JPS6155498B2 - - Google Patents
Info
- Publication number
- JPS6155498B2 JPS6155498B2 JP54040735A JP4073579A JPS6155498B2 JP S6155498 B2 JPS6155498 B2 JP S6155498B2 JP 54040735 A JP54040735 A JP 54040735A JP 4073579 A JP4073579 A JP 4073579A JP S6155498 B2 JPS6155498 B2 JP S6155498B2
- Authority
- JP
- Japan
- Prior art keywords
- represented
- formula
- benzene
- derivative according
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical class NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 22
- -1 tetrahydrofurfuryl group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 52
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- 238000000862 absorption spectrum Methods 0.000 description 13
- 238000000921 elemental analysis Methods 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 9
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 9
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 8
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 8
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- QFGBDACEUAGHQU-UHFFFAOYSA-N n'-(cyclopropylmethyl)-n-(2,3-dihydro-1h-inden-2-yl)-n'-methylethane-1,2-diamine Chemical compound C1C2=CC=CC=C2CC1NCCN(C)CC1CC1 QFGBDACEUAGHQU-UHFFFAOYSA-N 0.000 description 4
- XFPJLBSJSDCJMU-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-n'-methyl-n'-(oxolan-2-ylmethyl)ethane-1,2-diamine Chemical compound C1C2=CC=CC=C2CC1NCCN(C)CC1CCCO1 XFPJLBSJSDCJMU-UHFFFAOYSA-N 0.000 description 4
- 229960003424 phenylacetic acid Drugs 0.000 description 4
- 239000003279 phenylacetic acid Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- ZVVWZNFSMIFGEP-UHFFFAOYSA-N 2-(4-ethoxyphenyl)acetic acid Chemical compound CCOC1=CC=C(CC(O)=O)C=C1 ZVVWZNFSMIFGEP-UