : 7·97 (dd， 1Η)，7·87((1，1Η)，7·85〇，ΐΗ)，7·76-7·68(ηι，2Η)，7·62-7·55 (m，2Η)，7.50-7.40 (m，1Η)，7·33 (d，1Η)，7·23 (d，1Η)， 7.16 (s，1H)，6.80 (s，1H)，4·24 (t，2H)，3.23 (t，2H)，3.09 (br s，4H)，2.67 (s，3H)，2.61 (br s，4H)，2.35 (s，3H)。 實施例88 2,3_二氩-5·甲氧基-1_【5-(6·甲基吡啶-2-基)萘·1_基胺基羰 基】-6-(4-甲基六氩吡喷-l_基)-ΐΗ-吲嗦 使用實施例4之類似方法，自5-(6-甲基吡啶-2-基)萘-1-基異氰酸酯（D92)和2,3-二氫-5-曱氧基-6-(4-甲基六氫吡 畊-1-基)-1Η-吲哚（WO95/06627中間物3)製備得淺黃色 泡沫標題化合物（55%)。將其自丙酮中轉換成鹽酸鹽淺 黃色固體。 4 NMR (自由鹼）（250MHz，CDC13) δ (ppm) : 7.99 (dd， 1H)，7·85 (d，1H)，7·82-7·68 (m，3H)，7·62_7·55 (m，2H)， 7.50-7.41 (m，1H)，7·34 (d，1H)，7.21 (d，1H)，6·76 (s，2H)， 4.24 (t，2H)，3.85 (s，3H)，3.26 (t，2H)，3.15 (br s，4H)，2.67 115 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） ----------裝-- (請先閲讀背面之注意事項再本頁)1T Printed by the Consumer Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 B7 V. Description of the Invention (109) A similar method for printing the Operating Instructions 2 of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs from 5-Qi-2,3- Dihydro small [4-iodophenylaminocarbonyl] -6- (4-methylhexahydropyridin 4-yl) -1H-indole (D43) and 4-pyridineboronic acid (Journal of Medical Chemistry 1997, 40 (22), 3542) The title compound was prepared. Isolation gave the product as a pale yellow solid (46%). lH NMR (250MHz, d6DMSO) δ (ppm): 8.51 (s, 1H), 8.36 (d, 2H), 7.57-7.42 (m, 7H), 7.00 (s, 1H), 3.92 (t, 2H), 2.94 (t5 2H), 2.71 (m5 4H), 2.02 (s, 3H). 4H is masked by the DMSO signal. Example 792,3 · Diargon-5-methylamino-6- (4-methylhexaargin-1-yl) -1-[(8-phenylphosphon-5-yl) aminocarbonyl] · 1Η-indole Using a method similar to that in Example 4, from 5-amine 棊 -8-phenyl 喳 咁 (D66) and 2,3-dihydro-5-methoxy-6- (4-methylhexa Hydropyridine) -1H-indole (WO95 / 06672 Intermediate 3) prepared the title compound (20%) as a yellow / brown oil. It was converted from acetone to a HC1 salt yellow solid. 4 NMR (free base) (250MHz, CDC13) δ (ppm): 8.95 (dd, 1H), 8.35 (dd, 1Η), 7.77-7.65 (m, 4Η ·), 7.52-7.37 (m, 5H) , 6.79 (s, 1H), 6.76 (s, 1H), 4.25 (t, 2H), 3.85 (s, 3H), 3.27 (t, 2H), 3.14 (br s, 4H), 2 · 66 (br s, 4H), 2.37 (s, 3H). Example 805-Chloro-2,3-diargon-6 · (4-methylhexaargin-1-yl) -1 · [(8-phenylphosphonium-4-yl) aminocarbonyl] _1Η _Indole was used in a similar manner to Example 2 from 8-phenylphosphonium-4-yl isocyanate (D86) and 5-chloro-2,3-dihydro-6- (4-methylhexahydropyridine- 1-Base) -1Η-In111 This paper size is applicable to Chinese National Standard (CNS) A4 size (210X297mm) (Please read the precautions on the back before--install-this page) Order-line '509687 A7 B7 5 2. Description of the invention (11) Indole (D13) was used to prepare the title compound (75/0) as a yellow solid. NMR (250MHz, CDC13) δ (ppm): 8.86 (d, 1H), 8.15 (d, 1H), 7.85 (s, 1H), 7.77-7 · 38 (m, 9H), 7.19 (s , 1H), 4.27 (t, 2H) '3.25 (t, 2H)' 3.12 (br s, 4H), 2.63 (br s, 4H), 2.37 (s, 3H). Example 81 5-Bromo-2,3-diargon-6 · (4-methylhexapyridyl). -[(Carboxyphenylphosphonium & yl) aminocarbonyl] -1H-toluene In the same manner as in Example 2, the carbophenyl sulphonyl isocyanate (D86) and odor-2,3_ Dihydro-6- (4 • methylhexahydro-tibiorphine] indole (D15) was used to prepare the title compound (75〇 / 〇) as a yellow solid. LR NMR (250MHz, CDC13) δ (ppm): 8.87 (d5 1H ), 8.16 (d 1H), 7.85 (s, 1H), 7.78-7.39 (m, 9H), 7.28 (s, 1H), 4 29 (t '2H), 3.27 (t, 2H), 3. · 11 (br s, 4H), 2.63 (br MH), 2 37 i '3H). · (S, Example 82 2,3-Diargon-5-methylfluorenyl-6- (4-methylhexapyridine + yl) &amp; chloro-4-yl) aminocarbonyl] _1H_indole economy Printed by the Consumer Cooperatives of the Ministry of Intellectual Property Bureau ----------- t ---- (Please read the precautions on the back before this page), 1T line (D86) and 2,3-dihydro-5 -Methoxy. 6 pieces of methyl hexakis. 1 earthworm indole (WO 95/06672 intermediate 3) Preparation of chrysanthemum). The title compound (73%). Single color solid NMR (250MHz? CDC13) δ (ppm): 8.86 (d5 iH), 1H), 7.79-7 · 38 (ιη, 9Η), 7.33 (s, lH), 6.78 (: ， 1Η ', 8.l9 (d,') '4.28 (t, 112 This paper size applies Chinese National Standard (CNS) A4 specification (2 丨 〇 &gt; &lt; 297 mm) · 509687 A7 B7 V. Description of the invention (Ni) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 2H), 3.86 (s, 3H), 3.27 (t, 2H), 3.14 (brs, 4H), 2.63 (brs, 4H), 2.36 (s, 3H) Example 835-Chloro-2,3 · diargon [4- (2,6-dimethylpyridin-4-yl) -3-methylphenylaminoalkyl] -6- (4-methyl Hexagonal argon spray-1_yl) _111_bow 丨 A similar method as in Example 4 was used, starting from 4- (2,6-dimethylpyridin-4-yl) -3-methylaniline (D88) and 5 The title compound (41%) was prepared as a pale yellow solid from -Ga-2,3-dimur-6- (4-methylhexamur ^^-1 · yl) -1H-indole (D13). LH NMR (250MHz , CDC13) δ (ppm): 7.82 (s, 1H) ^ 7.36 (d5 2H), 7.31 (dd, 1H), 7.20-7.10 (m, 2tt), 6.90 (s, 2H), 6.46 ( s, 1H), 4.10 (t, 2H), 3.18 (t, 2H), 3.10 (brs, 4H), 2.60 (br s, 4H), 2.56 (s, 6H), 2 .35 (s, 3H), 2.27 (s, 3H). Example 845-Chloro-2,3-diargon-1- [3-methyl-4- (6methylpyridin-2-yl) phenyl Aminocarbonyl] -6- (4-methylhexapyridinyl) -1Η-benzylindole Using a method similar to that in Example 4, from 3-fluorenyl-4- (6-fluorinylpyridine-2- Group) aniline (D89) and 5-air-2,3-diazine-6- (4-fluorenylhexamur °° biffin-1-yl) -1Η_indole (D13) to prepare the title compound as a pale yellow gum ( 86%). It was converted into the hydrochloride pale yellow solid from acetone. 4 NMR (250MHz, CDC13) δ (ppm): 7.83 (s, 1H), 7.62 (t, 1H), 7.40-7.28 (m, 3H), 7.20-7 · 14 (ιη, 2Η), 7.09 (d, 1Η), 6.42 (s, 1H), 4 · 10 (t, 2H), 3.18 (t, 2H), 3 · 10 (br s, 4H), 2.61 (br s, 4H), 2.36 (s, 3H), 2.35 (s, 3H). 113 This paper size applies the Chinese National Standard (CNS) A4 Zhuge (210X297 mm) (Please read the precautions on the back before this page)-Installation ·,? Τ Line 509687 A7 V. Invention Description (112 Wisdom of the Ministry of Economic Affairs Example 855_Australia-2,3-Diargon_1- [3-methyl_4methylpyridine 4-yl) phenylfluorenylcarbonyl] -6- (4-methyl Hexaargin-1-yl mouth was similar to that used in Example 4, starting from 3-methyl_4- (6_amidinopyridin_2_yl) aniline (D89) and 5-bromo_2,3-di Hydrogen (4-methylhexahydropyridyl) _1H_indole (D15) was prepared as a yellow foam title compound (67%). It was converted from acetone to the hydrochloride beige solid. 4 NMR (250MHz, CDC13) δ (ppm): 7.83 (s, 1H), 7.62 (t, 1Η), 7.40-7.28 (m, 4H), 7.16 (d, 1H), 7.09 (d, 1H), 6.42 ( s, 1H), 4.10 (t, 2H), 3.19 (t, 2H), 3.09 (br s, 4H), 2.61 (br s, 7H), 2.36 (s, 3H), 2.35 (s, 3H). Implementation Example 862, 3_diargon each methoxy small [3-methyl_4 · (6_methylpyridin_2_yl) phenylaminocarbonylfluorene- (4-methylhexahydropyridine_1_ ) -Ιη_indene using Example 4 Similar method, from 3-methyl-4- (6-methylpyridin-2-yl) aniline (D86) and 2,3-dihydro-5-methoxy (4-methylhexahydropyridine) Small group) -1Η-indole (WO95 / 06672 intermediate 3) prepared the title compound as a pale yellow foam (84%). It was converted from acetone to the hydrochloride yellow solid. · 4NMR (free base) (250Mife5 CDC13 ) δ (ppm): 7.71 (s, 1H), 7.61 (t, 1Η), 7.38-7 · 28 (m, 3Η), 7.16 (d, 1Η), 7.08 (d , 1Η), 6.72 (s, 1H), 6.42 (s5 1H), 4.07 (t, 2H), 3.83 (s, 3H), 3.18 (t, 2H), 3.12 (brs, 4H) , 2.60 (brs, 7H), 2.36 (S, 3H), 2.34 (s, 3H "114 ^ Paper size applies to China National Standard (CNS) A4 specification (210X297 mm) '' (Please read the precautions on the back before Page) Assembly ·-Binding line A7 B7 V. Description of the invention (113) Example 87 5-Gas-2,3-Digas-1- [5 ♦ methylnaphthyl) naphthylaminoaminocarbonyl] + (4-Methylhexahydroxanyl group was used in a similar manner as in Example 4 from 5- (6_methylpyridin-2-yl) naphthyl isocyanate (D92) and 5-chloro-2,3-di Hydrogen-6- (4-methylhexahydropyridin-1-yl) -1Η ^ Introduction (D13) to prepare light yellow Of the title compound (59%). It was converted from acetone to the hydrochloride salt as a pale yellow solid. ! H NMR (free base) (250 MHz, CDC13) δ (ppm): 7.97 (dd, 1Η), 7.87 ((1, 1Η), 7.85〇, ΐΗ), 7.76-7 · 68 (η, 2Η), 7.62-7.55 (m, 2Η), 7.50-7.40 (m, 1Η), 7.33 (d, 1Η), 7.23 (d, 1Η), 7.16 (s , 1H), 6.80 (s, 1H), 4.24 (t, 2H), 3.23 (t, 2H), 3.09 (br s, 4H), 2.67 (s, 3H), 2.61 (br s, 4H), 2.35 (s, 3H). Example 88 2,3_Diargon-5 · methoxy-1_ [5- (6 · methylpyridin-2-yl) naphthalene · 1-ylaminocarbonyl] -6- (4-methylhexagon Pyridine-l-yl) -fluorene-indionium Using a method similar to that in Example 4, from 5- (6-methylpyridin-2-yl) naphthalene-1-yl isocyanate (D92) and 2,3-dihydro -5-Methoxy-6- (4-methylhexahydropyridin-1-yl) -1fluorene-indole (WO95 / 06627 intermediate 3) prepared the title compound (55%) as a pale yellow foam. It was converted from acetone to the hydrochloride salt as a pale yellow solid. 4 NMR (free base) (250MHz, CDC13) δ (ppm): 7.99 (dd, 1H), 7.85 (d, 1H), 7.82-7 · 68 (m, 3H), 7.62_7 · 55 (m, 2H), 7.50-7.41 (m, 1H), 7.34 (d, 1H), 7.21 (d, 1H), 6.76 (s, 2H), 4.24 (t, 2H), 3.85 (s , 3H), 3.26 (t, 2H), 3.15 (br s, 4H), 2.67 115 This paper size is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) ---------- pack- -(Please read the notes on the back before this page)

、1T 線_ 經濟部智慧財產局員工消費合作社印製 509687 A7 B7 經濟部智慧財產局員工消費合作社印製 發明説明（114) (br s，7H)，2.38 (s5 3H)。 實施例89 5-氯_2,3_二氩_卜(4_ &amp;基六氩吡喷^基)小[4_(吡啶_4基） 茶-1-基胺基叛基】嘴 使用實施例4之類似方法，自4_(吡啶_4_基）萘_丨_基胺 (D2)和5-氣-2,3-二氫-6-(4-乙基六氫〇比σ井_ 1 -基H-令朵 (D97)製備得米黃色固體標題化合物。自丙酮 中單離得其HC1鹽黃色固體。 4 NMR(自由鹼）(250MHz，CDC13) δ (ppm): 8.74 (d，2Η)， 8.00 (d，1H)，7·91 (s51H)，7·91-7·86 (m，2H)，7.61-7.42 (m， 5H)，7.19 (s，1H)，6.81 (s，1H)，4.30 (t，2H)，3.28 (t，2H)， 3·11 (br s，4H)，2.62 (br s，4H)，2.48 (q，2H)，U1 (t5 3H)。 實施例905_氯-2,3_二氩_6_(4_乙基六氩吡畊4基)小【5-(吼啶+基) 茶-1-基胺基援基】_im鳴 使用實施例4之類似方法，自5-(吡啶-4-基)萘-1-基胺 (D74)和5-氯-2,3·二氫-6-(4-乙基六氫吼4-1-基)-1Η-吲 哚（D97)製備得米黃色固體標題化合物（68%)。自丙 酮中單離得其HC1鹽黃色固體。 4 NMR(自由驗）(250MHz，CDC13) δ (ppm): 8.74 (d，2H)， 8.02(d，1H)，7.84(s，1H)，7.77(d，1H)，7.71 (d，1H)，7·60 (t，1H)，7.49(t，1H)，7.45-7.41 (m，3H)，7.19 (s，1H)，6·73 (s，1H)，4·28 (t，2H)，3·27 (t，2H)，3.09 (br s，4H)，2.60 (br s，4H)，2·46 (q，2H)，1.09 (t，3H)。 116 (請先閲讀背面之注 意事項再^本頁 裝· -訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210x297公釐） 509687 A7 __B7 五、發明説明（115) 經濟部智慧財產局員工消費合作社印製 實施例91 S·氯_2,3_二氩-6_(六氣咄畊小基)小丨4-(吼啶冰基)萘士基 胺基羰基】-1H-吲哚廬酸盥 將溶於甲醇（30毫升）之經攪拌6_[冬(第三_丁氧基羰基) 六氫吡畊-1-基]氣-2,3-二氫-ΐ·[4-(哄啶冰基)萘-1_基胺 基羰基]-111_吲哚（Dl〇〇，345毫克，0.59毫莫耳）溶液， 以溶於醚（3毫升）中之1MHC1處理。待經於室溫下18 小時後，將額外溶於醚（2.5毫升）中之HC1加入。待經 24小時後，將此混合物於真空中濃縮，並將殘餘物藉由 與丙酮研磨而固化，獲得黃色固體標題化合物（260毫 克，84%)。 !H NMR (250MHz, d6DMSO) δ (ppm) ： 9.32 (s, 2H) ^ 9.09 (s5 1H)，9.04 (d，2H)，8.23-8· 19 (m，3H)，7.88 (dd，1H)，7·77-7·59 (m，5H)，7.30 (s，1H)，4.37 (t，2H)，3.24-3.18 (m，6H)，3.10 (br s，4H)。 實施例92 S-氣·2,3_^-氮-6_(六氣吼喷-1_基)-1-[5-(峨咬_4_基)茶-1_基 胺基羰基HH-吲哚盥酸躉 使用實施例91之類似方法，自6-[4-(第三-丁氧基羰基)六 氫吡畊小基]-5-氣-2,3_二氫小[4-(吼啶-4-基)萘小基胺基 羰基]-1Η-吲哚（D100)製備得米黃色固體標題化合物 (60%)。 lU NMR (250MHz, d6DMSO) δ (ppm) ： 9.41 (s, 2H) &gt; 9·17_9·13 (m，3H)，8·37_8·28 (m，3H)，7.84-7.64 (m，6H)， 117 (請先閲讀背面之注意事項再本頁) |裝· 太 訂 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） JUy〇6/ A7 --— _ B7五、發明説明（116 ) 經濟部智慧財產局員工消費合作社印製 =〇 (s，1H)，4.45 (t，2H)，3·35-3·26 (m，6H)，3· 19 (br s，4H)。 實施例935分氯-2,3_二氩-6_(4_甲基六氩吼和·基)邻(塔讲各基) 苯基胺基羰基HH-吲哚 使用說明1之類似方法，自外岭3_基)苯甲酸（D1〇2) 所製備標題化合物形成異氰酸酯，隨後將5_氯_2,3_二氫一 6-(4-甲基六氫吡畊吲哚（d13)加入，獲得淺 黃色固體尿素（7%)。HNMR(25(MHz，CDC13) δ (ppm) : 9.12 (dd，1H)，8.06(d， 2H) ’ 7.82 (m，2H) ’ 7·61 (d，2H) ’ 7·51 (m，1H)，7·14 (s，1H)， 4.12(t，2H) ’ 3.19(t，2H)，3.11(brs，4H)，2.61(brs，4H)， 236 (s5 3H) 〇 實施例94心澳_2,3_二氩_6-(4-甲基六氩吡畊-1-基)_l-[4-(嗒喷-3-基) 苯基胺基羰基】-1H-弓丨哚使用說明1之類似方法，自4十比啶各基)笨甲酸（D1〇2) 所製備標題化合物形成異氰酸酯，隨後將5_溴_2,3_二氫_甲基六氫π比u井小基哚（D15)加入，獲得灰 色固體尿素（3%)。 又 NMR(250MHz,CDC13)δ (ppm) ： 9.12(dd51H) ^ 8.08(d, 2H)，7·83 (m，2H)，7.62 (d，2H)，7.52 (m，1H)，7·34 (s，1H)， 6·6〇 (MH)，4.13 (t，2H)，3·20 (t，2H)，3·1〇 (br s，4H)，2·61 (br s，4H)，2·36 (s，3H)。 實施例95 118Line 1T_ Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (114) (br s, 7H), 2.38 (s5 3H). Example 89 5-Chloro_2,3_diargon_b (4_ &amp; Hexylpyridinyl) small [4_ (pyridin_4yl) tea-1-ylaminomethyl] Example of mouth use A similar method of 4, from 4- (pyridine_4_yl) naphthalene_ 丨 _ylamine (D2) and 5-gas-2,3-dihydro-6- (4-ethylhexahydro) than σ well_ 1 -H-Ringdo (D97) prepared the title compound as a beige solid. The HC1 salt yellow solid was isolated from acetone. 4 NMR (free base) (250MHz, CDC13) δ (ppm): 8.74 (d, 2Η ), 8.00 (d, 1H), 7.91 (s51H), 7.91-7 · 86 (m, 2H), 7.61-7.42 (m, 5H), 7.19 (s, 1H), 6.81 (s, 1H ), 4.30 (t, 2H), 3.28 (t, 2H), 3.11 (br s, 4H), 2.62 (br s, 4H), 2.48 (q, 2H), U1 (t5 3H). Example 905 _Chloro-2,3_Diargon_6_ (4_Ethylhexagonopyridyl 4 group) Small [5- (anhydropyridine + yl) tea-1-ylamino group] _imming using Example 4 of Similar method, from 5- (pyridin-4-yl) naphthalen-1-ylamine (D74) and 5-chloro-2,3 · dihydro-6- (4-ethylhexahydro-4-yl) -1Η-indole (D97) prepared the title compound as a beige solid (68%). The HC1 salt yellow solid was isolated from acetone. 4 NMR (free test) (250 MHz, CDC13) δ (p pm): 8.74 (d, 2H), 8.02 (d, 1H), 7.84 (s, 1H), 7.77 (d, 1H), 7.71 (d, 1H), 7.60 (t, 1H), 7.49 (t , 1H), 7.45-7.41 (m, 3H), 7.19 (s, 1H), 6.73 (s, 1H), 4.28 (t, 2H), 3.27 (t, 2H), 3.09 (br s, 4H), 2.60 (br s, 4H), 2.46 (q, 2H), 1.09 (t, 3H). 116 (Please read the notes on the back before ^ This page is installed.--The size of the paper is applicable China National Standard (CNS) A4 specification (210x297 mm) 509687 A7 __B7 V. Description of invention (115) Example 91 printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economy 91 S · Chlorine_2,3_Diargon-6_ (Six Pneumatic farming small group) small 丨 4- (Cyclobutyryl) naphthylaminocarbonyl group] -1H-indole acid will be dissolved in methanol (30 ml) after stirring 6_ [冬 (第二 _ 丁(Oxycarbonyl) hexahydropyridin-1-yl] gas-2,3-dihydro-fluorene · [4- (oxidylbenzyl) naphthalene-1-ylaminocarbonyl] -111_indole (DlO (0,345 mg, 0.59 mmol) was treated with 1 MHC1 in ether (3 ml). After 18 hours at room temperature, additional HC1 dissolved in ether (2.5 ml) was added. After 24 hours, the mixture was concentrated in vacuo, and the residue was solidified by triturating with acetone to obtain the title compound (260 mg, 84%) as a yellow solid. ! H NMR (250MHz, d6DMSO) δ (ppm): 9.32 (s, 2H) ^ 9.09 (s5 1H), 9.04 (d, 2H), 8.23-8 · 19 (m, 3H), 7.88 (dd, 1H) , 7.77-7.59 (m, 5H), 7.30 (s, 1H), 4.37 (t, 2H), 3.24-3.18 (m, 6H), 3.10 (br s, 4H). Example 92 S-Ga · 2,3 _ ^-Nitrogen-6_ (Six-Gas Spray-1_yl) -1- [5- (Ebitrate_4_yl) Tea-1_ylaminocarbonylHH-ind Indol acid was used in a similar manner as in Example 91, starting from 6- [4- (third-butoxycarbonyl) hexahydropyridine] -5-Ga-2,3-dihydro small [4- ( Amidin-4-yl) naphthylaminoaminocarbonyl] -1H-indole (D100) prepared the title compound (60%) as a beige solid. lU NMR (250MHz, d6DMSO) δ (ppm): 9.41 (s, 2H) &gt; 9.17_9 · 13 (m, 3H), 8.37_8 · 28 (m, 3H), 7.84-7.64 (m, 6H) , 117 (Please read the precautions on the back first, and then this page) | Packing · The size of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) JUy〇6 / A7 --- _ B7 V. Description of the invention (116) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs = 0 (s, 1H), 4.45 (t, 2H), 3.35-3.26 (m, 6H), 3.19 (br s, 4H) . Example 935 Chlorin-2,3_diargon-6_ (4-methylhexaarginyl group) o- (tall group) PhenylaminocarbonylHH-indole Using a similar method as in Note 1, since The title compound prepared from Wailing 3-yl) benzoic acid (D102) forms an isocyanate, and then 5-chloro_2,3_dihydro-6- (4-methylhexahydropyridine indole (d13) is added to , To obtain light yellow solid urea (7%). HNMR (25 (MHz, CDC13) δ (ppm): 9.12 (dd, 1H), 8.06 (d, 2H) '7.82 (m, 2H)' 7.61 (d , 2H) '7.51 (m, 1H), 7.14 (s, 1H), 4.12 (t, 2H)' 3.19 (t, 2H), 3.11 (brs, 4H), 2.61 (brs, 4H), 236 (s5 3H) 〇 Example 94 Xinao_2,3_diargon-6- (4-methylhexapyridin-1-yl) _l- [4- (Daquan-3-yl) phenyl Aminocarbonyl] -1H-toxin Indole was used in a similar manner to Note 1 to form the isocyanate from the title compound prepared from 4-decapyridinyl) benzylcarboxylic acid (D102), and then 5-bromo_2,3_di Hydrogen-methyl hexahydrogen π was added to U-well small base indole (D15) to obtain gray solid urea (3%). Also NMR (250MHz, CDC13) δ (ppm): 9.12 (dd51H) ^ 8.08 (d, 2H) , 7.83 (m, 2H), 7.62 (d, 2H), 7.52 (m, 1H), 7 · 34 (s, 1H), 6.60 (MH), 4.13 (t, 2H), 3.20 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 4H ), 2.36 (s, 3H). Example 95 118

(請先閲讀背面之注意事項再本頁) 裝· 線_ B7 五、發明説明（117) 5_氣_2,3_二氩_6_(4_甲基六氣吡畊小基)+[4_(吡畊：基) 苯基胲基羰基】-1Η_吲哚 使用說明1之類似方法，自4_(σ比畊各基)苯甲酸（ό1〇3) 所製備標題化合物形成異氰酸酯，隨後將5_氣_2，孓二氫一 6-(4-甲基六氫吡畊小基)_11{蚓哚（D13)加入，獲得淺 黃色固體尿素（30%)。 · HNMR(250MHz，CDC13) δ (ppm) : 9·01 (s，1H)，8.61 (s， 1Η)，8·47 (d，1Η)，8·02 (d，2Η)，7·83 (s，1Η)，7·61 (d，2Η)， 7·16 (s，1H) ’ 6.55 (s，1H)，4.13 (t5 2H)，3.20 (t，2H)，3·11 (br s，4H)，2·61 (br s，4H)，2·36 (s，3H)。 實施例96 5- 溴_2,3_二氩-6_(4_甲基六氩吡畊士基)小[4(吡矫2基) 苯基胺基羰基1-1H_吲哚 使用說明1之類似方法，自4十比畊-3-基)苯甲酸（D103) 所製備標題化合物形成異氰酸酯，隨後將孓溴-2,3_二氫 6- (4-甲基六氫吡畊小基)-出_吲哚（D15)加入，獲得产 黃色固體尿素（30%)。 ^ 'H NMR (250MHz, CDC13) δ (ppm) ： 9.00 (s5 1H) ^ 8.6〇 (s 經濟部智慧財產局員工消費合作社印製 1H) ’ 8·48 (d，1H)，8.01 (d，2H)，7·83 (s，1H)，7.61 (d，2H)，’ 7.34 (s，1H)，6.57 (s，1H)，4·13 (t，2H)，3.20 (t，2H)，3 1〇 (br s，4H)，2.62 (br s，4H)，2.36 (s，3H)。 實施例97 S-氣_2,3_二氩-6-(4-甲基六氣吡畊+基)小【(2·苯基吡咬^ 基)胺基羰基HH-吲哚 ^ 119 本紙張尺度適用中國國家標準（(：叫八4祕（21〇^297公釐） 509687 A7 B7 五、發明説明（118 ) 使用說明1之類似方法，自6-苯基煙酸（D104)所製備 標題化合物形成異氰酸酯，隨後將5_氯_2,3_二氫-6-(4_甲 基六氫吡畊小基)-1Η_吲哚（D13)加入，獲得白色固體尿 素（48%)。 !HNMR (250MHz, d6DMSO) δ (ppm) ： 8.87 (dd, 2Η) , 8 l2 (m，3H)，7·96 (d，1H)，7.83 (s51H)，7.47 (m，3H)，7·28 (s 1H) ’，4·22 (t，2H) ’ 3·17 (t，2H)，2·95 (br s，4H)，2.54 (br s 受到 DMSO 峰遮蔽，4H)，2.26 (s，3H)。 實施例98 S-淡-2,3-二氩-6-(4-甲基六氩吡+i-基)小[(2-苯基吡唆a 基)胺基羰基HH_吲哚 ~ 使用說明1之類似方法，自6_苯基煙酸（D1〇4)所製備 標題化合物形成異氰酸酯，隨後將5_溴_2,3_二氫_6_(4_甲 基六氫吼畊-1_基)-1沁吲哚（D15 )加入，獲得純白色固體 尿素（46%)。 · 經濟部智慧財產局員工消費合作社印製 !H NMR (250MHz, d6DMSO) δ (ppm) ： 8.86 (dd, 2Η) ^ 8.12 (m5 3H)，8.09 (d，1H)，7·83 (s，1H)，7·47 (m，4H)，4·22 (t， 2H)，3·18 (t，2H)，2.94 (br s5 4H)，2·53 (br s，受到 DMSO 峰遮蔽，4H)，2.26(s，3H)。 · 實施例99 5-氣_2,3-二氣+㈣卜甲基嗒畊各基)苯基胺基羰基】·6普 甲基六氣吡啡-1-基)-1Η-啕哚 使用說明1之類似方法，自4_(6_肀基嗒畊_3_基)苯甲酸 (D105)所製備標題化合物形成異氰酸酯，隨後將孓氣 120 509687 A7 B7 經濟部智慧財產局員工消費合作社印製 五、發明説明（119) -2,3-二氮-6-(4-甲基六氮 σ比11 井-1-基( D13 )加入， 獲得米色固體尿素（23%)。 lH NMR (250MHz, CDC13) δ (ppm) ： 8.03 (d5 2H) ^ 7.83 (s? 1H)，7.35 (d，1H)，7.14 (s，1H)，6.59 (s，1H)，4.11 (t，2H)， 3.18(t，2H)，3.11(brs，4H)，2.74(s，3H)，2.60(brs，4H)， 2.36 (s，3H)。 實施例1005_澳_2,3_二氮-l-[4-(6-甲基塔味_3_基)苯基胺基擬基】_6-(4_ 甲基六氩吡畊小基)-1Η_弓丨哚 使用說明1之類似方法，自4-(6·曱基嗒畊-3-基)苯曱酸 (D105)所製備標題化合物形成異氰酸酯，隨後將5-溴 -2,3-二氫-6-(4-甲基六氫吡4-1-基)_1H-吲哚（D15 )加入， 獲得米色固體尿素（28%)。 4 NMR (250MHz，CDC13) δ (ppm) : 8.05 (d，2H)，7.84 (s， 1H)，7.72 (d，1H)，7.60 (d，2H)，7·35 (m，2H)，6.57 (s，1H)， 4.13 (t，2H)，3.20 (t，2H)，3.10 (br s，4H)，2.75 (s，3H)，2.62 (br s，4H)，2·36 (s，3H)。 實施例1015-氣-2,3-二氩-6-(4_甲基六氩吡基)-l-[4-(吡啶-3-基) 苯基胺基羰基〗-1Η-吲哚 使用說明2之類似方式’自5-氣-2,3-二氮-1-(4-峨苯基胺 基羰基)-6-(4-甲基六氫吡畊小基)-1Η-吲哚（D43)和3-吡啶硼酸（化學物理通報，1983，31(12)，4573)製備標 題化合物，獲得淺奶油色粉末（19%)。 121 (請先閱讀背面之注意事項再本頁) .裝· -!·%&gt; 線_ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 509687 A7 B7 - 1 五、發明説明（120 ) !HNMR(250MHz, d6DMSO) δ (ppm) ： 8.81 (s, 1H) ^ 8.61 (s5 1H)，8.45 (d，1H)，7.96 (d，1H)，7·7 〇, 1H)，7.62 (m，4H) ’ 7.14(s，1H)，4.08(t，2H) , 3.04(t，2H)，2.83(brs，4H)，2.15 (s，3H)。2xCHJfl號受到DMSO訊號遮蔽。 實施例102 5- 氯-2,3-二氩_1_[4_(5·甲基噚邊_2-基)苯基胺基叛基Η_(4_ 甲基六氩吡啡-1-基)-1Η_吲哚 使用實施例4之類似方法，自5-氣-2,3-二氫-6-(4-甲基六 氫口比井小基卜朵（D13)和4_(5-甲基1坐冬基)本胺 (D107)製備標題化合物，獲得淺奶油色粉末（63%)。 NMR (250MHz，d6DMSO) δ (ppm): 8.78 (s，1Η)，7.72 (m， 5H)，7.20 (s51H)，6·90 (s，1H)，4·14 (t，2H)，3·08 (t，2H)， 2.96 (br s，4H)，2.72 (brs，4H)，2.38(s，3H)，2.33(s，3H)。 實施例103 2,3-二氫-5·甲氧基_l-【4-(5-甲基噚吐-2-基)苯基胺基羰基】- 6- (4-甲基六氩吡畊-1-基)-1Η-弓丨哚 使用實施例4之類似方法，自2,3-二氫-5-曱氧基·6·(4-曱 基六氫吡畊小基)-1Η-吲哚（WO 95/06627中間物3)和 4-(5-甲基啐唑-2-基)苯胺（D107)製備標題化合物，獲得 淺奶油色粉末（44%)。 lH NMR (250MHz, d6DMSO) δ (ppm) ： 8.80 (s, 1H) ^ 7.97 (d5 2H)，7·86 (d，2H)，7·77 (s，1H)，7·08 (s，1H)，7·00 (s，1H)， 4.27 (t，2H)，3·89 (s，3H)，3.25 (t，2H)，3·07 (br s，4H)，2.61 (br s，7H)，2.52 (s，3H)，2·37 (s，3H)。 122 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） --------- _ 裝^_ I (請先閱讀背面之注意事項再本頁) 訂 線 經濟部智慧財產局員工消費合作社印製 、發明説明（121 經濟部智慧財產局員工消費合作社印製 實施例104 S_澳-2,3_二氬-1_【4-(5_甲基畤峻_2_基)苯基胺基羰基】_6分 甲基六氩吡畊-1-基)_im鳴 ，用貫施例4之類似方法，自5_溴_2,3_二氫(冬曱基六 氫咖井-1_基)-1Η-吲哚（DI5)和4_(5_曱基畤唑冬基)苯胺 i(D107)製備標題化合物，獲得淺奶油色粉末（23%)。 H NMR (250MHz，CDC13) δ (ppm) : 7.94 (d，2H)，7·82 (s， 1Η) ’ 7·52 (d，2Η) ’ 7·33 (s，1Η)，6.81(s，1Η)，6·58 (d，1Η)， 4.11 (t，2H)，3.15 (m，6H)，2.69 (br s，4H)，2.42 (s，3H)， 2.39 (s，3H)。 實施例105 s-氣-2,3-二氫小[4介甲基吡唑_4基)苯基胺基羰基】_6(4_ 甲基六氩吡畊小基)_1H-吲鳴 使用說明1之類似方法，自4仆甲基*坐斗基)苯甲酸 (WCW/43%2)所製備標題化合物形成異氰酸自旨，隨後 將5-氣二氫_6‘(4_甲基六氫咄畊小基)_m_吲。朵 /D13)加入，獲得純白色固體尿素（18%)。 H NMR (250MHz，CDC13) δ (ppm&gt; : 7 82 (s，1H)，7 s 1H)，7.55 (s，1H)，7·41 (s，4H)，7 13 (s，m)，6 44 &amp; ih)，， 4·〇7 (t，2H)，3·93 (S，3H)，3·16 (t5 2H)，3·1() (br s，4H)，2 6〇 (br s，4H)，2·35 (s，3H)。 實施例106 &amp;澳-2,3-二氣-1*(1-甲基料冰基)苯基胺基幾基】终 甲基六氣吨喷-1_基丨鳴 123 本紙張尺度適财關家％竿（CNS ) Α4· ( 210X297公楚丁 (請先閲讀背面之注意事項再頁) 裝· 、1Τ 線 509687 A7 B7 經濟部智慧財產局員工消費合作社印製 五、發明説明（122) 使用說明1之類似方法，自4-(1-曱基吡唑-4-基)苯甲酸 (W097/43262)所製備標題化合物形成異氰酸酯，隨後 將5-溴-2,3_二氫-6-(4-甲基六氫吡啡-1-基)-1Η-吲哚 (D15)加入，獲得米色固體尿素（30%)。 !H NMR (250MHz，CDC13) δ (ppm) : 7.83 (s，1H)，7.71 (s， 1H)，7·54 (s，1H)，7·40 (s，4H)，7·31 (s，1H)，6.46 (s，1H)， 4.05 (t，2H)，3.93 (s，3H)，3.15 (t，2H)，3.08 (br s5 4H)，2.60 (br s，4H)，2.35 (s，3H)。 實施例107 5_氟氰基甲基聯苯基-4_基胺基羰基】-2,3_二氩-6-(4_甲基六氩吡畊小基)-1Η-吲哚 使用說明1之類似方法，自4-(4-氰基各甲基笨基)苯曱酸 (D106)所製備標題化合物形成異氰酸酯，隨後將5-氯 -2,3-二氮-6_(4-甲基六氮吼〇井-1-基朵（D13 )加入’ 獲得淺黃色固體尿素（39%)。 4 NMR (250MHz，CDC13) δ (ppm) : 7.82 (s，1H)，7.64 (d， 1H)，7.44-7.55 (m，6H)，7·15 (s，1Η)，6.52 (s，1Η)，4·11 (t， 2H)，3.19(t，2H)，3.10(brs，4H)，2.60(brs，4H)，2.35(s， 3H)。 實施例108 5_溴氰基-3f_甲基聯苯基-4_基胺基羰基】_2,3-二氩_6-(4-甲基六氩吡畊-1-基)-1Η-吲哚 使用說明1之類似方法，自4-(4-氰基-3-甲基苯基)苯曱酸 (D106)所製備標題化合物形成異氰酸酯，隨後將5-溴 124 —---------裝^-- (請先閱讀背面之注意事項再mb本頁) 訂 -線 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X297公釐） 509687 A7 B7 五、發明説明（123 -2,3-二氫-6-(4-甲基六氫吡畊_ι_基)]h-吲哚（D15)加入， 獲得淺黃色固體尿素（28%)。 H NMR (250MHz，CDC13) δ (ppm) : 7.83 (s，1H)，7.64 (d， 1H)，7·42-7·55(ηι，6Η)，7.33(s，1H)，6.54(s，1H)，4.10(t， 2H) ’ 3.18 (t，2H)，3.08(brs，4H)，2.60 (brs，4H)，2.35 (s， 3H) 〇 實施例109 5-氣_2,3_二氩小[4_(2_甲基吡唆_5_基)苯基胺基羰基】-6·(4-甲基六氩吡畊_1_基)_1Η_吲哚 使用說明1之類似方法，自4-(2,曱基吡啶-5-基)苯甲酸 (WO 97/43262)所製備標題化合物形成異氰酸酯，隨後 將5-氯-2,3-二氫-6-(4-甲基六氫σ比啡_ι_基)_i私u引哚 (D13)加入，獲得米色固體尿素（2%)。 H NMR (250MHz，CDC13) δ (ppm) : 8·68 (d，1H)，7 82 (s 6.50 (s, 1H). 4.11 (t, 2H) &gt; 3.18 (t, 2H)，3.11 (br s, 4H) &gt; 2.59 (br s，7H)，2·36 (s5 3H)。 實施例110 經濟部智慧財產局員工消費合作社印製 5-決-2,3-二甲基吼唆·5_基)苯基胺基叛基】邻· 甲基六氣吼喷_1·基嘴 使用說们之類似方法，自心㈣基终5·基)苯甲酸 =097/4遍）㈣備標題化合物形成異氰酸酷， 將-漠-2,3-二氫邻_甲基六氫外咖 (D15)加入，獲得米色固體尿素（1〇%)。 125 本紙張尺度適用中國國家標準（CNS ) A4規格f21〇X29$Jy 509687 經濟部智慧財產局員工消費合作社印製 五、發明説明（124 4 NMR (250MHz，d6DMS0) δ (ppm): 8 79 (d，1H)，&amp; 1H)，7.99 (dd，1H)，7·84 (s，ιΗ)，7 71 (q，4H), 7 43 (s，1Ή), ’ 7.36 (d，1H)，4·21 (t，2H)，3el7 (t，2H)，2.96 (br s，4H)， 2.54(brs，受到 DMSO 峰遮蔽，7H)，2 31 (S，3H)。 實施例111 5-氣以-工氩-叩分甲基义从畤二唑各基读+基膝 基叛基】-6-(4_甲基六氣吼呼 使用實施例4之類似方式，自5-氣-2,3-二氫-6-(4-甲基六 氫吡畊小基朵（D13)和5-(3-甲基·1，2,4巧二也 5_基)萘小基胺（Dill)製備標題化合物。將標題化合物 轉換成其鹽酸鹽淺黃色粉末（59%)。 iNMR (HC1 鹽）(250MHz，d6DMSO” (ppm) : ΐ〇·82(δ 1H)，9·03 (s，1Η)，8·92 (d，1H)，8.42 (m，2H)，7.78-7.65 (m 4H)，7·31 (s，1H)，4·34 (t，2H)，3.48-2.94 (m，10H)，2.80 (d 3H)，2.54 (s，3H)。 ’ 實施例112 2,3_«—氣-5-甲氣基-l-[5-(3_ 甲基-1，2,4_今二嗅基)茶_1_ 基胺基羰基】_6_(4_甲基六氣吡喷-1-基)_1H_吲哚 使用實施例4之類似方式，自2,3-二氫-5-甲氧基_6_(4_甲 基六氫吡畊小基)-1Η-吲哚（WO 95/06627中間物3)和 5-(3-甲基-1，2,4-4二唑·5-基)萘小基胺（Dill)製備標題 化合物。將標題化合物轉換成其鹽酸鹽無色粉末（68%)。 4 NMR ( HC1 鹽）（250MHz，d6DMSO) δ (ppm) : 10.87 (s， 1H)，8.92 (s，1H)，8.87 (d，1H)，8.41-8.33 (m，2H)，7·78麵 126 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐）. (請先閲讀背面之注意事項再|1|^本頁} .裝· -訂 線 509687 A7 ____B7 五、發明説明（125 ) 經濟部智慧財產局員工消費合作社印製 7·65 (m，3H)，7.60 (s，1H)，6.94 (s51H)，4·30 (t，2H)，3·77 (s，3H)，3.40 (m，4H)，3·2〇 (m，4H)，2.89 (t，2H)，2·75 (d， 3H)，2.53 (s，3H)。 實施例1135-澳 _2,3-二氩-1_[5-(3-甲基 二唑·5_ 基)萘-1-基胺 基叛基】-6_(4·甲基六氣吼吩4-基)-1Η_啼嗦 使用實施例4之類似方式，自5_溴_2,3_二氫-6-(4-曱基六 氫吡畊-1-基)-1H-吲哚（D15)和5-(3甲基-1，2,4_啐二吐-5-基)萘-1_基胺（Dili)製備標題化合物。將標題化合物 轉換成其鹽酸鹽淺米色粉末（36%)。 lHNMR (HCm) (250MHz, d6DMSO) δ (ppm) ： 10.75 (s? 1H)，9·07 (s，1H)，8.92 (d，1H)，8·39 (dd，2H)，7·80-7·65 (m， 4H)，7.46 (s，1H)，4·34 (t，2H)，3·36-2·93 (m，6H)，2.81 (d， 3H)，2.61 (s，3H)，2xCH2訊號受到H20訊號遮蔽。 實施例1145_氣-2,3_二氩-1-[5·(5_甲基噚唑-2_基)萘小基胺基羰基】-6_ (4-甲基六氩吼喷-1-基)-111_弓1鳴 使用實施例4之類似方式，自5-U，3-二氳-6-(4-甲基六 氫口比畊-1-基)-1Η-吲哚（D13)和5-(5-甲基崎嗤-2-基)萘讎 1-基胺（D114)製備標題化合物。將標題化合物轉換成其 鹽酸鹽淺黃色粉末（41%)。 iNMR (HC1 鹽）（250MHz，d6DMSO) δ (ppm) : 10.94 (s， 1H)，9·16 (d，1H)，8·96 (s，1H)，8·18 (dd，2H)，7·75 (s，1H)， 7.70-7.59 (m，3H)，7·30 (s，1H)，7.16 (s，1H)，4.34 (t，2H)， 127 尺度適用中國國家標準（CNS ) A4規格（210X297公釐) (請先閱讀背面之注意事項再IPIb本頁) 裝· 訂- 線 509687 A7 ____— —_B7 五、發明説明（126 ) 3.47 (t，2H) ’ 3.37-2.95 (m，8H)，2·78 (d，3H)，CH3訊號受 到DMSO訊號遮蔽。 實施例115 2,3_二氩-5-甲氧基-l_【s_(5-甲基_唑-2_基)萘_1_基胺基羰 基]-6_(4_甲基六氫吡啡_ι_基)_ih_h5I哚 使用實施例4之類似方式，自2,3_二氫甲氧基冬甲 基六氫°比°井-1-基HH_吲哚（WO 95706627中間物3)和 5_(5_曱基畤唑-2-基)萘小基胺（D114)製備標題化合物， 獲得鹽酸鹽淺黃色粉末（56%)。^ iHNMR (HC1 鹽）（250MHz，d6DMSO)S (ppm) : 10.95(s， 1H)，9·14 (d，1H)，8·79 (s，1H)，8.17 (dd，2H)，7.69-7.58 (m， 4H)，7·17 (s，1H)，6·94 (s，1H)，4.29 (t，2H)，3·77 (s，3H)， 3.38 (m，4H)，3.16 (m，4H)，2.95 (t5 2H)，2·77 (d，3H)，2.51 (s5 3H) 〇 實施例116 5_淡-2,3-二氩-1·[3-甲基-4-(續咬-2-基)苯基胺基援基】-6-(4-甲基六氩吡基)_m_吲嗦 使用實施\例4之類似方式，自3-甲基-4-(嘧啶-2-基)苯胺 (D115)和 5-&gt;臭-2,3-二氮-6-(4-甲基六氮口比11 井-1-基)-1Η-吲哚（D15)製備得米黃色泡沫標題化合物（34%)。將 此泡沫自丙酮中轉換成其鹽酸鹽黃色固體。 iNMR (HC1 鹽）（250MHz，d6DMSO)S(ppm) : 10.50(br s，1H)，8·90 (d，2H)，8·75 (s，1H)，7·84 (m，2H)，7·60 (m， 2Η)，7·43 (m，2Η)，4·20 (t，2Η)，3·54 (d，1Η)，3·33 (d，1Η)， 128 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐〉 -----------^-- (請先閲讀背面之注意事項再β本頁) 訂 經濟部智慧財產局8(工消費合作社印製 509687 A7 ______B7 五、發明説明（127) 3·10 (m，6H)，2·85 (d，3H)，2·54 (s，3H)。 實施例117 2,3_二氩_5_甲氧基-Ι-p-甲基_4_(嘴咬基)苯基胺基叛 基Η·(4_甲基六氩吡+1-基)-1Η_吲哚 使用實施例4之類似方式，自3_甲基_4_(嘧啶_2_基)苯胺 (D115)和2,3-一風r5-甲氧基-6-(4-甲基六氫吼啡心-基)_ III·-引哚（WO 95/06627中間物3)製備得米黃色泡^標 題化合物（32%)。將此泡沫自丙酮中轉換成其鹽酸鹽黃 棕色固體。 、--、 WMR (HC1 鹽）（250MHz，d6DMSO)S(ppm) ·· 10.45(br s，1H)，8·90 (d，2H)，8·59 (s，1Η)，7·83 (d，1H)，7.67 (s，1Η)， 7.60(m，2H) ’ 7.40 (t，1H)，6.92 (s，1·Η)，4·15(ί，2Η)，3.77 (s，3H)，3.45 (m，4H)，3·17 (m，4H)，2·96 (t，2H)，2.82 (d， 3H)，2·54 (s，3H)。 實施例118 5-氯_2,3-二氫_6-(4_甲基六氩吡畊-1_基)-l-[3-甲基_4-(嘧啶 -基)苯基胺基叛基】-1H-,鳴 使用實施例4之類似方法，自3-甲基-4-(嘧啶-2-基)苯胺 (D115)和5-氣-2,3_二氫-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚（D13)製備得米黃色泡沫標題化合物（47%)。將 此泡沫自丙酮中轉換成其鹽酸鹽黃色固體。 i NMR ( HC1 鹽）（250MHz，d6DMSO) δ (ppm) : 10.50 (br s，1Η)，8.90 (d，2H)，8.71 (s，1Η)，7·84 (d，1H)，7.82 (s，1H)， 7.60 (m，2H)，7·41 (t，1H)，7.29 (s，1H)，4.20 (t，2H)，3.53 129 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） (請先閲讀背面之注意事項再本頁) 裝· 經濟部智慧財產局員工消費合作社印製 509687(Please read the precautions on the back first, then this page) Installation and wiring _ B7 V. Description of the invention (117) 5_ 气 _2,3_ 二 argon_6_ (4_methylhexapyridine small base) + [ 4- (pyridine: yl) phenylphenyl carbonyl] -1Η-indole Using a similar method to that described in note 1, the title compound prepared from 4- (σbigonyl) benzoic acid (ό103) was used to form an isocyanate. 5_gas_2, hydrazone di 6- (4-methylhexahydropyridine small group) _11 {earthworm indole (D13) was added to obtain light yellow solid urea (30%). HNMR (250MHz, CDC13) δ (ppm): 9.01 (s, 1H), 8.61 (s, 1Η), 8.47 (d, 1Η), 8.02 (d, 2Η), 7.83 ( s, 1Η), 7.61 (d, 2Η), 7.16 (s, 1H) '6.55 (s, 1H), 4.13 (t5 2H), 3.20 (t, 2H), 3.11 (br s, 4H), 2.61 (br s, 4H), 2.36 (s, 3H). Example 96 5-Bromo_2,3_diargon-6_ (4-methylhexapyridinyl) small [4 (pyridin-2-yl) phenylaminocarbonyl 1-1H_indole Instructions for use 1 Similarly, isocyanate was formed from the title compound prepared from 4-decaline-3-yl) benzoic acid (D103), and then bromide-2,3-dihydro6- (4-methylhexahydropyridine) was formed. ) -Indole (D15) was added to obtain yellow solid urea (30%). ^ 'H NMR (250MHz, CDC13) δ (ppm): 9.00 (s5 1H) ^ 8.6 (s printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 1H)' 8.48 (d, 1H), 8.01 (d, 2H), 7.83 (s, 1H), 7.61 (d, 2H), '7.34 (s, 1H), 6.57 (s, 1H), 4.13 (t, 2H), 3.20 (t, 2H), 3 10 (br s, 4H), 2.62 (br s, 4H), 2.36 (s, 3H). Example 97 S-Ga_2,3_diargon-6- (4-methylhexafluoropyridine + yl) small [(2 · phenylpyridinyl) aminocarbonylHH-indole ^ 119 Paper size applies to Chinese national standard ((: Called 8th secret (21〇 ^ 297 mm) 509687 A7 B7 V. Description of the invention (118) A similar method to the use of 1 is prepared from 6-phenylnicotinic acid (D104) The title compound was formed as an isocyanate, followed by the addition of 5_chloro_2,3_dihydro-6- (4-methylhexahydropyridine) -1Η_indole (D13) to obtain a white solid urea (48%) ! HNMR (250MHz, d6DMSO) δ (ppm): 8.87 (dd, 2Η), 8 l2 (m, 3H), 7.96 (d, 1H), 7.83 (s51H), 7.47 (m, 3H), 7 · 28 (s 1H) ', 4.22 (t, 2H)' 3.17 (t, 2H), 2.95 (br s, 4H), 2.54 (br s is masked by DMSO peak, 4H), 2.26 ( s, 3H). Example 98 S-Meta-2,3-diargon-6- (4-methylhexapyridine + i-yl) small [(2-phenylpyridinyl) aminocarbonylHH _Indole ~ Using a method similar to Note 1, the isocyanate was formed from the title compound prepared from 6-phenylnicotinic acid (D104), and then 5-bromo_2,3_dihydro_6_ (4_methylhexa Hydrogenation-1_yl) -1 Qindole (D15) was added to obtain Pure white solid urea (46%). · Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs! H NMR (250MHz, d6DMSO) δ (ppm): 8.86 (dd, 2Η) ^ 8.12 (m5 3H), 8.09 (d, 1H), 7.83 (s, 1H), 7.47 (m, 4H), 4.22 (t, 2H), 3.18 (t, 2H), 2.94 (br s5 4H), 2.53 ( br s, masked by the DMSO peak, 4H), 2.26 (s, 3H). Example 99 5-Gas_2,3-Digas + Heptamethyldiphenyl) phenylaminocarbonyl] Hexafluoropyridin-1-yl) -1Η-pyridine Using a similar method to that described in note 1, the title compound was prepared from 4_ (6_fluoridyl_3_yl) benzoic acid (D105) to form an isocyanate. Krypton 120 509687 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Description of the invention (119) -2,3-diaza-6- (4-methylhexanitrogen σ ratio 11 Well-1-based (D13 ) Added to obtain beige solid urea (23%). LH NMR (250MHz, CDC13) δ (ppm): 8.03 (d5 2H) ^ 7.83 (s? 1H), 7.35 (d, 1H), 7.14 (s, 1H) , 6.59 (s, 1H), 4.11 (t, 2H), 3.18 (t, 2H), 3.11 (brs, 4H), 2.74 (s, 3H), 2.60 (brs, 4H), 2.36 (s, 3H). Example 1005_A_2,3_diaza-l- [4- (6-methyl tower flavor_3_yl) phenylamino peptidyl group] _6- (4_methylhexahydropyridine) -1Η_ 弓 丨 Dodine Using a similar method to that described in note 1, the title compound prepared from 4- (6 · pyridyl-3-yl) benzoic acid (D105) forms an isocyanate, followed by 5-bromo-2,3 -Dihydro-6- (4-methylhexahydropyridine 4--1-yl) _1H-indole (D15) was added to obtain beige solid urea (28%). 4 NMR (250MHz, CDC13) δ (ppm): 8.05 (d, 2H), 7.84 (s, 1H), 7.72 (d, 1H), 7.60 (d, 2H), 7.35 (m, 2H), 6.57 (s, 1H), 4.13 (t, 2H), 3.20 (t, 2H), 3.10 (br s, 4H), 2.75 (s, 3H), 2.62 (br s, 4H), 2.36 (s, 3H ). Example 1015-Gas-2,3-Diargon-6- (4-methylhexaargyryl) -l- [4- (pyridin-3-yl) phenylaminocarbonyl] -1A-indole use Description 2 in a similar way 'from 5-Gas-2,3-diazol-1- (4-erphenylaminocarbonyl) -6- (4-methylhexahydropyridyl) -1Η-indole (D43) and 3-pyridineboronic acid (Bulletin of Chemical Physics, 1983, 31 (12), 4573) to prepare the title compound to obtain a light cream-colored powder (19%). 121 (Please read the precautions on the back before this page). Installation ·-! ·% &Gt; Line _ This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 509687 A7 B7-1 V. Invention Explanation (120)! HNMR (250MHz, d6DMSO) δ (ppm): 8.81 (s, 1H) ^ 8.61 (s5 1H), 8.45 (d, 1H), 7.96 (d, 1H), 7.7 〇, 1H) , 7.62 (m, 4H) '7.14 (s, 1H), 4.08 (t, 2H), 3.04 (t, 2H), 2.83 (brs, 4H), 2.15 (s, 3H). 2xCHJfl is obscured by the DMSO signal. Example 102 5-Chloro-2,3-diargon_1_ [4_ (5 · methylpyridin_2-yl) phenylaminosulfonylpyridinium_ (4-methylhexapyridin-1-yl)- 1Η_indole Using a method similar to that in Example 4, from 5-Gas-2,3-dihydro-6- (4-methylhexahydroport than Kojito (D13) and 4- (5-methyl 1Satyl) present amine (D107) to prepare the title compound to obtain a light cream-colored powder (63%). NMR (250MHz, d6DMSO) δ (ppm): 8.78 (s, 1Η), 7.72 (m, 5H), 7.20 (s51H), 6.90 (s, 1H), 4.14 (t, 2H), 3.08 (t, 2H), 2.96 (br s, 4H), 2.72 (brs, 4H), 2.38 (s, 3H), 2.33 (s, 3H). Example 103 2,3-Dihydro-5 · methoxy-1- [4- (5-methylfluoren-2-yl) phenylaminocarbonyl]- 6- (4-methylhexapyridin-1-yl) -1Η-cylindole Using a similar method to that described in Example 4, from 2,3-dihydro-5- 曱 oxy · 6 · (4- 曱Hexahydropyridine) -1Η-indole (WO 95/06627 intermediate 3) and 4- (5-methyloxazol-2-yl) aniline (D107) to prepare the title compound to obtain a light cream-colored powder (44%). LH NMR (250MHz, d6DMSO) δ (ppm): 8.80 (s, 1H) ^ 7.97 (d5 2H), 7.86 (d, 2H), 7.77 (s, 1H), 7. · 08 (s, 1H) 7.00 (s, 1H), 4.27 (t, 2H), 3.89 (s, 3H), 3.25 (t, 2H), 3.07 (br s, 4H), 2.61 (br s, 7H), 2.52 (s, 3H), 2.37 (s, 3H). 122 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) --------- _ equipment ^ _ I (Please Please read the notes on the back first and then this page) Printed and printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (121 Printed by the Employees’ Cooperative of the Intellectual Property Bureau of the Ministry of Economy -1_ [4- (5-Methylsulfonyl-2-yl) phenylaminocarbonyl] -6-methylhexahexan-1-yl) _imming, using a similar method as in Example 4, since 5 _Bromo_2,3_dihydro (wastelyl hexahydrocae-1_yl) -1Η-indole (DI5) and 4_ (5_fluorenyloxazolyldongyl) aniline i (D107) to prepare the title compound To obtain a light cream-colored powder (23%). H NMR (250MHz, CDC13) δ (ppm): 7.94 (d, 2H), 7.82 (s, 1Η) '7.52 (d, 2Η)' 7 · 33 (s, 1Η), 6.81 (s, 1Η), 6.58 (d, 1Η), 4.11 (t, 2H), 3.15 (m, 6H), 2.69 (br s, 4H), 2.42 (s, 3H ), 2.39 (s, 3H). Example 105 s-gas-2,3-dihydro small [4-Mesylpyrazole_4yl) phenylaminocarbonyl] _6 (4_methylhexapyridinyl) _1H-indomin Instructions for use 1 In a similar method, the title compound prepared from 4-methyl-methyl-xanthyl) benzoic acid (WCW / 43% 2) forms an isocyanate motif, and then 5-gas dihydro-6 '(4-methylhexa Hydrogenated small base) _m_ind. Do / D13) was added to obtain pure white solid urea (18%). H NMR (250MHz, CDC13) δ (ppm &gt;: 7 82 (s, 1H), 7 s 1H), 7.55 (s, 1H), 7.41 (s, 4H), 7 13 (s, m), 6 44 &amp; ih), 4.07 (t, 2H), 3.93 (S, 3H), 3.16 (t5 2H), 3.1 () (br s, 4H), 2 6 ( br s, 4H), 2.35 (s, 3H). Example 106 &amp; Ao-2,3-digas-1 * (1-methyl material ice-based) phenylamino quinyl group] Final methyl six-gas ton spray-1_ group 丨 Ming 123 Financial Accountant (CNS) Α4 · (210X297 Gong Chuding (please read the precautions on the back first and then the page)), 1T line 509687 A7 B7 Printed by the Consumers ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs ) Using a method similar to Note 1, the title compound prepared from 4- (1-fluorenylpyrazol-4-yl) benzoic acid (W097 / 43262) forms an isocyanate, and then 5-bromo-2,3-dihydro- 6- (4-methylhexahydropyridin-1-yl) -1) -indole (D15) was added to obtain beige solid urea (30%).! H NMR (250MHz, CDC13) δ (ppm): 7.83 ( s, 1H), 7.71 (s, 1H), 7.54 (s, 1H), 7.40 (s, 4H), 7.31 (s, 1H), 6.46 (s, 1H), 4.05 (t, 2H), 3.93 (s, 3H), 3.15 (t, 2H), 3.08 (br s5 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 107 5-fluorocyanomethyl Phenyl-4-ylaminocarbonyl] -2,3_diargon-6- (4-methylhexapyridinyl) -1Η-indole Using a method similar to that in Note 1, from 4- (4- Cyanomethylmethylbenzyl) phenylarsinic acid (D1 06) The prepared title compound forms an isocyanate, and then 5-chloro-2,3-diazine-6_ (4-methylhexazine-0-well-1-yldo (D13)) is added to obtain light yellow solid urea (39 %). 4 NMR (250MHz, CDC13) δ (ppm): 7.82 (s, 1H), 7.64 (d, 1H), 7.44-7.55 (m, 6H), 7.15 (s, 1Η), 6.52 (s , 1Η), 4.11 (t, 2H), 3.19 (t, 2H), 3.10 (brs, 4H), 2.60 (brs, 4H), 2.35 (s, 3H). Example 108 5-Bromocyano- 3f_methylbiphenyl-4-ylaminocarbonyl group] _2,3-diargon-6- (4-methylhexapyridin-1-yl) -1Η-indole Use a similar method as described in Note 1, From the title compound prepared from 4- (4-cyano-3-methylphenyl) phenylarsinic acid (D106), an isocyanate was formed, and then 5-bromo 124 was prepared. Please read the precautions on the back before mb this page) Order-line paper size applies Chinese National Standard (CNS) A4 specification (21 × 297 mm) 509687 A7 B7 V. Description of the invention (123 -2,3-dihydro -6- (4-methylhexahydropyrimidinyl)] h-indole (D15) was added to obtain urea (28%) as a pale yellow solid. H NMR (250MHz, CDC13) δ (ppm): 7.83 (s, 1H), 7.64 (d, 1H), 7.42-7.55 (η, 6Η), 7.33 (s, 1H), 6.54 (s, 1H), 4.10 (t, 2H) '3.18 (t, 2H), 3.08 (brs, 4H), 2.60 (brs, 4H), 2.35 (s, 3H) 〇 Example 109 5- 气 _2,3_ 二Argon [4_ (2_methylpyridinium_5_yl) phenylaminocarbonyl] -6 · (4-methylhexapyridin_1_yl) _1Η_indole Use a similar method as described in Note 1, An isocyanate was formed from the title compound prepared from 4- (2, fluorenylpyridin-5-yl) benzoic acid (WO 97/43262), and then 5-chloro-2,3-dihydro-6- (4-methylhexan Hydrogen σ-biffinyl group) was added to obtain a beige solid urea (2%). H NMR (250MHz, CDC13) δ (ppm): 8.68 (d, 1H), 7 82 (s 6.50 (s, 1H). 4.11 (t, 2H) &gt; 3.18 (t, 2H), 3.11 (br s, 4H) &gt; 2.59 (br s, 7H), 2.36 (s5 3H). Example 110 Printed 5-Ket-2,3-Dimethyl-Hydroxy-5 by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs _Yl) Phenylamino group] o-Methylhexazine-1. Kei mouth uses a similar method, since the end of the base is 5-base) Benzoic acid = 097/4 times) title The compound formed isocyanate, and -mo-2,3-dihydro-o-methylhexahydrocaffeine (D15) was added to obtain beige solid urea (10%). 125 This paper size applies Chinese National Standard (CNS) A4 specification f21〇X29 $ Jy 509687 Printed by the Consumer Cooperatives of Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (124 4 NMR (250MHz, d6DMS0) δ (ppm): 8 79 ( d, 1H), &amp; 1H), 7.99 (dd, 1H), 7.84 (s, ιΗ), 7 71 (q, 4H), 7 43 (s, 1Ή), '7.36 (d, 1H), 4.21 (t, 2H), 3el7 (t, 2H), 2.96 (br s, 4H), 2.54 (brs, masked by the DMSO peak, 7H), 2 31 (S, 3H). Example 111 5-Gas-Gong-Hydroxy-methylidene is read from the bases of oxadiazole + acrosyl group] -6- (4-methylhexakid roared in a similar manner as in Example 4, Since 5-Gas-2,3-dihydro-6- (4-methylhexahydropyridine (D13) and 5- (3-methyl · 1,2,4 dimethyl di-2-yl) Naphthylamine (Dill) to prepare the title compound. The title compound was converted to its hydrochloride pale yellow powder (59%). INMR (HC1 salt) (250MHz, d6DMSO "(ppm): ΐ〇 · 82 (δ 1H) , 9.03 (s, 1Η), 8.92 (d, 1H), 8.42 (m, 2H), 7.78-7.65 (m 4H), 7.31 (s, 1H), 4.34 (t, 2H ), 3.48-2.94 (m, 10H), 2.80 (d 3H), 2.54 (s, 3H). 'Example 112 2,3 _ «— Ga-5-methylamino-l- [5- (3_methyl -1,2,4_present diolyl group) tea_1-aminoaminocarbonyl group] _6_ (4-methylhexapyridin-1-yl) _1H_indole Using a similar manner as in Example 4, since 2, 3-dihydro-5-methoxy-6- (4-methylhexahydropyridine) -1H-indole (WO 95/06627 intermediate 3) and 5- (3-methyl-1,2 , 4-4 diazol-5-yl) naphthylamine (Dill) to prepare the title compound. The title compound was converted to its hydrochloride colorless powder (68%). 4 NMR ( HC1 salt) (250MHz, d6DMSO) δ (ppm): 10.87 (s, 1H), 8.92 (s, 1H), 8.87 (d, 1H), 8.41-8.33 (m, 2H), 7.78 sides 126 sheets The dimensions are applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm). (Please read the precautions on the back first | 1 | ^ this page}. Installation ·-Thread 509687 A7 ____B7 V. Description of the invention (125) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 7.65 (m, 3H), 7.60 (s, 1H), 6.94 (s51H), 4.30 (t, 2H), 3.77 (s, 3H), 3.40 (m, 4H), 3.20 (m, 4H), 2.89 (t, 2H), 2.75 (d, 3H), 2.53 (s, 3H). Argon-1_ [5- (3-methyldiazol-5-yl) naphthalen-1-ylaminoalkyl] -6- (4-methylhexazol-4-yl) -1Η- 嗦In a similar manner to 4, from 5-bromo_2,3_dihydro-6- (4-fluorenylhexahydropyridin-1-yl) -1H-indole (D15) and 5- (3methyl-1 , 2,4-Pyridene-5-yl) naphthalene-1 -ylamine (Dili) to prepare the title compound. The title compound was converted into its hydrochloride pale beige powder (36%). lHNMR (HCm) (250MHz, d6DMSO) δ (ppm): 10.75 (s? 1H), 9.07 (s, 1H), 8.92 (d, 1H), 8.39 (dd, 2H), 7.80- 7.65 (m, 4H), 7.46 (s, 1H), 4.34 (t, 2H), 3.36-2.93 (m, 6H), 2.81 (d, 3H), 2.61 (s, 3H ), The 2xCH2 signal is obscured by the H20 signal. Example 1145_Gas-2,3_Diargon-1- [5 · (5_methyloxazole-2_yl) naphthylaminocarbonylcarbonyl] -6_ (4-methylhexaargin-1 -Yl) -111_Gong Yiming Using a similar method as in Example 4, from 5-U, 3-difluorene-6- (4-methylhexahydropyridin-1-yl) -1fluorene-indole ( D13) and 5- (5-methylaziridin-2-yl) naphthacene-1-ylamine (D114) to prepare the title compound. The title compound was converted into its hydrochloride pale yellow powder (41%). iNMR (HC1 salt) (250MHz, d6DMSO) δ (ppm): 10.94 (s, 1H), 9.16 (d, 1H), 8.96 (s, 1H), 8.18 (dd, 2H), 7 · 75 (s, 1H), 7.70-7.59 (m, 3H), 7.30 (s, 1H), 7.16 (s, 1H), 4.34 (t, 2H), 127 scales apply Chinese National Standard (CNS) A4 Specifications (210X297 mm) (Please read the precautions on the back before IPIb page) Binding · Binding-Line 509687 A7 ____ — —_B7 V. Description of the invention (126) 3.47 (t, 2H) '3.37-2.95 (m, 8H), 2.78 (d, 3H), CH3 signal is masked by DMSO signal. Example 115 2,3_Diargon-5-methoxy-l_ [s_ (5-methyl_azole-2_yl) naphthalene_1_ylaminocarbonyl] -6_ (4-methylhexahydropyridine Brine_ι_yl) _ih_h5I indole is used in a similar manner as in Example 4, starting from 2,3_dihydromethoxytolylmethylhexahydro ° ratio-1-Hylindole (WO 95706627 Intermediate 3) The title compound was prepared with 5- (5-fluorenyloxazol-2-yl) naphthylamine (D114) to obtain the hydrochloride as a pale yellow powder (56%). ^ iHNMR (HC1 salt) (250MHz, d6DMSO) S (ppm): 10.95 (s, 1H), 9.14 (d, 1H), 8.79 (s, 1H), 8.17 (dd, 2H), 7.69- 7.58 (m, 4H), 7.17 (s, 1H), 6.94 (s, 1H), 4.29 (t, 2H), 3.77 (s, 3H), 3.38 (m, 4H), 3.16 ( m, 4H), 2.95 (t5 2H), 2.77 (d, 3H), 2.51 (s5 3H). Example 116 5_Meta-2,3-diargon-1 · [3-methyl-4- (Continuous bite-2-yl) phenylamino group] -6- (4-methylhexapyridyl) _m_indole Using a similar manner as in Example 4, from 3-methyl-4- ( Pyrimidin-2-yl) aniline (D115) and 5- &gt; Sm-2,3-diaza-6- (4-methylhexazine port ratio 11 well-1-yl) -1H-indole (D15) The title compound (34%) was obtained as a beige foam. This foam was converted from acetone to its hydrochloride yellow solid. iNMR (HC1 salt) (250MHz, d6DMSO) S (ppm): 10.50 (br s, 1H), 8.90 (d, 2H), 8.75 (s, 1H), 7.84 (m, 2H), 7.60 (m, 2Η), 7.43 (m, 2Η), 4.20 (t, 2Η), 3.54 (d, 1Η), 3.33 (d, 1Η), 128 paper sizes applicable China National Standard (CNS) A4 specification (210X297 mm) ----------- ^-(Please read the notes on the back before β page) Order the Intellectual Property Bureau of the Ministry of Economic Affairs 8 (industrial consumption Printed by the cooperative 509687 A7 ______B7 V. Description of the invention (127) 3.10 (m, 6H), 2.85 (d, 3H), 2.54 (s, 3H). Example 117 2,3_Diargon_ 5-Methoxy-l-p-methyl_4_ (mouth-bitenyl) phenylaminostilbene ((4-methylhexapyridine + 1-yl) -1Η_indole Using Example 4 In a similar manner, from 3-methyl_4_ (pyrimidin_2_yl) aniline (D115) and 2,3-yifeng r5-methoxy-6- (4-methylhexahydroxin-yl)- III · -Indole (WO 95/06627 Intermediate 3) was prepared as a beige foam ^ the title compound (32%). This foam was converted from acetone to its hydrochloride yellow-brown solid.,-, WMR (HC1 Salt) (250MHz, d6DMSO) S (ppm) ·· 10.45 (br s, 1H), 8.90 (d, 2H), 8 · 5 9 (s, 1Η), 7.83 (d, 1H), 7.67 (s, 1Η), 7.60 (m, 2H) '7.40 (t, 1H), 6.92 (s, 1 · Η), 4.15 ( ί, 2Η), 3.77 (s, 3H), 3.45 (m, 4H), 3.17 (m, 4H), 2.96 (t, 2H), 2.82 (d, 3H), 2.54 (s, 3H). Example 118 5-Chloro-2,3-dihydro-6- (4-methylhexapyridine-1_yl) -l- [3-methyl_4- (pyrimidin-yl) benzene Aminoamino group] -1H-, Ming uses a similar method as in Example 4 from 3-methyl-4- (pyrimidin-2-yl) aniline (D115) and 5-Ga-2,3-dihydro- 6- (4-methylhexahydropyridin-1-yl) -1Η-indole (D13) was prepared to give the title compound (47%) as a beige foam. This foam was converted from acetone to its hydrochloride yellow solid I NMR (HC1 salt) (250MHz, d6DMSO) δ (ppm): 10.50 (br s, 1Η), 8.90 (d, 2H), 8.71 (s, 1Η), 7.84 (d, 1H), 7.82 ( s, 1H), 7.60 (m, 2H), 7.41 (t, 1H), 7.29 (s, 1H), 4.20 (t, 2H), 3.53 129 This paper standard is applicable to China National Standard (CNS) A4 specifications ( 210 X 297 mm) (Please read the precautions on the back first, and then this page)

(d，1H) ’ 3·37 (d，2H)，3·14 (m，6H)，2·86 (d，3H)，2·54 (s， 3H)。 實施例119 5_溴-2,3-二氣-l_【3_甲基_4(射_5基)苯基胺基叛基】+ (‘甲基六氩咄牛1-基卜瓜喷鳴 使用貫施例4之類似方法，自3_甲基冰(哺唆_5_基)苯胺 (D116)和5_溴_2,3_二氫各(4甲基六氫吡畊基) ih_ ’朵（D15)製備得泡沫標題化合物（82%)。將此泡沫 自丙酮中轉換成其鹽酸鹽純白色固體。 H NMR ( HC1 鹽）（25〇MHz，d6DMSO) δ (ppm) : 1〇·65 (br s，1Η) ’ 9·18 (s，1Η)，8·86 (s，2Η)，8·73 (s，1Η)，7·82 (s51Η)， 7·62 (s，1H)，7.55 (dd，1H)，7·45 (s，1H)，7·25 (d，1H)，4·19 (t，2H)，3·54-2·98 (m，10H)，2·85 (d，3H)，2·28 (s，3H)。 實施例120 5-氣_2,3-二氩-1-[3-甲基-4-(續咬基)苯基按基幾基卜6_ (4_甲基六氩吡畊-1-基)_ih_吲哚 使用實施例4之類似方法，自3-甲基-4-(嘧啶_5_基)苯胺 (D116)和5_氣_2,3_二氫-6_(4-甲基六氫吡畊 吲唏（D13)製備得泡沫標題化合物（84%)。將此泡沫 自丙酮中轉換成其鹽酸鹽純白色囡韓。 i NMR ( HC1 鹽）（250MHz，d6DMSO) δ (ppm) : 1〇 67 (br s，1H)，9·18 (s，1H)，8·86 (s，2H)，8·73 (s51H)，7.82 (s，1H)， 7.58 (s，1H)，7·55 (dd5 1H)，7·27 (m，2H)，4.19 (t，2H)， 3.53-3.00 (m，10H)，2·84 (d，3H)，2.28 (s，3H) 〇 130 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐T '^^ (請先閲讀背面之注意事項本頁) .裝· 訂 經濟部智慧財產局員工消費合作社印製 509687 A7 B7 經濟部智慧財產局員工消費合作社印製 五、發明説明（129) 實施例1212,3-二氩-5-甲氧基_1-[3_甲基-4-(嘧啶_5_基)苯基胺基羰 基】_6-(4-甲基六氩吡命_1_基)-1Η_啼哚 使用實施例4之類似方式，自3-甲基-4-(嘧啶-5-基)苯胺 (D116)和2,3-二氫-5-曱氧基-6-(4-甲基六氫吡畊-1-基)-1H-吲哚（W0 95/06627中間物3),製備得泡沫標題化合 物（97%)。將此泡沫自丙酮中轉換成其鹽酸鹽純白色固 體。 4 NMR ( HC1 鹽）（250MHz，d6DMSO) δ (ppm) : 10.74 (br s，1H)，9· 18 (s，1H)，8.88 (s，2H)，8·59 (s，1Η)，7.60 (m，3H)， 7.22 (d51H)，6·92 (s，1H)，4·15 (t，2H)，3.77 (s，3H)，3.45 (m，4H)，3·10 (m，4H)，2.98 (t，2H)，2.81 (d，3H)，2.28 (s， 3H) 〇 實施例1225·溴_2,3-二氩-1_[4-(2,6·二甲基吡啶_4-基)各甲基苯基胺 基羰基】_6·(4-甲基六氩吡畊-1-基)-1Η·吲嗦 使用實施例4之類似方法，自4-(2,6-二甲基吡啶-4-基)-3-甲基苯胺（D88)和5-溴-2,3-二氫冬(4-甲基六氫吡畊-1-基)_1H-吲哚（D15)製備得淺黃色泡沫標題化合物 (89%)。將其自丙酮中轉換成鹽酸鹽淺黃色固體。 NMR(自由鹼）(250MHz，CDC13) δ (ppm) ·· 7.83 (s，1H)， 7.38-7.27 (m，3Η)，7· 14 (d51Η)，6·90 (s，2Η)，6.47 (s，1Η)， 4·11 (t，2H)，3.19 (t，2H)，3.08 (br m，4H)，2·60 (br m，4H)， 2.56 (s，6H)，2·35 (s，3H)，2·27 (s，3.H)。 131 (請先閱讀背面之注意事項 本頁) •裝·(d, 1H) '3.37 (d, 2H), 3.14 (m, 6H), 2.86 (d, 3H), 2.54 (s, 3H). Example 119 5-Bromo-2,3-digas-l_ [3-methyl-4 (radio-5) phenylaminomethyl] + ('methylhexagonal Ming uses a similar method as described in Example 4 from 3-methyl ice (five-5-yl) aniline (D116) and 5-bromo-2,3-dihydrogen (4 methylhexahydropyridyl) ih_ 'Duo (D15) prepared the title compound of foam (82%). This foam was converted from acetone to its hydrochloride pure white solid. H NMR (HC1 salt) (25MHz, d6DMSO) δ (ppm): 10.65 (br s, 1Η) '9.18 (s, 1Η), 8.86 (s, 2Η), 8.73 (s, 1Η), 7.82 (s51Η), 7.62 (s , 1H), 7.55 (dd, 1H), 7.45 (s, 1H), 7.25 (d, 1H), 4.19 (t, 2H), 3.54-2 · 98 (m, 10H) , 2.85 (d, 3H), 2.28 (s, 3H). Example 120 5-Gas_2,3-diargon-1- [3-methyl-4- (continyl) phenyl According to the same method as in Example 4 using 6- (4-methylhexapyridin-1-yl) _ih_indole as a base, from 3-methyl-4- (pyrimidin-5-yl) aniline (D116 ) And 5_gas_2,3_dihydro-6_ (4-methylhexahydropyridine indium (D13)) to prepare the title compound (84%) as a foam. This foam was converted from acetone to its hydrochloride salt pure white Han. I NMR (HC1 salt) (250MHz, d6DMSO) δ (ppm): 1067 (br s, 1H), 9 · 18 (s, 1H), 8.86 (s, 2H), 8.73 ( s51H), 7.82 (s, 1H), 7.58 (s, 1H), 7.55 (dd5 1H), 7.27 (m, 2H), 4.19 (t, 2H), 3.53-3.00 (m, 10H), 2.84 (d, 3H), 2.28 (s, 3H) 〇130 This paper size is applicable to China National Standard (CNS) A4 specifications (210X297 mm T '^^ (Please read the precautions on the back page first). · Order printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Printed Description of the Invention (129) Example 1212,3-Diargon-5-methoxy-1-_1- [ 3-methyl-4- (pyrimidin_5_yl) phenylaminocarbonyl] -6- (4-methylhexapyridin_1-yl) -1pyridine In a similar manner as in Example 4, since 3-methyl-4- (pyrimidin-5-yl) aniline (D116) and 2,3-dihydro-5-fluorenyloxy-6- (4-methylhexahydropyridin-1-yl) -1H -Indole (WO 95/06627 intermediate 3) to prepare the title compound as a foam (97%). This foam was converted from acetone to its hydrochloride pure white solid. 4 NMR (HC1 salt) (250MHz, d6DMSO) δ (ppm): 10.74 (br s, 1H), 9.18 (s, 1H), 8.88 (s, 2H), 8.59 (s, 1Η), 7.60 (m, 3H), 7.22 (d51H), 6.92 (s, 1H), 4.15 (t, 2H), 3.77 (s, 3H), 3.45 (m, 4H), 3.10 (m, 4H ), 2.98 (t, 2H), 2.81 (d, 3H), 2.28 (s, 3H). Example 1225 · bromo_2,3-diargon-1_ [4- (2,6 · dimethylpyridine_ 4-yl) each methylphenylaminocarbonyl group] -6 · (4-methylhexapyridin-1-yl) -1Η · indole Using a method similar to that in Example 4, starting from 4- (2,6- Dimethylpyridin-4-yl) -3-methylaniline (D88) and 5-bromo-2,3-dihydrodong (4-methylhexahydropyridin-1-yl) _1H-indole (D15 ) The title compound (89%) was prepared as a light yellow foam. It was converted from acetone to the hydrochloride salt as a pale yellow solid. NMR (free base) (250MHz, CDC13) δ (ppm) 7.83 (s, 1H), 7.38-7.27 (m, 3Η), 7.14 (d51Η), 6.90 (s, 2Η), 6.47 ( s, 1Η), 4.11 (t, 2H), 3.19 (t, 2H), 3.08 (br m, 4H), 2.60 (br m, 4H), 2.56 (s, 6H), 2.35 ( s, 3H), 2.27 (s, 3.H). 131 (Please read the precautions on this page first)

、1T 線 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐) 509687 A7 B7 五、發明説明（130) 實施例123 2,3·二氩-5-甲氧基小[4-(2,6-二甲基吡啶_4_基)-3-甲基苯 基胺基羰基]冬(4·甲基六氩吡畊-1-基)-1Η-吲哚 使用實施例4之類似方法，自4-(2,6-二甲基吡啶-4-基)-3-曱基苯胺（D88 )和2,3-二氫-5-曱氧基-6-(4-甲基六氫吡畊 -1·基)-1Η-吲哚（WO95/06627中間物3)製備得淺黃色泡 沫標題化合物（95%)。將其自丙酮中轉換成鹽酸鹽黃色 固體。 4NMR(自由鹼）(250MHz，CDC13) δ (ppm): 7.70 (s，1H)， 7.37 (d，1H)，7.30 (dd，1H)，7·14 (d，1Η)，6·90 (s，2H)，6·73 (s，1H)，6.42 (s，1H)，4·09 (t，2H)，3.84 (s，3H)，3·20 (t，2H)， 3.12 (br s，4H)，2.61 (br s，4H)，2.56 (s，6H)，2.34 (s，3H)， 2·27 (s5 3H) 〇 實施例124 5-氯_2,3-二氩_l_[5-(2,6-二甲基吡啶_4_基)萘-1·基胺基羰 基]-6-(4-甲基六氩吡畊-1-基)-1Η-蚓哚 使用實施例4之類似方法，自5-(2,6-二曱基吡啶-4-基)萘 -1-基異氰酸酯（D119)和5-氣-2,3-二氫-6-(4-甲基六氫吡 畊-1-基)-1Η-吲哚（D13)製備得白色泡洙標題化合物 (83%)。將其自丙酮中轉換成鹽酸鹽白色固體。 i NMR(自由鹼）(250MHz，CDC13) δ (ppm) ·· 7.98 (d，1H)， 7.83 (s，1H)，7·77·7·69 (m，2H)，7·60-7·38 (m，3H)，7·17 (s， 1H)，7·07 (s，1H)，6.75 (s，1H)，4·25 (t，2H)，3.24 (t，2H)， 3.06 (brm，4H)，2.62 (s，6H)，2.56 (brm，4H)，2.32 (s，3H)。 132 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐）. I------!t-—— (請先閲讀背面之注意事項再本頁) -i'tv 線 經濟部智慧財產局員工消費合作社印製 509687 A7 B7 五、發明説明（131) 經濟部智慧財產局員工消費合作社印製 實施例125 5-溴-2,3-二氩_1-[5-(2,6-二甲基吡啶-4_基)萘-1_基胺基羰 基1-6-(4-甲基六氩吡畊小基)弓丨嗝 使用實施例4之類似方法，自5-(2,6-二甲基吡啶-4-基)萘 -1-基異氰酸酯（D119)和5-溴-2,3-二氫-6-(4-甲基六氫吡 畊小基)-1Η-吲哚（D15)製備得白色泡沫標題化合物 (64%)。將其自丙酮中轉換成鹽酸鹽白色固體。 NMR(自由鹼）(250MHz，CDC13) δ (ppm): 7.98 (d，1H)， 7·84 (s，1H)，7.78-7.68 (m5 2H)，7.6Q-7.38 (m，3H)，7·36 (s， 1H)，7.08 (s，2H)，6.75 (s，1H)，4.25 (t，2H)，3.25 (t，2H)， 3.05 (brm，4H)，2.62 (s，6H)，2.57 (brm，4H)，2·32 (s，3H)。 實施例126 l-[5_(2,6-二甲基-4_吼咬基)-1萘基胺基援基】-5·甲氧基-6-(4-甲基六氩吡畊-1-基)-1Η-吲嗦 使用實施例4之類似方法，自5-(2,6-二甲基吡啶-4-基)萘 -1-基異氰酸酯（D119)和2,3_二氫-5-甲氧基-6-(4-曱基六 氫吡畊-1-基)-1H-吲哚（WO95/06627中間物3)製備得無 油標題化合物（88%)。將其自丙酮中轉換成鹽酸鹽淺黃 色固體。 NMR(自由鹼）(250MHz，CDC13) δ (ppm) ·· 7.99 (d51H)， 7.78 (d，1H)，7.74 (s，1H)，7·68 (d，1Η)，7.60-7.36 (m，3H)， 7.08 (s，2H)，6.76 (s，1H)，6.72 (s，1H)，4.25 (t，2H)，3.85 (s，3H)，3.27 (t，2H)，3.09 (br s，4H)，2.62 (s，6H)，2.57 (br m，4H)，2.32 (s，3H)。 133 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X：297公釐） (請先閱讀背面之注意事項 本頁) -裝· 訂 509687 A7 B7 五、發明説明（132) 實施例127 2,3-二氩小【4-(2,6-二甲基吡啶_3_基)各甲基苯基胺基羰 基】甲氧基_6_(4_甲基六氣吼_小基)-1Η-,鳴 使用實施例4之類似方法，自4-(2,6-二甲基吡啶-3-基)-3-甲基苯胺（D120)和2,3-二氫_5_甲氧基-6-(4-甲基六氫吡 畊-1-基)-1Η-吲哚（WO95/06627中間物3)製備得淺黃色 油標題化合物（44%)。將其自丙酮中轉換成鹽酸鹽橙色 固體。 4NMR(自由鹼)(250MHz，CDC13) δ (ppm) ·· 7·72 (s，1H)， 7·38 (d，1H)，7·32-7·25 (m，2H)，7.07-7.00 (m，2H)，6·74 (s， 1H)，6.43 (s，1H)，4·09 (t，2H)，3.84 (s，3H)，3·20 (t，2H)， 3.15 (br s，4H)，2·65 (br s，4H)，2·58 (s，3H)，2.37 (s，3H)， 2.28 (s，3H)，2·06 (s，3H) 〇 實施例128 5_溴_2,3_二氩甲基·4-(嘆唑-2-基)苯基胺基羰基卜6-(4-甲基六氩吡畊小基)-ιη-吲嘴 使用類似於實施例4之方法，自3-甲基-4-(噻唑-2-基)苯胺 經濟部智慧財產局員工消費合作社印製 (D121)和5-溴_2,3_二氫-6-(4-甲基六氫吡畊小基)-lH-吲哚（D15)製備得泡沫標題化合物（64%)。將其自丙 酮中轉換成鹽酸鹽黃色固體。 'HNMR (HCl^) (400MHz, d6DMSO) δ (ppm) ： 10.74 (br s，1H)，8.75 (s，1H)，7.95 (m，1H)，·7·83 (s，1H)，7·79 (m， 1H) ’ 7.71 (d，1H)，7·61 (s，1H)，7.59 (d，1H)，7.45 (s，1H)， 4·20 (t，2H)，3.45 (d，2H), 3.35 (d，2H)，3·25_3·〇5 (m，6H)， 1341. The paper size of the 1T line is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 509687 A7 B7 5. Description of the invention (130) Example 123 2,3 · Diargon-5-methoxy small [4- (2,6-Dimethylpyridin-4-yl) -3-methylphenylaminocarbonyl] Winter (4-methylhexapyridin-1-yl) -1H-indole Using Example 4 Similar method, from 4- (2,6-dimethylpyridin-4-yl) -3-fluorenylaniline (D88) and 2,3-dihydro-5-fluorenyloxy-6- (4-methyl Hexahydropyridine-1.yl) -1H-indole (WO95 / 06627 intermediate 3) prepared the title compound (95%) as a pale yellow foam. It was converted from acetone to the hydrochloride yellow solid. 4NMR (free base) (250MHz, CDC13) δ (ppm): 7.70 (s, 1H), 7.37 (d, 1H), 7.30 (dd, 1H), 7.14 (d, 1Η), 6.90 (s , 2H), 6.73 (s, 1H), 6.42 (s, 1H), 4.09 (t, 2H), 3.84 (s, 3H), 3.20 (t, 2H), 3.12 (br s, 4H), 2.61 (br s, 4H), 2.56 (s, 6H), 2.34 (s, 3H), 2.27 (s5 3H) 〇 Example 124 5-chloro_2,3-diargon-1_ [5 -(2,6-Dimethylpyridin-4-yl) naphthalene-1 · ylaminocarbonyl] -6- (4-methylhexapyridin-1-yl) -1 fluorene-indole Example 4 Similar method, from 5- (2,6-Difluorenylpyridin-4-yl) naphthalene-1-yl isocyanate (D119) and 5-Ga-2,3-dihydro-6- (4-methylhexa Hydropyrine-1-yl) -1H-indole (D13) prepared the title compound (83%) as a white foam. It was converted from acetone to the hydrochloride salt as a white solid. i NMR (free base) (250MHz, CDC13) δ (ppm) ·· 7.98 (d, 1H), 7.83 (s, 1H), 7.77 · 7 · 69 (m, 2H), 7.60-7 · 38 (m, 3H), 7.17 (s, 1H), 7.07 (s, 1H), 6.75 (s, 1H), 4.25 (t, 2H), 3.24 (t, 2H), 3.06 ( brm, 4H), 2.62 (s, 6H), 2.56 (brm, 4H), 2.32 (s, 3H). 132 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm). I ------! T ----- (Please read the precautions on the back before this page) -i'tv cable Printed by the Employees ’Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A7 B7 V. Description of the Invention (131) Example 125 printed by the Consumers’ Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5-Bromo-2,3-diargon_1- [5- ( 2,6-Dimethylpyridin-4-yl) naphthalene-1_ylaminocarbonylcarbonyl 1-6- (4-methylhexahydropyridine small group). Using a similar method to that in Example 4, since 5 -(2,6-dimethylpyridin-4-yl) naphthalene-1-yl isocyanate (D119) and 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridine) -1H-Indole (D15) prepared the title compound (64%) as a white foam. It was converted from acetone to the hydrochloride salt as a white solid. NMR (free base) (250MHz, CDC13) δ (ppm): 7.98 (d, 1H), 7.84 (s, 1H), 7.78-7.68 (m5 2H), 7.6Q-7.38 (m, 3H), 7 36 (s, 1H), 7.08 (s, 2H), 6.75 (s, 1H), 4.25 (t, 2H), 3.25 (t, 2H), 3.05 (brm, 4H), 2.62 (s, 6H), 2.57 (brm, 4H), 2.32 (s, 3H). Example 126 l- [5_ (2,6-Dimethyl-4_synyl) -1 naphthylamino group] -5 · methoxy-6- (4-methylhexagonyl- 1-yl) -1Η-indionium Using a similar method to that described in Example 4, from 5- (2,6-dimethylpyridin-4-yl) naphthalene-1-yl isocyanate (D119) and 2,3-dihydro 5-Methoxy-6- (4-fluorenylhexahydropyridin-1-yl) -1H-indole (WO95 / 06627 intermediate 3) prepared the oil-free title compound (88%). It was converted from acetone to the hydrochloride pale yellow solid. NMR (free base) (250MHz, CDC13) δ (ppm) 7.99 (d51H), 7.78 (d, 1H), 7.74 (s, 1H), 7.68 (d, 1Η), 7.60-7.36 (m, 3H), 7.08 (s, 2H), 6.76 (s, 1H), 6.72 (s, 1H), 4.25 (t, 2H), 3.85 (s, 3H), 3.27 (t, 2H), 3.09 (br s, 4H), 2.62 (s, 6H), 2.57 (br m, 4H), 2.32 (s, 3H). 133 This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X: 297 mm) (Please read the note on the back page first)-Binding and binding 509687 A7 B7 V. Description of the invention (132) Example 127 2 , 3-Diargon small [4- (2,6-dimethylpyridin_3_yl) each methylphenylaminocarbonyl group] methoxy_6_ (4_methylhexazine_small group)- 1Η-, Ming used a similar method as in Example 4, starting from 4- (2,6-dimethylpyridin-3-yl) -3-methylaniline (D120) and 2,3-dihydro-5_methoxy 6- (4-methylhexahydropyridin-1-yl) -1H-indole (WO95 / 06627 intermediate 3) prepared the title compound (44%) as a pale yellow oil. It was converted from acetone to the hydrochloride orange solid. 4NMR (free base) (250MHz, CDC13) δ (ppm) · 7.72 (s, 1H), 7.38 (d, 1H), 7.32-7 · 25 (m, 2H), 7.07-7.00 (m, 2H), 6.74 (s, 1H), 6.43 (s, 1H), 4.09 (t, 2H), 3.84 (s, 3H), 3.20 (t, 2H), 3.15 (br s, 4H), 2.65 (br s, 4H), 2.58 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H), 2.06 (s, 3H). Example 128 5-Bromo_2,3_diargonylmethyl 4- (anilazol-2-yl) phenylaminocarbonyl group 6- (4-methylhexanidine) -ιη-indole uses similar In the method of Example 4, (D121) and 5-bromo_2,3_dihydro-6- were printed from the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs of 3-methyl-4- (thiazol-2-yl) aniline. (4-methylhexahydropyridine) -1H-indole (D15) was prepared as a foamy title compound (64%). It was converted from acetone to the hydrochloride yellow solid. 'HNMR (HCl ^) (400MHz, d6DMSO) δ (ppm): 10.74 (br s, 1H), 8.75 (s, 1H), 7.95 (m, 1H), 7.83 (s, 1H), 7 · 79 (m, 1H) '7.71 (d, 1H), 7.61 (s, 1H), 7.59 (d, 1H), 7.45 (s, 1H), 4.20 (t, 2H), 3.45 (d, 2H), 3.35 (d, 2H), 3.25-3.05 (m, 6H), 134

本紙張尺度適财_家榡^; 0 x 2^iT 509687 A7 B7 五、發明説明（133) 經濟部智慧財產局員工消費合作社印製 2·84 (d，3H)，2.56 (s，3H)。實施例1295·氣mp.甲基_4_(射_2基)苯基胺基叛基】&amp; (4_甲基六氩吼+1$Mh叫κ 使用類似於實_4之转，自3_甲基_4_(射_2_基)苯胺 (D121)和5-氯办二氫邻麵甲基六氫咖井心·基). ’（D13)製備得米黃色泡沫標題化合物（7〇%)。將 其自丙酮中轉換成鹽酸鹽黃色固體。HNMR (HCl^) (400MHz, d6DMSO) δ (ppm) ： 10.77 (br s，1H) ’ 8·79 (s，1H)，7·93 (d51H)，7·82 (s，1H)，7·79 (d，1H)， 7·71 (d，1H)，7.61 (s，1H)，7.59 (d，1H)，7.29 (s，1H)，4.20 (t，2H)，3.50 (d，2H)，3.34 (d，2H)，3··23·3·04 (m，6H)，2·83 (d，3H)，2·56 (s，3H)。實施例1302,3_二氩-5-甲氡基-l-[3_甲基-4-(嚎唑_2-基)笨基胺基羰 基Η-(Φ·甲基六氩吡喷-i_基)·1Η，哚 使用類似於實施例4之方法，自3-甲基-4-(嗔唑-2-基)苯胺 (D121)和2,3_二氫_5_曱氧基-6_(4-甲基六氫吡畊+基&gt; 1H-吲哚（WO 95/06627中間物3)製備得淺黃色油標題 化合物（68%)。將其自丙酮中轉換成鹽酸鹽黃色固體。 i NMR ( HC1 鹽）（400MHz，d6DMSO) δ (ppm) ·· 10 56 (br 1Η)，8.64 (s51H)，7.94 (d，1H)，7.77 (d51H)，7.69 (d，1H) / 7.65 (s，1H)，7.60 (s，1H)，7.58 (d，1H)，6.92 (s，1H;，4.15(t?2H) ^ 3.77(s,3H) ^ 3.45(brt54H) ^ 3.l4(m?4H) ^ 2.96(t5 135 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閲讀背面之注意事項再本頁) -裝·This paper is suitable for size_ 家 榡 ^; 0 x 2 ^ iT 509687 A7 B7 V. Description of the invention (133) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 2.84 (d, 3H), 2.56 (s, 3H) . Example 1295. Gas mp. Methyl_4_ (radio-2-phenyl) phenylamino group] &amp; (4_methylhexagonal + 1 $ Mh is called κ. It is similar to the real _4, since 3_methyl_4_ (radio_2_yl) aniline (D121) and 5-chloro-dihydro-neighboring methylhexahydrocaline · yl). '(D13) was prepared as a beige foam title compound (7 〇%). It was converted from acetone to the hydrochloride yellow solid. HNMR (HCl ^) (400MHz, d6DMSO) δ (ppm): 10.77 (br s, 1H) '8.79 (s, 1H), 7.93 (d51H), 7.82 (s, 1H), 7. · 79 (d, 1H), 7.71 (d, 1H), 7.61 (s, 1H), 7.59 (d, 1H), 7.29 (s, 1H), 4.20 (t, 2H), 3.50 (d, 2H) , 3.34 (d, 2H), 3 · 23 · 3 · 04 (m, 6H), 2.83 (d, 3H), 2.56 (s, 3H). Example 1302,3-Diargon-5-methylfluorenyl-l- [3-methyl-4- (oxazole_2-yl) benzylaminocarbonylfluorene- (Φ · methylhexaarginyl- i_yl) · 1Η, indole using a method similar to that in Example 4, starting from 3-methyl-4- (oxazol-2-yl) aniline (D121) and 2,3_dihydro-5_fluorenyloxy -6_ (4-methylhexahydropyridine + yl) 1H-indole (WO 95/06627 Intermediate 3) prepared the title compound (68%) as a pale yellow oil. This was converted from acetone to the hydrochloride salt Yellow solid. I NMR (HC1 salt) (400MHz, d6DMSO) δ (ppm) · 10 56 (br 1Η), 8.64 (s51H), 7.94 (d, 1H), 7.77 (d51H), 7.69 (d, 1H) / 7.65 (s, 1H), 7.60 (s, 1H), 7.58 (d, 1H), 6.92 (s, 1H ;, 4.15 (t? 2H) ^ 3.77 (s, 3H) ^ 3.45 (brt54H) ^ 3. l4 (m? 4H) ^ 2.96 (t5 135 This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before this page)-Installation ·

、1T 線 509687 A7 B7, 1T line 509687 A7 B7

2H)，2·81 (d，3H)，2·55 (s，3H)。 實施例131 1-(5-乙醢基萘-1_基胺基羰基)_5-氣·23-二氩-6_(4甲基六 氩吡畊-1_基)-1Η-吲哚 ^ 使用類似於實施例4之方法，自5-乙醯基萘4·基笨胺 (D124)和5-氣-2,3_二氫_6-(4-甲基六氫吡畊小基)_1Η- 吲哚（D13)製備標題化合物。將其轉換成鹽酸鹽米色粉 末。 iHNMR (HC1 鹽）(250MHz，d6DMSO) δ (ppm) : 10.74 (s， 1H)，8·94 (s，1H)，8.46 (d，1H)，8·25 (d，1H)，8·12 (d，1H), 7·74 (s，1H)，7.60 (m，3H)，7·30 (s，1H)，4.32 (br s，2H)， 3.45-2.90 (m，10H)，2.75 (d，6H)。 實施例132 5_氯_2,3-二氩-6-(4-甲基六氩吡畊-i-基)小[5-(嚷啶-2-基氧 基)茶_1_基膝基叛基丨嘴 使用類似於實施例4之方法，自5·-(嘧啶-2-基氧基)萘-1-基胺（D125)和5-氣-2,3_二氫-6_(4-甲基六氫吡畊-1-基)-1H-吲哚（D13)製備標題化合物。將其轉換成鹽酸鹽淺 奶油色粉末（61%)。 lHNMR (HC1 鹽）（250MHz，d6DM@O)5 (ppm) : 10.64(s， 1H)，8·93 (s，1H)，8·64 (d，2H)，7·95 (d，1Η)，7.76 (s，1H)， 7.69-7.39 (m，5H)，7.31 (m，2H)，4.33 (br，2H)，4.33 (br5 2H)，3.45 (m，2H)，3.33-3.10 (m，6H)，2.93 (t，2H)，2·81 (s， 3H) 〇 136 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ----------¾-- (請先閱讀背面之注意事項再¥本頁) 訂 線 經濟部智慧財產局員工消費合作社印製 509687 A7 B7 五、發明説明（135) 實施例133 5-氣-2,3-二氫_6-(4-甲基六氩吡喷小基)小[5-(喊啶各基) 萘-1-基胺基幾基】-lH-ufi喘 使用類似於實施例2之方法，自5-(嘧啶_5_基)萘_丨_基異氰 酸酯（D123)和5-氯_2,3_二氫_6_(4_甲基六氫吡啡·^基)· 1Η-Θ卜朵（D13)製備得白色泡沫標題化合物（43%)。將 其自丙酮中轉換成鹽酸鹽白色固體。 〗HNMR ( HC1 鹽）(40〇MHz，d6DMSO) δ (ppm) : 10·48 (br， 1Η) ’ 9.33 (s，1Η) ’ 8·98 (s，1Η) ’ 8·20 (d，1Η)，7·76 (s，1Η) ’ 7.57-7.67 (m，6H)，7.31 (s，1H)，4·39 (t，2H)，3·43 (2H，受 水峰遮蔽），3.32(d，2H)，3·12_3·24(ηι，4Η)，2.94(t，2H)， 2.80 (d，3H)。 實施例134 2,3-二氩_5-甲軋基_6_(4_甲基六氫吡畊-1_基)-1_[5_(峨啶-5-基)萘-1-基胺基羰基HH-弓丨哚 使用類似於實施例2之方法，自5-(嘧啶-5-基)萘-1-基胺基 罗厌基（D123)和2,3-二氮-5-甲氧基-6-(4_曱基六氮ο比σ井 基)-1Η-吲哚（WO95/06627中間物3)製備得白色泡沫標 題化合物（50%)。將其自丙酮中轉換成鹽酸鹽白色固體。 iNMR ( HC1 鹽）(400MHz，d6DMSO) δ (ppm) : 10.38 (br， 1H)，9.32 (s，1H)，8·98 (s，2H)，8·78 (s，1H)，8·18 (d，1Η)， 7.64(t，1H)，7.58 (m，5H)，6.94 (s，1H)，4.30 (t，2H)，3.77 (s，3H)，3·42 (4H，受水峰遮蔽），3.12-3.23 (m5 4H)，2.89 (t， 2H)，2·78 (d，3H)。 137 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨〇'〆297公釐) (請先閲讀背面之注意事項再ml:本頁) 秦· 經濟部智慧財產局員工消費合作社印製 509687 A7 _ B7 五、發明説明（136) 經濟部智慧財產局員工消費合作社印製 實施例1355-氯-H5-氟基萘小基胺基羰基)-2,3·二氩_6-(4-甲基六氩 吡畊-1-基)-1H-弓丨哚 使用類似於實施例4之方法，自5-氰基萘-1-基胺（D126) 和5-氣-2,3-二氫-6_(4-甲基六氫吡啡_1-基）_iH- $卜朵 (D13)製備標題化合物。將其轉換成鹽酸鹽奶油色粉末 (81%)。 iHNMiK 自由鹼）(250MHz，CDC13)S (ppm):8.17(d，1H)， 8.11 (d，1H)，7.91 (d，1H)，7.80 (m，2H)，7.70 (t，1H)，7·56 (t，1H)，7·18 (s，1H)，6·71 (s，1H)，4.25 (t，2H)，3·26 (t，2H)， 3·07 (br s，4H)，2.59 (br s，4H)，2.34 (s5 3H)。實施例1365-氣-2,3-二氩-l-[5-(5-甲基-1，2,4-今二峻-3-基)萘-1_ 基胺 基羰基H_(4_甲基六氩吡喷小基)_1Η·吲哚 使用實施例4之類似方式，自5-(5-甲基-1，2,4-畤二唑-3-基)萘小基胺（D130)和5-氣-2,3·二氫-6-(4_甲基六氫吡畊 -1-基)-1Η-吲哚（D13)製備標題化合物。將標題化合物轉 換成其鹽酸鹽米色粉末（84%)。 iNMR (HC1 鹽）（250MHz，d6DMSO) δ (ppm) ·· 10.67 (s， 1H)，8·98 (s，1H)，8·65 (d，1H)，8.28 (d，1H)，8.19 (d，1H)， 7·75-7·61 (m，4H)，7.31 (s，1H)，4.31 (t，2H)，3.33-3.13 (m， 6H)，2·97 (t，2H)，2.80 (s，3H)，2.75 (s，3H)。2H 訊號受 到H20訊號遮蔽。 築理數據 138 本紙張尺度適用中國國家榡準（〇阳）八4規格（210/297公釐）· (請先聞讀背面之注意事項再mb本頁) .裝· 訂 線 509687 A7 B7 五、發明説明（137 經濟部智慧財產局員工消費合作社印製 5~HT1a、5-HTm 受體結合 將表現5-HT1A受體（4xl〇7/毫升）之HEK293細胞於 Tris緩衝劑中均質化，並儲存於1毫升水份中。將表現 5-HT1B受體（4xl07細胞/毫升）之CHO細胞於Tris缓衝 劑中均質化，並儲存於1·5毫升水份中。將表現5-HTm 受體（0·563χ108/毫升）之CHO細胞於Tris緩衝劑中均質 化，並儲存於1毫升水份中。 於37 C時’將0.4毫升細胞懸浮液和存於TrisMgHCl 緩衝劑(pH 7·7)之用於5-HT1B/1D受體之[3H]_5-HT (4nM)及 用於5-HT1A受體之[3H]_8-0H DPAT (InM)，以及試驗藥 物培養45分鐘。於l〇個濃度（〇·〇ι mM至最終濃度0·3 ηΜ)下，對各個試驗藥物進行測試，同時以使用0 01mM 5-HT來定義非專一性結合。總分析體積為〇·5毫升。使用 帕卡德過濾伴器（將濾器預浸於〇·3 %聚乙烯亞胺）迅速 過濾而停止溫育，並經由尖端計數閃爍計數測量放射活 性。經由反覆最小平方曲線擬合程式自IC5Q計算得pKi 值。 於5_HT1A、5-HT1B* 5-町10受·體時，實施例5、9、 10、15、21、24、25、27、28、43、44、45、47、48、49、 50、52、53、67、68、69、70、7卜 72、76、78、80、8卜 82、83、89、97、98 和 110 具有 pKi 值〉8.0。 139 本紙張尺度適用中國國家樣準（CNS )八4祕（21〇χ297公襲）2H), 2.81 (d, 3H), 2.55 (s, 3H). Example 131 1- (5-Ethylnaphthalene-l-ylaminocarbonyl) -5-gas23-diargon-6- (4-methylhexanaphthyl-1 -yl) -1fluorene-indole ^ used Similar to the method of Example 4, from 5-ethenylnaphthalene 4-ylbenzylamine (D124) and 5-gas-2,3-dihydro-6- (4-methylhexahydropyridine) _1 小-Indole (D13) to prepare the title compound. It was converted into a hydrochloride beige powder. iHNMR (HC1 salt) (250MHz, d6DMSO) δ (ppm): 10.74 (s, 1H), 8.94 (s, 1H), 8.46 (d, 1H), 8.25 (d, 1H), 8.12 (d, 1H), 7.74 (s, 1H), 7.60 (m, 3H), 7.30 (s, 1H), 4.32 (br s, 2H), 3.45-2.90 (m, 10H), 2.75 ( d, 6H). Example 132 5-Chloro_2,3-diargon-6- (4-methylhexapyridine-i-yl) small [5- (pyridin-2-yloxy) tea_1-based knee The radical was used in a manner similar to that in Example 4, starting from 5 ·-(pyrimidin-2-yloxy) naphthalen-1-ylamine (D125) and 5-Ga-2,3_dihydro-6_ ( 4-methylhexahydropyridin-1-yl) -1H-indole (D13) to prepare the title compound. It was converted into a hydrochloride light cream powder (61%). lHNMR (HC1 salt) (250MHz, d6DM @ O) 5 (ppm): 10.64 (s, 1H), 8.93 (s, 1H), 8.64 (d, 2H), 7.95 (d, 1Η) , 7.76 (s, 1H), 7.69-7.39 (m, 5H), 7.31 (m, 2H), 4.33 (br, 2H), 4.33 (br5 2H), 3.45 (m, 2H), 3.33-3.10 (m, 6H), 2.93 (t, 2H), 2.81 (s, 3H) 〇136 This paper size applies to China National Standard (CNS) A4 (210X297 mm) ---------- ¾-- (Please read the precautions on the back of this page before ¥ this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, printed 509687 A7 B7 V. Description of the invention (135) Example 133 5-Gas-2,3-dihydro_6 -(4-methyl hexahydropyridine) small [5- (allyl) groups of naphthyl-1-ylamino] -lH-ufipan using a method similar to that in Example 2, starting from 5- (Pyrimidine_5_yl) naphthalene_ 丨 _yl isocyanate (D123) and 5-chloro_2,3_dihydro_6_ (4_methylhexahydropyridine. ^ Yl) · 1Η-Θ BUDO (D13 ) The title compound (43%) was prepared as a white foam. It was converted from acetone to the hydrochloride salt as a white solid. HNMR (HC1 salt) (40 MHz, d6DMSO) δ (ppm): 10.48 (br, 1Η) '9.33 (s, 1Η)' 8.98 (s, 1Η) '8 · 20 (d, 1Η ), 7.76 (s, 1Η) '7.57-7.67 (m, 6H), 7.31 (s, 1H), 4.39 (t, 2H), 3.43 (2H, shaded by water peaks), 3.32 ( d, 2H), 3 · 12_3 · 24 (η, 4Η), 2.94 (t, 2H), 2.80 (d, 3H). Example 134 2,3-Diargon-5-methylpentyl-6_ (4-methylhexahydropyridine-1_yl) -1_ [5_ (eridin-5-yl) naphthalene-1-ylamino The carbonyl HH-quinone indole was similar to that used in Example 2 from 5- (pyrimidin-5-yl) naphthalen-1-ylaminoronoryl (D123) and 2,3-diaza-5-methoxy -6- (4-fluorenylhexazolium ratio σ well-based) -1 fluorene-indole (WO95 / 06627 intermediate 3) to prepare the title compound (50%) as a white foam. It was converted from acetone to the hydrochloride salt as a white solid. iNMR (HC1 salt) (400MHz, d6DMSO) δ (ppm): 10.38 (br, 1H), 9.32 (s, 1H), 8.98 (s, 2H), 8.78 (s, 1H), 8.18 (d, 1Η), 7.64 (t, 1H), 7.58 (m, 5H), 6.94 (s, 1H), 4.30 (t, 2H), 3.77 (s, 3H), 3.42 (4H, water receiving peak Shading), 3.12-3.23 (m5 4H), 2.89 (t, 2H), 2.78 (d, 3H). 137 This paper size is in accordance with Chinese National Standard (CNS) A4 (2 丨 〇'〆297mm) (Please read the precautions on the back before ml: this page) Printed by Qin · Ministry of Economic Affairs Intellectual Property Bureau Employee Consumption Cooperative 509687 A7 _ B7 V. Description of the invention (136) Example 1355-Chloro-H5-fluoronaphthalene small ylaminocarbonyl group printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs-2,3 · Diargon 6- (4- Methylhexanaphthyl-1-yl) -1H-toxin, using a method similar to that in Example 4, from 5-cyanonaphthalene-1-ylamine (D126) and Hydrogen-6- (4-methylhexahydropyridin_1-yl) -iH- $ Budor (D13) The title compound was prepared. Converted to hydrochloride cream powder (81%). iHNMiK free base) (250MHz, CDC13) S (ppm): 8.17 (d, 1H), 8.11 (d, 1H), 7.91 (d, 1H), 7.80 (m, 2H), 7.70 (t, 1H), 7 · 56 (t, 1H), 7.18 (s, 1H), 6.71 (s, 1H), 4.25 (t, 2H), 3.26 (t, 2H), 3.07 (br s, 4H ), 2.59 (br s, 4H), 2.34 (s5 3H). Example 1365-Gas-2,3-Diargon-l- [5- (5-methyl-1,2,4-glycero-3-yl) naphthalene-1-ylaminocarbonylcarbonyl H_ (4-methyl Hexahydropyridine) _1Η · indole In a similar manner as in Example 4, from 5- (5-methyl-1,2,4-fluorenediazol-3-yl) naphthalene small amine (D130) And 5-Gas-2,3.dihydro-6- (4-methylhexahydropyrine-1-yl) -1fluorene-indole (D13) to prepare the title compound. The title compound was converted into its hydrochloride beige powder (84%). iNMR (HC1 salt) (250MHz, d6DMSO) δ (ppm) 10.67 (s, 1H), 8.98 (s, 1H), 8.65 (d, 1H), 8.28 (d, 1H), 8.19 ( d, 1H), 7.75-7.61 (m, 4H), 7.31 (s, 1H), 4.31 (t, 2H), 3.33-3.13 (m, 6H), 2.97 (t, 2H), 2.80 (s, 3H), 2.75 (s, 3H). The 2H signal is blocked by the H20 signal. Construction data 138 This paper size is applicable to China National Standard (Oyang) 8 4 specifications (210/297 mm) · (Please read the precautions on the back before mb this page). Binding · 509687 A7 B7 5 2. Description of the invention (137 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, 5 ~ HT1a, 5-HTm receptor binding will homogenize HEK293 cells expressing 5-HT1A receptor (4x107 / ml) in Tris buffer, And stored in 1 ml of water. CHO cells expressing 5-HT1B receptor (4x107 cells / ml) were homogenized in Tris buffer and stored in 1.5 ml of water. 5-HTm Receptor (0.563 x 108 / ml) CHO cells were homogenized in Tris buffer and stored in 1 ml of water. At 37 C, 0.4 ml of the cell suspension and TrisMgHCl buffer (pH 7 · 7) [3H] _5-HT (4nM) for 5-HT1B / 1D receptor and [3H] _8-0H DPAT (InM) for 5-HT1A receptor, and test drug culture for 45 minutes. Each test drug was tested at 10 concentrations (0.0 mM to final concentration 0.3 ηM), while non-specific binding was defined by using 0.01 mM 5-HT The total analysis volume was 0.5 ml. The incubation was stopped by rapid filtration using a Packard filter companion (pre-soaked the filter with 0.3% polyethyleneimine), and radioactivity was measured by tip count scintillation counting. Repeatedly The least square curve fitting program calculates the pKi value from IC5Q. In the case of 5_HT1A, 5-HT1B * 5-machi 10 receptors, Examples 5, 9, 10, 15, 21, 24, 25, 27, 28, 43 , 44, 45, 47, 48, 49, 50, 52, 53, 67, 68, 69, 70, 7, 72, 76, 78, 80, 8 82, 83, 89, 97, 98, and 110 have pKi Value> 8.0. 139 This paper size is applicable to China National Sample Standard (CNS) 8th secret (21〇χ297 public attack)

(請先閲讀背面之注意事項V 裝II Γ本頁) 訂-(Please read the Precautions on the back V Pack II Γ page) Order-

Claims (1)

509687509687 六、申請專利範圍 Μ利申請案第87105843號 RCg Patent Appln. No. 87105843 專利範圍屮义本 -Pf、j 件 _ Amended Claims in Chinese - Enel. ~(~89 年4月&gt;|曰it 呈）— (Submitted on April &gt;1，2000) 種式(Γ)之化 鹽類：Sixth, the scope of the patent application, the patent application No. 87105843, RCg Patent Appln. No. 87105843, the scope of the patent-Pf, j pieces _ Amended Claims in Chinese-Enel. ~ (~ April 89 &gt; | ) — (Submitted on April &gt; 1, 2000) Chemical salts of formula (Γ): 其中Ra為具式(i)之基r1Y7v -&quot;ΐ?ιπ (R )a (i) 其中 ，： P1為苯基、萘基、喳啉基、或四氳異喳啉基； R1及R2分別獨立地為氫、鹵素、CK6烷基、氰基或 Cp6烷氧基羰胺基； a為1或2 ; 或Ra為具式(ii)之基 7) 佐，丨 . 裝#. ~. (請先閲讀背面之注意事項再填寫本頁) (ϋ) 經濟部智慧財產局員工消費合作社印製 其中 P2和P3獨立地為苯基、萘基、噻吩基、呋喃基、咪 ΰ坐基、噚峻基、吼嗤基、嗔哇基、喝二嗤基、癌 啶基、嗒畊基、吡畊基、吡啶基、六氫吡啶基、 喳σ林基、異喳啉基、或四氳異喳咁基； 140 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 509687 ABCD ττ、申請專利乾圍 (請先閱讀背面之注意事項再填寫本頁) Α為一鍵結或氧、-CHrCH2-、或NR4，其中R4為氫 或C^6烷基； R1、R2和R3分別獨立地為氳、鹵素、CK6烷基、Cy 烷醯基或氰基； Y 為-NH-或-CH2-; W 為-CHCH-或-(CH2)r，其中 t 為 2 或 3 ; Rb為氫、鹵素、CV6烷基、三氟甲基、€^6烷氧基、 或C2_6烯基； Re為氳或CU6烷基。 2. 根據申請專利範圍第1項之式(Γ)化合物，其中R1為 鹵素原子。 3. 根據申請專利範圍第1或2項之式(Γ)化合物，其中 R2及/或R3各自為氫、鹵素、或CK6烷基。 4. 根據申請專利範圍第1或2項之式(Γ)化合物，其中 P1及P2為笨基、萘基或喳啉基。 5. 根據申請專利範圍第1或2項之式(Γ)化合物，其中 Y 為-NH-。 6. 根據申請專利範圍第1或2項之式(Γ)化合物，其中 W為具式-(CH2)2•之基團。 經濟部智慧財產局員工消費合作社印製 7. 根據申請專利範圍第1或2項之式(Γ)化合物，其中 圮為心^烷氧基。 8. 根據申請專利範圍第1項之式(Γ)化合物，其係： 1 -[(4-溴-3_甲苯基)胺基羰基]-5-甲氧基-6-(4-甲基六 氫吡畊-1-基)-m-吲哚， 141 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 509687 A8 B8 C8 D8 TC、申請專利乾圍 (請先閱讀背面之注意事項再填寫本頁) l-[(4-溴各甲苯基)胺基羰基]-2,3-二氫-5-曱氧基-6-(4-甲基六氮。比ϋ井-1-基5 1-[(2,3-二氯苯基)胺基綠基]-2,3-二氮-5-甲氧基-6-(4-甲基六氮ϋ比11井-1-基)-111-5111 朵， 2.3- 二鼠-5-曱氧基-6-(4-曱基六鼠吼井-1-基)-144-(13比 啶-4-基)萘-1-基胺基羰基]-1H-吲哚， 2.3- 二氳-5-甲氧基-6-(4-甲基六氫吡畊小基)-1-[5-(吡 啶-4-基)萘-1基胺基羰基]_1H-吲哚， 1-[(2,3-二氣-4-(11比11 定-4-基)苯基胺基幾基]-2,3_二鼠-5-甲氧基-6-(4-甲基六氫吡畊-1-基)-1H-吲哚， 2.3- 二氮-5-甲氧基-6-(4-甲基六風〇比口井-1-基)-l-(tI奎σ林-5-基胺基羰基 )-1Η-吲哚， 2.3- 二氮-6-(4-甲基六氮口比1^·1-基)-1-[4-(喻0定-4-基)奈 -1-基胺基羰基)_1Η-吲哚， 5-氯-2,3_二氮-6-(4-甲基六氮11比σ井-1-基)-1-[4-(°比唆-4-基)萘-1-基胺基羰基)-1仏吲哚， 5賺&gt;臭_2,3_二鼠_6讎(4_曱基六鼠口比口井-1_基)_1雜[4-( 口比口定_4-基)蒸-1-基胺基魏基)-1Η-Ί卜朵’ 經濟部智慧財產局員工消費合作社印製 5-&gt;臭-2,3-二風-6-(4_甲基六風吼〇井-1-基)-1_[4-(σ比咬-4-基)苯基胺基羰基]-m-吲哚， 5-&gt;臭-1-[3-氣-4-(11比唆-4_基)苯基胺基魏基]_2,3-二鼠-6-(4_甲基六氫吡畊-1-基)-1Η_吲哚， 2.3- 二氮-5-甲基-6-(4-甲基六鼠。比啡-1-基)-1-[4-(σ比唆_ 4-基)蓁-1-基胺基羰基]_1Η-吲哚， 142 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 經濟部智慧財產局員工消費合作社印製 刈9687 A8 B8 C8 ----------- - D8 — ........................................................................................................-............................-........................ — 六、申請專利範圍 H3_氯冰(吡啶-4-基)苯基胺基羰基]_2,3_二氫|甲基 -6_(4-甲基六氫吡畊小基)-iH-吲哚， 2.3- 二氫-6_(4-甲基六氳吡畊小基)小[4-(吡啶冰基)萘 基胺基羰基]_5_乙烯基-1H-吲哚， 2,3·一氮-5-乙基-6-(4-甲基六氮ϋ比17井-1•基)-1-[4-(σ比!1定_ 基)萘-1-基胺基羰基]-1Η-吲哚， Η3-氯冬(吼啶-4-基)苯基胺基羰基]-2,3_二氫-5_乙基 -6-(4-甲基六氫吡啡小基)-ΐΗ_吲哚， 2.3- 一鼠-6-(4-甲基六氫》比σ井-1-基)_1-[4-(吼咬《4-基)萘 -1-基胺基羰基]_5_三氟甲基-1Η-吲哚， 1_[3_氯_4-(吡啶-4-基)苯基胺基羰基]-2,3-二氫-6-(4-甲 基六氫吡畊·1_基)-5-三氟甲基-1H-吲哚， 2.3- 二氫-5-甲氧基-6-(4-甲基六氫吡畊-1-基)小[4-(吡 啶冰基)萘基乙醯基]-1H-吲哚， ： 2.3- —鼠-5_甲氧基_6_(4_甲基六氮σ比啡-1-基比 啶-4-基)-萘-1_基乙醯基；]_ιη_吲哚， 2,3_二氫-6-(4_甲基六氫吡啡-1-基)_1-[4_(吡啶-4-基)萘 -1-基乙醯基]-1Η-吲哚， 5-氣一 風-6-(4-甲基六氮 口 比口井-1-基)-1«&quot;[4-(口比咬-4·» 基)萘-1-基乙醯基]-1Η-吲嗦， 5-溴-2,3_二氫-6-(4-甲基六氫咐讲-1-基)小[4·(吼咬一4-基)萘小基乙醢基]朵， 2.3- 二氫-6-(4-甲基六氫吡畊-1-基)小[4-(吡啶_4_基)萘 小基乙醯基]麵5麵乙烯基-1H-, 口朵， 143 本纸張尺度適用中關家標準（CNS ) A4· ( 21GX297公釐) '~~ I I— 訂 Aw (請先閲讀背面之注意事項再填寫本頁) 申請專利範圍 Α8 Β8 C8 D8 經濟部智慧財產局員工消費合作社印製 5-溴-2,3-二氫_6-(l-甲基六氫吡畊-4-基)-1-[4-(吡啶-4-基)奈-1-基胺基魏基]-1H-弓卜朵， 5- 氯-2,3-二氫-6-(4-甲基六氫吡畊小基)小[5-(吡啶-4-基)萘-1-基胺基羰基]-1Η-吲哚， 5_溴-2,3-二氫-6-(4-甲基六氫吡畊小基)小[5-(吡啶-4-基)萘小基胺基羰基HH-吲哚， 2.3- 二鼠-5_曱氧基-6-(4•曱基六氫σ比σ井-1-基林- 6- 基胺基羰基)-1Η-吲哚， 2.3- 二氫小[4-(第三-丁氧基羰基胺基)苯基胺基羰基]-5-氯-6-(4-甲基六氫吡畊_1_基)-1Η-吲哚， 5- 溴_2,3-二氫-6_(4-曱基六氫吡啡小基)小(喳啉-6-基 胺基羰基)-1Η-吲哚， 6- 溴-7_(4-曱基六氫吡口井小基)-1_[4-(吼啶-4-基)萘小 基胺基羰基]-1，2,3,4·四氫喳啉， 5_氣-2,3-二風-6-(4-甲基六氮吼11井-1-基)-1_(4_苯氧墓 苯基胺基羰基)-1Η-吲哚， 5-氟_2,3-二氮-1-[4-(4-氣苯氧基)苯基胺基援基)_6-(4· 甲基六氫吡畊小基)-1Η-吲哚， 5-氯-2,3-二氫各(4_甲基六氫吡畊小基)小(喳咁-6-基 胺基羰基)-1Η-吲哚， 5-氯-2,3-二氳·6·(4_甲基六氫吼畊-1-基)·1_(3-笨氧基 苯基胺基羰基)-1Η-吲哚， 5-氣-2,3-二氮-6-(4-甲基六虱σ比11 井-1-基)-1-[4-(哺咬-2·* 基)苯基胺基羰基]-1Η-吲哚， 144 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) L r •1— » 509687 A8 B8 C8 D8 六、申請專利範圍 (請先閲讀背面之注意事項再填寫本頁) 1-(3-苄氧基苯基胺基羰基)-5-氣-2,3-二氫-6-(4-甲基 六氫吡畊-1-基)-1Η-吲哚， 1 -(4-苄氧基苯基胺基羰基)-5-氯-2,3-二氳-6-(4-甲基 六氫吡畊-1-基)-1Η-吲哚， 5-氯ι-2,3-二鼠-6-(4-甲基六鼠11比°井_1_基)-1-(2-甲基口奎 啉-6-基胺基羰基)-m-吲哚， 5-氯-2,3-二氮-1-[4-(咬喃-2-基)苯基胺基幾基]-6-(4-甲 基六氮吼11井-1-基)-1Η-弓卜朵’ · 5-氣-2,3-二鼠-6-(4-曱基六鼠°比啡-1_基)-1-[4-(ϋ塞吩-2_ 基)苯基胺基羰基]-1Η-吲哚， 5-氣-2,3-二鼠-6-(4-甲基六鼠 ^^-1-基)-1-0-(11 比咬-4-基)蒸基乙酿基]-1H-叫丨σ朵’ 5-&gt;臭-2,3-二鼠-6-(4-甲基六 基定-4_ 基)蒸-1-基乙酿基]-lH-p弓卜系’ 5-氣-2,3-二氮甲基六氮11比。井-4-基)茶-1-基於 基幾基]-6-(4-甲基六氮11比11 井_1_基)-1Η_弓丨1^ ’ 5- 氣-2,3·二氫小[4-(2-甲基啐唑-4-基)苯基胺基羰基]- 6- (4-甲基六鼠口比口井-1-基)-1Η-ρ引11 朵， 經濟部智慧財產局員工消費合作社印製 5-&gt;臭_2,3_二風-6-(4-甲基六風11比σ井-1-基)_1-[4-(2-甲基 吡啶-4-基)苯基胺基-羰基]-1Η-吲哚， 5-氯-2,3-二氮-6-(4-甲基六風σ比啡_1_基)-1-[4-(2-甲基 吡啶-4-基)苯基胺基羰基]-1Η-吲哚， 5-氯_2,3·二氳-1·[4_(2,6-二甲基吡啶-4-基)苯基胺基羰 基]-6-(4-甲基六氫吡畊_1_基)-1Η-吲哚， 145 本紙張尺度適用中國國家標準（CNS ) Α4規格（2i0X297公釐） V7VJ〇 / A8 B8 C8 --—〜 _D8 . 、申請專利範圍 臭-·2,3-二氫-l-[4-(2,6_二甲基口比。定《4-基)苯基胺基罗炭 基；h6-(4-曱基六氳吡畊-1-基)-1Η-吲哚， 2,3-二氫小[4-(2,6-二甲基吡啶冰基)苯基胺基羰基]_ 5-甲氣基-6-(4-甲基六鼠基)-ΙΗ-π引。朵， 5遗-2,3-二氫-1_[4-(2,6_二甲基吡啶_3_基)苯基胺基羰 基]«4-甲基六氫吡畊-1-基)-1Η-吲哚， 溴_2,3_二氫小[4_(2,6_二曱基吡啶各基)苯基胺基羰 基&gt;6-(4-甲基六氫吡畊-1-基)-1Η-吲哚， 2少二氫-l_[4-(2,6-二甲基吡啶-3-基)苯基胺基羰基]_ 5_甲氣基-6-(4-甲基六鼠11比口井-1-基)-1Η-叫卜朵， 5-氣-2,3-二氮-6-(4-甲基六氮11比讲-1_基)-1-[4-(5-甲基_ 1，2,4_畤二唑-3-基)苯基胺基羰基]-1Η-吲哚， 5-乳-2,3-二氫-1-[4-(3-甲基_1，2,4-崎二嗤_5-基)苯基胺 基羰基]-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚， 5-氯-2,3-二氫-6-(4_甲基六氫吡畊-1·基)-1-[3-(嘧啶4 基氧基)苯基胺基羰基]_1H-吲哚， 5-氣-2,3-二氮-6-(4_甲基六氮σ比11 井-1-基)-1-{4«Ν_甲基_ N-(嘧啶-2-基)胺基]苯基胺基羰基}-1Η-吲哚， 5-&gt;臭-2,3-二氮-1_[4-(咬喃-2-基)苯基胺基#炭基]-6-(4-甲 基六氮11比13井-1-基)-1Η-弓卜朵’ 5-氯_2,3-二氫-6-(4-甲基六氫吡畊-1-基)小[4-(噻吩-3-基)苯基胺基毅基]-1H-1卜朵’ 5-溴_2,3_二氫-6-(4-甲基六氫吡啡小基)-1_[4_(噻唑_2_ 基)苯基胺基羰基]·1Η-吲哚， 146 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） (請先閲讀背面之注意事項再填寫本頁) -訂 經濟部智慧財產局員工消費合作社印製 509687 ABCD 六、申請專利範圍 (請先閲讀背面之注意事項再填寫本頁) 5-氣-2,3-二氫-6-(4-甲基六氫吡畊-1-基)小[4-(噻唑-2-基)苯基胺基纟炭基]-1H-5卜朵’ 1-[4-(5-乙醯基噻吩-2-基)苯基胺基羰基]-5-氯-2,3-二 氫-6-(4-甲基六氫吡畊-1-基)-1H-吲哚， 1-(5-》臭奈-1_基乙酿基)-5 -氯-2,3-二氮-6-(4-甲基六氮 吡畊-1-基)-1Η-吲哚， 5-氯-2,3-二鼠-6-(4-甲基六鼠1^ ϋ井-1 -基)-1-(8-苯基ϋ奎 咁-5-基胺基羰基]-1Η-吲哚， 5-&gt;臭-2,3-二氣-6_(4-甲基六氮11比11井-1-基)-1-(8-苯基0奎 啉-5-基胺基羰基]-1H·吲哚， 5-氯_2,3_二氫-6-(4-甲基六氳吡畊-1-基)小[2-(2·苯基 乙基)喳啉-6-基胺基羰基]-1H-吲哚， 5_氯-2,3-二鼠-6-(4-甲基六鼠吼。井-1-基)-1-[5-(1-曱基 六氫吡畊斗基)萘-1-基胺基羰基]_m-吲哚， 5-漠-2,3-二氮-1-[4-(異啥ϋ林-4-基)苯基胺基幾基]-6-(4_ 甲基六氮吼啡-1-基)_1Η-0引朵， 5·氣-2,3-二氮-1_[4_(異唆咐-4_基)苯基胺基幾基]-6_(4_ 甲基六氮吼11井-1-基)-1Η-&lt;σ朵， 經濟部智慧財產局員工消費合作社印製 5-溴-2,3-二氫-6-(4_甲基六氫吡畊-1-基)-1_[4-(喳咁-3-基)苯基胺基羰基]-1Η-吲哚， 5-氯-2,3-二氫-6-(4-甲基六氫吡啩-1-基)-1-[4-(喳啉-3-基)苯基胺基羰基]-1Η-吲哚， 5-氯_2,3_二風-6-(4_甲基六鼠ϋ比σ井-1-基)-1_[2-甲基~ 1，2,3,4-四氫異喳啉-7-基)胺基羰基]-1Η·吲哚， 147 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 509687 ABCD 經濟部智慧財產局員工消費合作社印製 六、申請專利範圍 5-溴-2,3-二氫-6-(4-甲基六氫吡畊-1 -基)_ 1 -[2-甲基-1，2,3,4-四氫異咹啡-7-基)胺基羰基]-1Η-吲哚， 5-&gt;臭-2,3-—風-6-(4-甲基六氮。比讲-1_基)-1-[4-(咬。林-8-基)苯基胺基羰基ΗΗ-吲哚， 5-氣-2,3-^—氮-6-(4-曱基六氮口比®井-1-基)-1-[4-(啥咐-8-基)苯基胺基羰基]-1Η·吲哚， 5-氣-2,3-二氳小[4_(咪吐-1_基)苯基胺基幾基]-6-(4-甲 基六氫吡畊-1-基)_1H-吲哚， 5-氣-2,3-二鼠_6_(4-曱基六風17比1^井_1_基)-1-[4-(σ比咬-4-基)苯基胺基羰基]-1Η-吲哚， 2.3- 二氮-5-甲氧基-6-(4-甲基六氮1^比11 井-1-泰)-1-[(8-苯 基喳咁-5-基)胺基羰基]-1H-吲哚， 5-氣-2,3-二氫-6-(4-甲基六氫吡畊小基)小[(8-苯基喳 咁斗基)胺基羰基]_111_吲哚， 5-溴-2,3-二氫各(4-甲基六氫吡畊-1-基)_1-[(8_苯基喳 啉-4-基)胺基羰基]_1H-吲哚， 2.3- 二氫-5_甲氧基-6-(4-甲基六氫σ比11 井-1-基)-1-[(8-苯 基喳啉-4_基)胺基羰基]-1Η-吲哚， 5-氯-2,3-二氫小[4-(2,6-二曱基-六氳吡畊冰基)各甲 基笨基胺基羰基]冬(4-甲基六氫吡畊-1-基)-1Η-吲 哚， 5·氣-2,3-二氫-1-[3-甲基-4-(6-甲基吡啶-2-基)苯基胺 基幾基]-6-(4-甲基六氫 5-溴_2,3_二氫小[3-甲基-4-(6-甲基吡啶-2_基)苯基胺 148 本紙張尺度顧t關準（CNS ) Α4·/( 210X297公 (請先閱讀背面之注意事項再填寫本頁) 509687 A8 B8 C8 D8 六、申請專利範圍 基幾基]-6-(4-甲基六氮吼°井_1_基)-1Η_1|ϋ朵》 2.3- 二氫-5-甲氧基小[3-甲基斗(6-甲基吡啶-2-基)苯 基胺基羰基]-6-(4-甲基六氫吡畊小基ΗΗ-吲哚， 5-氯-2,3-二氫小[5-(6-甲基吼唆-2-基)萘小基胺基幾 基]-6-(4-曱基六氫咕畊-1-基)-1H-吲哚， 2.3- 二氫-5-甲氧基-1-[5-(6-甲基吡啶-2-基)萘小基胺 基羰基]_6-(4-甲基六氫吡畊小基)-1Η-吲哚， 5-氣_2,3_二鼠-6-(4-乙基六氮。比。井-1-基)-1-[4-(σ比σ定 基)萘小基胺基羰基ΗΗ-吲哚， 5-氣·2,3_二氣-6-(4-乙基六氮吼σ井-1-基)_ι_[5-(ιι比。定_4_ 基)萘-1-基胺基羰基]-1Η-吲哚， S-氣_2,3·二氫_6_(六氫吼0井-1·基)-l-[4-(u比咬冰基)蒸· 1-基胺基羰基]_1H-吲哚鹽酸鹽， 5_氯-2,3-二氫-6-(六氫吼u井-1-基)小[5-(吼咬-4-基)萘-1-基胺基羰基]-1Η-吲哚鹽酸鹽， - 5-氣-2,3-二氫-6-(4-甲基六氫。比σ井4-基)-1-[4十荅啡-3- 基)苯基胺基羰基]-1Η-吲哚， 5-溴-2,3_二氫-6-(4-甲基六氫吡畊小基)小[4-(嗒呼一3_ 基)苯基胺基羰基]-1Η-吲哚， 5-氯_2,3-二氫-6_(4_曱基六氫吡畊_1_基)-1_[冬(吡叫:_2_ 基)苯基胺基羰基]-1Η-吲哚， 5_溴-2,3-二氫-6-(4-甲基六氫吼畊-1-基)-1-[4-(σ比σ井_2_ 基)苯基胺基羰基ΗΗ-吲哚， 5-氣-2,3-二氫_6_(4_甲基六氫σ比σ井小基)-1_[(2_苯基吼 149 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公羡) 一- ^-------- (請先閲讀背面之注意事項再填寫本頁) -!·&lt;»· L·. 經濟部智慧財產局員工消費合作社印製 509687 A8 B8 C8 D8 六、申請專利範圍 啶-5-基)胺基羰基]_1Η-吲哚， (請先閲讀背面之注意事項再填寫本頁) 5-&gt;臭-2,3-二氣-6-(4-甲基六鼠吼11井-1-基)-1-[(2-苯基1:|比 咬-5-基)胺基戴基]-1H-㈤。朵^ 5- 氯-2,3-二鼠-l-[4-(6-甲基σ荅喷-3-基)苯基胺基綠基]_ 6- (4-曱基六氫吡畊-1-基)-1Η-吲哚， 5- &gt;臭-2,3_二氮-l-[4-(6-甲基塔。井-3-基)苯基胺基辕基]_ 6- (4-甲基六氮口比11井-1-基)_1Η-0引σ朵， 5-氯-2,3-二氮-6-(4-甲基六鼠〇比〇井-1-基)-1-[4-(〇比0定-3-基)苯基胺基羰基]1H-吲哚， 5- 氯-2,3-二氫-l-[4-(5-甲基噚唑-2-基)苯基胺基羰基]-6_(4_甲基六氮。比11井-1-基)-111-1?引!1朵’ 2,3-二氮-5-曱氧基-1-[4_(5•曱基σ亏嗤-2-基)苯基胺基 羰基]-6-(4-甲基六氫吡畊-1-基)-1Η-吲哚， 5_溴-2,3-二氫_1-[4-(5•甲基畤唑-2-基)苯基胺基羰基]· 6- (4-甲基六氮吼井-1_基)_1Η-弓卜朵’ 5- 氯-2,3-二氮-1-[4-(1-甲基。比°坐-4-基)苯基胺基讓基]_ 6- (4-甲基六氫吡畊小基)-m-吲哚， 5-&gt;臭-2,3-二氮-1-[4-(1-甲基比嗤-4-基)苯基胺基罗炭基]_ 6_(4_甲基六氮比σ井-1_基ϋ朵， 經濟部智慧財產局員工消費合作社印製 5-氯-2,3_二氮-1-[4’-亂基-3’-甲基聯苯基-4-胺基魏基]_ 6_(4_甲基六氮11比喷-1-基)-111_弓卜朵， 5-&gt;臭-2,3-二氮-1_[4*-亂基-3’-曱基聯苯基-4-胺基戴基]_ 6_(4_甲基六風σ比〇井_1_基)_1Η_口引σ朵’ 5-氯-2,3-二氮_1-[4_(2_甲基11比唆-5-基)苯基胺基援基]_ 150 本紙張尺度適用中國國家標準（CNS ) Α4規格（2iOX297公釐） 509687 A8 B8 C8 D8 申請專利範圍 經濟部智慧財產局員工消費合作社印製 6一(4-甲基六氫吼口井-1-基)-1Ηι%， 5善2,3_二氫小[4-(2-甲基η比啤j基)苯基胺基羰基卜 6-(4-甲基六氫〇比_-1·基卜&amp;， 5-氣·2,3-二氫小|&gt;(3-甲基义2冬号二峻冬基)茶小基 胺基戴基]各(4-甲基六氫吼啩七基朵， 2.3- —A-5-f -1-基胺基幾基]-6-(4·甲基六氣咄畊基)-1H_，呼， 5-溴-2,3_ 二氫-1·[5_(3·甲基 胺基幾基]各(4_甲基六氫°比啡七基)_1H_^#， 5-氯-2,3二氫·1-[5-(5-甲基气唾_2_基)茶基胺基幾 基]-6_(4·甲基六氫吡畊小基)、旧_令朵， 2.3- 二氫-5-甲氧基-ΗΗ5-甲基号哇:2基)革+▲胺 基幾基]各(4-甲基六氫吼畊七基Μη_♦朵:、5-演-2,3-二氫-1-[3-甲基-4切咬_2_基)苯基胺墓藏 基]_6-(4_甲基六氫吡啡-1-基朵， -- ^’3-二氫-5-曱氧基-1_[3-甲基喷咬_2_基)苯基胺基 羰基]_6_(4_曱基六氫°比畊小基)_出_令朵， 5-氯·2,3_二氫-6-(4-甲基六氫咄啡+基^办甲基 哺唆-2-基)苯基胺基獄基]，5|2’3-二氫_1:[3-甲基-4相私基）苯基胺基叛 基]-6_(4-甲基六虱咐^井_1_基)，5H3·二氫-1·[3-甲基-4·(’仏基）苯基胺基数 基]_6-(4-曱基六氫吡畊-1-基，2’3_二氫-5-曱氧基-1·[3·甲基·4相料基)苯基胺基 -4- (請先閱讀背面之注意事項再填寫本頁) -裝」 、言. .加 151 509687 A8 B8 C8 D8 穴、申請專利範圍 夢炭基]-6-(4-甲基六鼠基引11 朵， (請先閱讀背面之注意事項再填寫本頁) 5_溴_2,3-二氫小[4-(2,6-二甲基吡啶-4-基)-3-甲基苯 基胺基讓基]-6-(4-甲基六鼠σ比11井-1-基卜朵’ 2.3- 二鼠-5_曱氧基-l-[4-(2,6-二甲基。比唆_4-基)-3-甲 基苯基胺基羰基]-6-(4-甲基六氫咐畊-1-基)-1H-吲 口朵， 5-氣-2,3-二鼠-l-[5-(2,6-二甲基°比唆_4-基）茶-1-基胺 基羰基]-6-(4-甲基六氫吡畊小基)-1H-吲哚， 5-》臭-2,3-二鼠-1_[5-(2,6-二甲基。比°定_4-基）秦-1-基胺 基&gt;炭基]-6-(4-甲基六氮°比。井-1-基)-1Η-弓卜朵’ 2.3- 二氫小[5-(2,6_二甲基吡啶-4-基）萘小基胺基羰 基]_6-(4•甲基六氣p比啡-1·基σ朵， 2.3- 二氳-1-[4-(2,6-二甲基吡啶-3-基)-3-甲基苯基胺基 _炭基]-5-甲氧基-6-(4-甲基六鼠ϋ比ϋ井-1·基朵’ 5-&gt;臭-2,3-二氮-l-[3-甲基坐-2-基）苯基胺基#炭 基]-6_(4-甲基六氮11比11 井-1-基)-1Η-^11 朵， 5-氣-2,3-二氮-1-[3-曱基-4-(嗔嗤-2-基）苯基胺基爹炭 基]-6-(4-甲基六風峨11 井-1-基)-lH-pf卜朵， 經濟部智慧財產局員工消費合作社印製 2.3- 二鼠-5-甲氧基-l-[3-甲基-4-(嗔°坐-2-基)苯基胺基 夢炭基]-6-(4-甲基六氮ϋ比11 井-1-基)-111-0引ϋ朵， 1-(5-乙酿基蒸-1-基胺基幾基)-5-氣_2,3_二鼠-6-(4-甲 基六氫吡畊小基)-1Η-吲哚， 5-氮-2,3-二鼠-6-(4-曱基六氮吼0井-1-基)-1-[5-(嘴咬-2_ 基氧基)萘小基胺基羰基]_1H-吲哚， 152 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 509687 A8 B8 C8 D8 7T、申請專利範圍 (請先閱讀背面之注意事項再填寫本頁) 5-氣-2,3-二鼠-6-(4-甲基六風11比11井-1-基)-1-[5-(癌°定-5-基)秦-1&quot;·基胺基Μ基]_1H-叫卜朵^ 2,3-二鼠-5-甲氧基-6-(4-甲基六氮。比併-1-基)-1-[5-(嘴 唆-5-基)茶_1-基胺基幾基]-1H-S丨1^ ’ 5-氯-1-(5-鼠基茶-1_基胺基幾基)-2,3-二氮-6-(4-甲基 六鼠11比啡-1-基)-1Η·Ί卜朵’ 5-氣-2,3-二氫小[5-(5-甲基-1，2,4-啐二唑-3·基)萘小基 胺基魏基]-6-(4-甲基六氮11比哎-1-基)-1Η-^ 〇朵 或其醫藥上可接受鹽類。 9. 一種製備根據申請專利範圍第1項之式(Γ)化合物或 其醫藥上可接受鹽類的方法，其包含： ‘ -ί ⑻若其中γ為ΝΗ，則將式(II)化合物： Ra-NC(=0) (II) 其中Ra係如申請專利範圍第1項式(Γ)化合物所定義 或其受保護衍生物，與式(ΙΠ)化合物偶合， 'Where Ra is a group r1Y7v-&quot; ΐ? Ιπ (R) a (i) with the formula (i) where: P1 is phenyl, naphthyl, fluorenyl, or tetraisoisophosphonyl; R1 and R2 Are each independently hydrogen, halogen, CK6 alkyl, cyano or Cp6 alkoxycarbonylamino; a is 1 or 2; or Ra is a group of formula (ii) 7) Zo, 丨. 装 #. ~. (Please read the notes on the back before filling out this page) (ϋ) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, where P2 and P3 are independently phenyl, naphthyl, thienyl, furyl, imidazolyl,噚 Junki, 嗤, 嗔, 嗔, 喝, 喝, 癌, 癌, 癌, 癌, 癌, 嗒, 嗒, 吡, 吡, 吡, 吡, 吡 基, 林, 林, 林, 林, 林, 林Heterogeneous basis; 140 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 509687 ABCD ττ, apply for patents (please read the precautions on the back before filling this page) Α is a bond or Oxygen, -CHrCH2-, or NR4, where R4 is hydrogen or C ^ 6 alkyl; R1, R2, and R3 are each independently fluorene, halogen, CK6 alkyl, Cy alkyl, or cyano; Y is -NH- Or -CH2 -; W is -CHCH- or-(CH2) r, where t is 2 or 3; Rb is hydrogen, halogen, CV6 alkyl, trifluoromethyl, € 6 alkoxy, or C2_6 alkenyl; Re is Rhenium or CU6 alkyl. 2. The compound of formula (Γ) according to item 1 of the scope of patent application, wherein R1 is a halogen atom. 3. The compound of formula (Γ) according to item 1 or 2 of the scope of patent application, wherein R2 and / or R3 are each hydrogen, halogen, or CK6 alkyl. 4. The compound of formula (Γ) according to item 1 or 2 of the scope of patent application, wherein P1 and P2 are benzyl, naphthyl or fluorenyl. 5. The compound of formula (Γ) according to item 1 or 2 of the scope of the patent application, wherein Y is -NH-. 6. The compound of formula (Γ) according to item 1 or 2 of the scope of the patent application, wherein W is a group of formula-(CH2) 2 •. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 7. According to the formula (Γ) of the first or second item of the scope of patent application, where 圮 is a heart ^ alkoxy group. 8. The compound of formula (Γ) according to item 1 of the scope of patent application, which is: 1-[(4-bromo-3_tolyl) aminocarbonyl] -5-methoxy-6- (4-methyl Hexahydropyridin-1-yl) -m-indole, 141 This paper size applies to the Chinese National Standard (CNS) A4 (210 X 297 mm) 509687 A8 B8 C8 D8 TC, patent application drywall (please read first Note on the back, please fill in this page again) l-[(4-Bromo-tolyl) aminocarbonyl] -2,3-dihydro-5-fluorenyloxy-6- (4-methylhexazine. Than ϋ Well-1-yl 5 1-[(2,3-dichlorophenyl) amino green] -2,3-diaza-5-methoxy-6- (4-methylhexaazapine ratio 11 I-1-yl) -111-5111, 2.3-dimur-5-yloxy-6- (4-fluorenylhexamidine-1-yl) -144- (13pyridin-4-yl ) Naphthalen-1-ylaminocarbonyl] -1H-indole, 2.3-difluoren-5-methoxy-6- (4-methylhexahydropyridyl) -1- [5- (pyridine- 4-yl) naphthalene-1ylaminocarbonyl] 1H-indole, 1-[(2,3-digas-4- (11 to 11 amidin-4-yl) phenylaminoquinoyl] -2, 3_dimur-5-methoxy-6- (4-methylhexahydropyridin-1-yl) -1H-indole, 2.3-diaza-5-methoxy-6- (4-methyl Hexyloxybenzyl-1-Hydroxy-1-yl) -l- (tIquinazine-5-ylaminocarbonyl) -1Η- Indole, 2.3-diaza-6- (4-methylhexazine ratio 1 ^ · 1-yl) -1- [4- (meta-o--4-yl) naphthalen-1-ylaminocarbonyl) _1Η -Indole, 5-chloro-2,3_diazine-6- (4-methylhexaazine 11 to σwell-1-yl) -1- [4- (° to fluoren-4-yl) naphthalene- 1-ylaminocarbonyl) -1 oxindole, 5 earning> stinky_2,3_dimur_6 雠 (4_fluorenylhexarat mouth than koujing-1_yl) _1hetero [4- ( Mouth-to-mouth _4-based) steamed-1-ylamino-based weiji) -1Η-Ί 卜 朵 'Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -(4-Methylhexanox-1-well-1-yl) -1_ [4- (σSpecific-4-yl) phenylaminocarbonyl] -m-indole, 5- &gt; [3-Ga-4- (11bifluoren-4-yl) phenylaminoweiyl] _2,3-dimur-6- (4-methylhexahydropyridin-1-yl) -1fluorene Indole, 2.3-diaza-5-methyl-6- (4-methylhexamorine. Bispherin-1-yl) -1- [4- (σ ratio 唆 -4-yl) fluoren-1-ylamine Carbonyl group] _1Η-indole, 142 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 刈 9687 A8 B8 C8 ------- -----D8 — ........................................... ............................. ................................................... ...........-.............. 6. Application for patent scope H3_chloroice (pyridine-4 -Yl) phenylaminocarbonyl] -2,3_dihydro | methyl-6_ (4-methylhexahydropyridine) -iH-indole, 2.3-dihydro-6_ (4-methylhexa Pycnogenol small) small [4- (pyridinyl) naphthylaminocarbonyl] -5_vinyl-1H-indole, 2,3 · monoazine-5-ethyl-6- (4-methyl Hexahydrazone ratio 17 wells-1 • yl) -1- [4- (σ ratio! 1-Analyl) naphthalen-1-ylaminocarbonyl] -1 Η-indole, 冬 3-chlorodong (amidin-4 -Yl) phenylaminocarbonyl] -2,3-dihydro-5_ethyl-6- (4-methylhexahydropyridine small group) -fluorene_indole, 2.3-one mouse-6- ( 4-methylhexahydro "than sigma-1-yl) _1- [4- (snake" 4-yl) naphthalene-1-ylaminocarbonyl] -5_trifluoromethyl-1fluorene-indole, 1_ [3-Chloro-4- (pyridin-4-yl) phenylaminocarbonyl] -2,3-dihydro-6- (4-methylhexahydropyridine · 1-yl) -5-trifluoromethyl 1H-indole, 2.3-dihydro-5-methoxy-6- (4-methylhexahydropyridin-1-yl) small [4- (pyridinyl) naphthylethenyl]- 1H-indole :: 2.3 --- murine-5_methoxy-6_ (4-methylhexaazine σ-biffin-1-ylpyridin-4-yl) -naphthalene-1_ylethyl Group;] _ ιη_indole, 2,3_dihydro-6- (4-methylhexahydropyridin-1-yl) _1- [4_ (pyridin-4-yl) naphthalen-1-ylethylfluorenyl ] -1Η-Indole, 5-qiyifeng-6- (4-methylhexazine Mouth-well-1-yl) -1 «&quot; [4- (Mouth-bite-4 ·» yl) naphthalene -1-ylethylfluorenyl] -1fluorene-indiolide, 5-bromo-2,3-dihydro-6- (4-methylhexahydrogenated-1-yl) small [4 · ( -Yl) naphthyl small ethynyl] pyridine, 2.3-dihydro-6- (4-methylhexahydropyridin-1-yl) small [4- (pyridin-4-yl) naphthyl small ethynyl ] 5 sides vinyl-1H-, mouth flower, 143 This paper size applies the Zhongguanjia Standard (CNS) A4 · (21GX297 mm) '~~ II— Order Aw (Please read the precautions on the back before filling (This page) The scope of patent application A8 Β8 C8 D8 5-Bromo-2,3-dihydro_6- (l-methylhexahydropyridine-4-yl) -1- [4- (Pyridin-4-yl) naphthalen-1-ylaminoweiyl] -1H-gumbudol, 5-chloro-2,3-dihydro-6- (4-methylhexahydropyridine Yl) small [5- (pyridin-4-yl) naphthalene-1-ylaminocarbonyl] -1Η-indole, 5-bromo-2,3-dihydro-6- (4-methylhexahydropyridine Small group) small [5- (pyridin-4-yl) naphthalene small group aminocarbonyl HH-indole, 2. 3-Dimur-5-5-fluorenyloxy-6- (4 • fluorenylhexahydroσσ is smaller than σ-1-1-Kylin-6-ylaminocarbonyl) -1fluorene-indole, 2.3-dihydrogen is smaller [4 -(Third-butoxycarbonylamino) phenylaminocarbonyl] -5-chloro-6- (4-methylhexahydropyridine_1-yl) -1Η-indole, 5-bromo_2 , 3-dihydro-6_ (4-fluorenylhexahydropyridine small) small (fluorin-6-ylaminocarbonyl) -1fluorene-indole, 6-bromo-7_ (4-fluorenylhexahydropyridine口 井 小 基) -1_ [4- (suddin-4-yl) naphthyl small aminoaminocarbonyl] -1,2,3,4 · tetrahydrofluoroline, 5_gas-2,3-diwind- 6- (4-methylhexazine 11-well-1-yl) -1_ (4-phenoxyphenylphenylaminocarbonyl) -1Η-indole, 5-fluoro_2,3-diazine-1- (4- (4-Gaphenoxy) phenylamino group) -6- (4-methylhexahydropyridine) -1H-indole, 5-chloro-2,3-dihydro each ( 4-methylhexahydropyridine) small (fluoren-6-ylaminocarbonyl) -1fluorene-indole, 5-chloro-2,3-difluorene · 6 · (4-methylhexahydrocarbyl) Ghen-1-yl) · 1- (3-benzyloxyphenylaminocarbonyl) -1Η-indole, 5-Gas-2,3-diazine-6- (4-methylhexazine σ ratio 11 wells -1-yl) -1- [4- (bite-2 · * yl) phenylaminocarbonyl] -1Η-indole, 144 This paper size applies to China National Standard (CNS) A4 (210 X 297) (%) (Please read the notes on the back before filling this page) L r • 1— »509687 A8 B8 C8 D8 6. Scope of patent application (please read the notes on the back before filling this page) 1- (3-benzyl Oxyphenylaminocarbonyl) -5-gas-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1Η-indole, 1-(4-benzyloxy Phenylaminocarbonyl) -5-chloro-2,3-difluorene-6- (4-methylhexahydropyrine-1-yl) -1fluorene-indole, 5-chloro-2,3-di Murine-6- (4-methylhexamurine 11-degree well_1-yl) -1- (2-methyl oral quinolin-6-ylaminocarbonyl) -m-indole, 5-chloro-2 , 3-diazol-1- [4- (anan-2-yl) phenylaminoquinoyl] -6- (4-methylhexazine 11-well-1-yl) -1Η-Gongbuduo '· 5-Gas-2,3-dimur-6- (4-fluorenylhexamur ° Biffin-1_yl) -1- [4- (pyridin-2-yl) phenylaminocarbonyl] -1H-indole, 5-Ga-2,3-dimur-6- (4-methylhexamur ^^-1-yl) -1-0- (11 specific sulfan-4-yl) diethyl Fermentation group] -1H- is called 丨 σ 朵 '5- &gt; Stink-2,3-dirat-6- (4-methylhexadidine-4_yl) steam-1-ylethynyl] -lH- The p's bow system is a ratio of 5-qi-2,3-diazamethylhexazane 11. Well-4-yl) Tetra-1-based kijiki] -6- (4-methylhexaazine 11 to 11 well_1_yl) -1Η_ 弓 丨 1 ^ '5-Ga-2,3 · Dihydro small [4- (2-methyloxazol-4-yl) phenylaminocarbonyl]-6- (4-methylhexarmouth than Mizuki-1-yl) -1Η-ρ Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs of the People's Republic of China Methylpyridin-4-yl) phenylamino-carbonyl] -1Η-indole, 5-chloro-2,3-diazine-6- (4-methylhexafluorosigma-1_yl)- 1- [4- (2-methylpyridin-4-yl) phenylaminocarbonyl] -1Η-indole, 5-chloro_2,3 · difluorene-1 · [4_ (2,6-dimethyl Pyridin-4-yl) phenylaminocarbonyl] -6- (4-methylhexahydropyridin_1-yl) -1Η-indole, 145 This paper is sized to the Chinese National Standard (CNS) A4 specification ( 2i0X297 mm) V7VJ〇 / A8 B8 C8 --- ~ _D8., Patent application scope odor- · 2,3-dihydro-l- [4- (2,6_dimethyl ratio. Set "4- Phenyl) phenylaminocarbamoyl; h6- (4-fluorenylhexamethylpyridin-1-yl) -1fluorene-indole, 2,3-dihydro small [4- (2,6-dimethyl Pyridinyl) phenylaminocarbonyl) -5methylamino-6- (4-methylhexamuryl) -1 . Flower, 5′-2,3-dihydro-1_ [4- (2,6_dimethylpyridine_3_yl) phenylaminocarbonyl] «4-methylhexahydropyridin-1-yl) -1Η-indole, bromo_2,3_dihydro small [4_ (2,6_dipyridylpyridyl) phenylaminocarbonyl &gt; 6- (4-methylhexahydropyridine-1- ) -1Η-indole, 2 oligo-l- [4- (2,6-dimethylpyridin-3-yl) phenylaminocarbonyl] -5_methylamino-6- (4-methyl The base six rat 11 is more than a well -1-yl) -1 Η-called Bu Duo, 5-qi-2,3-diaza-6- (4-methylhexaazine 11 than -1 -yl) -1- [4- (5-methyl_1,2,4_fluorenediazol-3-yl) phenylaminocarbonyl] -1fluorene-indole, 5-lacto-2,3-dihydro-1- [4 -(3-methyl_1,2,4-oxadiazin-5-yl) phenylaminocarbonyl] -6- (4-methylhexahydropyridin-1-yl) -1Η-indole, 5-chloro-2,3-dihydro-6- (4-methylhexahydropyridine-1.yl) -1- [3- (pyrimidin 4-yloxy) phenylaminocarbonyl] _1H-indole , 5-Gas-2,3-diazine-6- (4-methylhexaazine σ ratio 11 well-1-yl) -1- {4 «N_methyl_N- (pyrimidin-2-yl) Amine] phenylaminocarbonyl} -1Η-indole, 5- &gt; Oxyl-2,3-diaza-1_ [4- (anan-2-yl) phenylamino # carbonyl] -6 -(4-methylhexaazine 11 to 13 well-1-yl) -1Η-Gongbuduo '5-chloro_2,3-dihydro-6- (4-methylhexahydropyridine Phen-1-yl) small [4- (thien-3-yl) phenylaminoyl] -1H-1 budol '5-bromo_2,3-dihydro-6- (4-methylhexa Hydropyridine small group) -1_ [4_ (thiazole_2_yl) phenylaminocarbonyl] · 1 吲 -indole, 146 This paper size applies to China National Standard (CNS) A4 size (210 X 297 mm) (please Read the precautions on the back before filling out this page)-Order 509687 ABCD printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 6. Scope of patent application (please read the precautions on the back before filling out this page) 5- 气 -2,3 -Dihydro-6- (4-methylhexahydropyridine-1-yl) small [4- (thiazol-2-yl) phenylaminofluorenyl] -1H-5BUDO '1- [4 -(5-Ethylthiophen-2-yl) phenylaminocarbonyl] -5-chloro-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1H- Indole, 1- (5- "Binamin-1_ylethynyl) -5 -chloro-2,3-diazepine-6- (4-methylhexaazepine-1-yl) -1Η- Indole, 5-chloro-2,3-dimur-6- (4-methylhexamur 1 ^ Sakai-1 -yl) -1- (8-phenylphosphonium-5-ylaminocarbonyl ] -1Η-Indole, 5- &gt; Odor-2,3-Digas-6_ (4-methylhexaazine 11 to 11 well-1-yl) -1- (8-phenyl0quinoline-5 -Aminoaminocarbonyl] -1H · indole, 5-chloro_2,3-di Hydrogen-6- (4-methylhexapyridin-1-yl) small [2- (2 · phenylethyl) pyridin-6-ylaminocarbonyl] -1H-indole, 5-chloro- 2,3-Dimur-6- (4-methylhexaramine. I-1-yl) -1- [5- (1-fluorenylhexahydropyridinyl) naphthalene-1-ylaminocarbonyl] _m-indole, 5-mo-2,3-diaza-1 -[4- (Isomalin-4-yl) phenylaminoamino] -6- (4-methylhexaazol-1-yl) _1Η-0, 5 · qi-2,3 -Diazepine-1_ [4_ (Isopyridin-4_yl) phenylaminoamino] -6_ (4_methylhexaazine 11-well-1-yl) -1Η- &lt; σ flower, Ministry of Economic Affairs wisdom 5-Bromo-2,3-dihydro-6- (4-methylhexahydropyrine-1-yl) -1_ [4- (fluoren-3-yl) phenylamine Carbonyl] -1Η-indole, 5-chloro-2,3-dihydro-6- (4-methylhexahydropyridin-1-yl) -1- [4- (fluorin-3-yl) Phenylaminocarbonyl] -1Η-indole, 5-chloro_2,3_diwind-6- (4_methylhexamuridine ratioσwell-1-yl) -1_ [2-methyl ~ 1 ， 2,3,4-tetrahydroisofluorolin-7-yl) aminocarbonyl] -1Η · indole, 147 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 509687 ABCD Economy Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Education. Scope of patent application 5-Bromo-2,3-dihydro-6- (4-methylhexahydropyridine-1 -yl) _ 1-[2-methyl- 1,2,3,4-tetrahydroisofluoren-7-yl) aminocarbonyl] -1H-indole, 5- &gt; Smell-2,3 --- Wind-6- (4-methylhexaazine. Let's talk about -1-yl) -1- [4- (bit. Lin-8-yl) phenylaminocarbonylfluorene-indole, 5-qi- 2,3-^-nitro-6- (4-fluorenylhexazolium ratio® well-1-yl) -1- [4- (HA-8-yl) phenylaminocarbonyl] -1Η · ind Indole, 5-Gas-2,3-Difluorene-small [4- (imidyl-1-yl) phenylamino] -yl] -6- (4-methylhexahydropyridin-1-yl) _1H-ind Indole, 5-qi-2,3-dimur-6_ (4-fluorenylhexafluoro 17 to 1 ^ well_1_yl) -1- [4- (σ than bit-4-yl) phenylamino Carbonyl] -1Η-indole, 2.3-diazine-5-methoxy-6- (4-methylhexazine 1 ^ ratio 11 well-1-Thai) -1-[(8-phenylfluorene- 5-yl) aminocarbonyl] -1H-indole, 5-gas-2,3-dihydro-6- (4-methylhexahydropyridine) small [(8-phenylphosphonium ) Aminocarbonyl] _111_indole, 5-bromo-2,3-dihydro (4-methylhexahydropyridin-1-yl) _1-[(8_phenylfluorin-4-yl) Aminocarbonyl] _1H-indole, 2.3-dihydro-5_methoxy-6- (4-methylhexahydro σ ratio 11 well-1-yl) -1-[(8-phenylphosphonium- 4-yl) aminocarbonyl] -1H-indole, 5-chloro-2,3-dihydro small [4- (2,6-Difluorenyl-hexamethylpyrrolyl) each methylbenzylamine Carbonyl] dong (4-methylhexahydropyridin-1-yl) -1Η-indole, 5 · Ga-2,3-di -1- [3-Methyl-4- (6-methylpyridin-2-yl) phenylaminoquinyl] -6- (4-methylhexahydro5-bromo_2,3_dihydro small [3-Methyl-4- (6-methylpyridin-2_yl) phenylamine 148 This paper is scaled to the standard (CNS) Α4 · / (210X297) (Please read the precautions on the back before filling in this (Page) 509687 A8 B8 C8 D8 VI. Application for patent scope Chikiji] -6- (4-methylhexaazine ° well_1_yl) -1Η_1 | ϋ 朵》 2.3- Dihydro-5-methoxy Small [3-methylpyridine (6-methylpyridin-2-yl) phenylaminocarbonyl] -6- (4-methylhexahydropyridine small hydrazone-indole, 5-chloro-2,3 -Dihydro small [5- (6-methylpyridin-2-yl) naphthalene small amine amino group] -6- (4-fluorenylhexahydrocohen-1-yl) -1H-indole, 2.3- Dihydro-5-methoxy-1- [5- (6-methylpyridin-2-yl) naphthylaminoaminocarbonyl] -6- (4-methylhexahydropyridine) -1Η -Indole, 5-gas_2,3_dimur-6- (4-ethylhexaaza. ratio. Well-1-yl) -1- [4- (σ to σ amidyl) naphthalene small group aminocarbonyl hydrazone-indole, 5-gas · 2,3_digas-6- (4-ethylhexazine σ well-1-yl) _ι_ [5- (ιι ratio. fixed_4_yl) naphthalen-1-ylaminocarbonyl] -1Η-indole, S-gas_2,3 · dihydro_6_ (hexahydro 00 Well-1 · yl) -l- [4- (u than ice group) steam · 1-ylaminocarbonyl] _1H-indole hydrochloride, 5-chloro-2,3-dihydro-6 -(Hexahydro-1-yl) -small [5- (Hydroxy-4-yl) naphthyl-1-ylaminocarbonyl] -1Η-indole hydrochloride,-5-Gas-2,3 -Dihydro-6- (4-methylhexahydro. Than σ-well 4-yl) -1- [4decaphen-3-yl) phenylaminocarbonyl] -1Η-indole, 5-bromo- 2,3_dihydro-6- (4-methylhexahydropyridine small group) small [4- (Dahu-1-3-yl) phenylaminocarbonyl] -1Η-indole, 5-chloro_2, 3-dihydro-6_ (4_fluorenylhexahydropyridin_1_yl) -1_ [winter (pyridine: _2_yl) phenylaminocarbonyl] -1Η-indole, 5-bromo-2,3 -Dihydro-6- (4-methylhexahydrocarbyl-1-yl) -1- [4- (σ ratioσwell_2_yl) phenylaminocarbonylfluorene-indole, 5-gas-2 , 3-Dihydro_6_ (4_methylhexahydro σ ratio σ well small base) -1 _ [(2_phenyl hydrazine 149 This paper size applies to China National Standard (CNS) Α4 specifications (210X297 public envy) a- ^ -------- (Please (Please read the notes on the back before filling out this page)-! &Lt; »· L ·. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 509687 A8 B8 C8 D8 6. Application for Patent Range Pyridin-5-yl) aminocarbonyl ] _1Η-indole, (Please read the precautions on the back before filling out this page) 5- &gt; Smelt-2,3-digas-6- (4-methylhexaramine 11-well-1-yl)- 1-[(2-phenyl1: | specifically-5-yl) aminodynyl] -1H-fluorene. ^^ 5-Chloro-2,3-dimur-l- [4- (6-methylσ 荅 pent-3-yl) phenylamino green] -6- (4-fluorenylhexahydropyridine -1-yl) -1fluorene-indole, 5- &gt; odor-2,3-diaza-l- [4- (6-methyl tower.well-3-yl) phenylaminofluorenyl] _ 6- (4-methylhexazine ratio than 11-well-1-yl) _1Η-0 lead sigma, 5-chloro-2,3-diazine-6- (4-methylhexazine 0-well-0- 1-yl) -1- [4- (〇 比 0 定 -3-yl) phenylaminocarbonyl] 1H-indole, 5-chloro-2,3-dihydro-l- [4- (5- Methyloxazol-2-yl) phenylaminocarbonyl] -6- (4-methylhexazine. 11-1-1-yl) -111-1? 1 '2,3-diaza- 5-Methoxy-1- [4- (5 • fluorenylσ-thio-2-yl) phenylaminocarbonyl] -6- (4-methylhexahydropyridin-1-yl) -1fluorene-indole Indole, 5-bromo-2,3-dihydro_1- [4- (5 • methyloxazol-2-yl) phenylaminocarbonyl] · 6- (4-methylhexazine-1 _Yl) _1Η-gongbuduo '5-chloro-2,3-diazol-1- [4- (1-methyl. Than ° -4-yl) phenylamino group] _ 6- ( 4-methylhexahydropyridine) -m-indole, 5- &gt; odor-2,3-diazol-1- [4- (1-methylpyridin-4-yl) phenylamine Kelow Carbon-Based] _ 6_ (4_methylhexanitrogen ratio σwell-1_ Jieduoduo, printed by Employee Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs 5-Chloro-2,3_diazol-1- [4'-anthyl-3'-methylbiphenyl-4-aminoweiyl] _ 6_ (4_methylhexazine 11 ratio spray-1 -Yl) -111_Gongbuduo, 5- &gt; odor-2,3-diaza-1_ [4 * -ranyl-3'-fluorenylbiphenyl-4-aminodynyl] _ 6_ ( 4-methylhexafluoroσ ratio 〇well_1_yl) _1Η_ 口 引 引 σ 朵 '5-chloro-2,3-diazine_1- [4_ (2_methyl11 ratio 唆 -5-yl) Phenylamino group] _ 150 This paper size applies to Chinese National Standard (CNS) A4 specification (2iOX297 mm) 509687 A8 B8 C8 D8 Patent application scope Intellectual Property Bureau of the Ministry of Economic Affairs Employee Cooperative Cooperative printed 6-1 (4-A Hexahydro-Houkou-1-yl) -1%, 5% 2,3-dihydrogen is smaller [4- (2-methylη is smaller than beer jyl) phenylaminocarbonyl group 6- (4-methyl Hexahydrogen is smaller than -1-Kibb &amp;, 5-Ga · 2,3-dihydro is smaller | &gt; (3-methylsynthesis 2 Donghao Dijundongyl) tea small amine aminodaiky] Each (4-methylhexahydrohexanosyl, 2.3- —A-5-f -1-ylaminoquinoyl) -6- (4-methylhexakistilbenzyl) -1H—, 5-bromo-2,3_dihydro-1 · [5_ (3 · methylaminoquinoyl) each (4-methylhexahydro ° biffinyl heptyl) _1H _ ^ #, 5-chloro-2,3 Hydrogen · 1- [5- (5-methyl arsino_2_yl) theylaminoamino]- 6_ (4-methylhexahydropyridine small group), old_lingduo, 2.3-dihydro-5-methoxy-fluorenyl-5-methyl number: 2 groups) leather + ▲ amino group) each ( 4-MethylHexahydrogenyl Hexyl Mη_ ♦ :: 5-5--2-2,3-dihydro-1- [3-methyl-4 cut bit_2_yl) phenylamine tomb group] _6 -(4-methylhexahydropyridin-1-yldo,-^ '3-dihydro-5-fluorenyloxy-1_ [3-methylpentane-2-yl) phenylaminocarbonyl] _6_ (4_Hexyl hexahydro ° specific farming small base) _ 出 _ 令 朵, 5-chloro · 2,3_dihydro-6- (4-methylhexahydrophenanthrene + radical ^ methyl methyl -2-yl) phenylaminobenzyl], 5 | 2'3-dihydro_1: [3-methyl-4phasyl) phenylaminobenzyl] -6_ (4-methylhexa Lice asked ^ well_1_ group), 5H3 · dihydro-1 · [3-methyl-4 · ('fluorenyl) phenylamino group] _6- (4-fluorenylhexahydropyridine-1- Radical, 2'3_dihydro-5-fluorenyloxy-1 · [3 · methyl · 4-phase material) phenylamino-4- (Please read the precautions on the back before filling this page) -pack ", Add ... add 151 509687 A8 B8 C8 D8 points, patent application scope dream carbon-based] -6- (4-methylhexamuryl 11 lead, (Please read the precautions on the back before filling this page) 5 _Bromo_2,3-dihydro small [4- (2,6-dimethylpyridine -4-yl) -3-methylphenylamino phenyl group] -6- (4-methylhexamoor σ than 11 wells -1-ylbudol '2.3- dimur-5_fluorenoxy-1 -[4- (2,6-dimethyl. Than _4-yl) -3-methylphenylaminocarbonyl] -6- (4-methylhexahydrocarbyl-1-yl) -1H-indole, 5-Ga-2,3- Dimur-l- [5- (2,6-dimethyl ° ratio 唆 _4-yl) tea-1-ylaminocarbonyl] -6- (4-methylhexahydropyridine) -1H -Indole, 5- "smell-2,3-dimurine-1_ [5- (2,6-dimethyl. Ratio_4-yl) cin-1-ylamino &gt; carbon-based]- 6- (4-methylhexanitrogen ° ratio. Well-1-yl) -1Η-Gongbuduo '2.3-dihydro small [5- (2,6-dimethylpyridin-4-yl) naphthalene small group Aminocarbonyl] -6- (4 • methylhexaqi p-biffin-1 · yl sigma, 2.3-difluorene-1- [4- (2,6-dimethylpyridin-3-yl) -3- Methylphenylamino_carbonyl] -5-methoxy-6- (4-methylhexamolybidine than Sakai-1 · Gido '5- &gt; odor-2,3-diaza-1 -[3-methylbenzo-2-yl) phenylamino #carbonyl] -6_ (4-methylhexaazine 11 to 11 well-1-yl) -1Η- ^ 11 , 3-Diazol-1- [3-fluorenyl-4- (fluoren-2-yl) phenylaminopyridyl] -6- (4-methylhexafene 11-yl-1-yl) -lH-pf Budu, printed by 2.3-Dirat-5-methoxy-l- [3-methyl-4- (嗔 ° -2-yl) phenylamine Base dream carbon-based] -6- (4-methylhexaazepine ratio 11 well-1-yl ) -111-0 Induction, 1- (5-Ethyl-steamed-1-ylaminojiki) -5-qi_2,3_dirat-6- (4-methylhexahydropyridine (Small group) -1A-indole, 5-nitro-2,3-dimur-6- (4-fluorenylhexazine-0-well-1-yl) -1- [5- (mouth bite-2_yloxy ) Naphthalene small amine aminocarbonyl] _1H-indole, 152 This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 509687 A8 B8 C8 D8 7T, patent application scope (please read the back page first Please fill out this page again) 5-Gas-2,3-Dirat-6- (4-methylhexawind 11 to 11-well-1-yl) -1- [5- (Cancer ° D-5-yl ) Qin-1 &quot; · aminoamino M group] _1H- is called Budu ^ 2,3-dimur-5-methoxy-6- (4-methylhexaaza.pyridin-1-yl) -1 -[5- (mouth 唆 -5-yl) cha_1-ylaminoquinyl] -1H-S 丨 1 ^ '5-chloro-1- (5-muryl tea-1_ylaminoquinyl ) -2,3-diazepine-6- (4-methylhexarat 11-pyridin-1-yl) -1Η · Ί 卜 朵 '5-qi-2,3-dihydro small [5- (5- Methyl-1,2,4-fluorenediazole-3.yl) naphthalene small aminoaminoweiyl] -6- (4-methylhexaazine 11 ratio 1-1-yl) -1Η- ^ 〇 or Its pharmaceutically acceptable salts. 9. A method for preparing a compound of formula (Γ) or a pharmaceutically acceptable salt thereof according to item 1 of the scope of the patent application, comprising:--⑻ If γ is NΗ, the compound of formula (II): Ra -NC (= 0) (II) where Ra is as defined by the compound of formula (Γ) or protected derivative thereof, which is coupled with the compound of formula (ΙΠ), 經濟部智慧財產局員工消費合作社印製 其中W、Rb和Re係如申請專利範圍第1項式(Γ)化合 物所定義，或其受保護之衍生物； 或 (b)若其中Y為NH，則將式(IV)化合物 153 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 1申請專 利範圍 r、nh2 (c)將式㈣齡尿切成劑反應；R、y_(c 哪 l2 (V) y Ra係如nt翻難帛1項切,)化合物所定 為-CH2·和1?為_素原子，與式则化合物反應 且之後，視需要： • 移除任何保護基， •轉換式(I1)化合物成其他之式(I，)化合物， •形成醫藥上可接受鹽類。 根據申請專利範圍第1項之式(1，)化合物，其係用於 治療CNS病症。 11· 一種具有5HT1A/1B/1D受體拮抗劑活性之醫藥組合 物，其包含根據申請專利範圍第1項之式(Γ)化合物， 以及醫藥上可接受之載體。 (請先閱讀背面之注意事項再填寫本頁) ί.Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, where W, Rb and Re are as defined by the compound of formula (Γ) in the scope of the patent application, or their protected derivatives; or (b) if Y is NH, The compound of formula (IV) 153 is applied to the paper size of Chinese National Standard (CNS) A4 (210X297 mm). 1 Scope of patent application r, nh2 (c) Reaction of formula diarrhea urine; R, y_ (c Which l2 (V) y Ra is the same as nt, and the compound is defined as -CH2 · and 1? Are _ prime atoms, which react with the compound of formula and then, if necessary: • remove any protecting groups, • Conversion of compounds of formula (I1) into other compounds of formula (I,), • Formation of pharmaceutically acceptable salts. A compound of formula (1,) according to item 1 of the scope of patent application, which is used for treating CNS disorders. 11. A pharmaceutical composition having 5HT1A / 1B / 1D receptor antagonist activity, comprising a compound of formula (Γ) according to item 1 of the scope of patent application, and a pharmaceutically acceptable carrier. (Please read the notes on the back before filling this page) ί. 經濟部智慧財產局員工消費合作社印製Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐）This paper size applies to China National Standard (CNS) Α4 specification (210X297 mm)
TW087105843A 1997-04-18 1998-04-17 Novel piperazine derivatives having combined 5HT1A, 5HT1B and 5HT1D recept or antagonist activity and their use for the treatment and prophylaxis of various CNS disorders TW509687B (en)

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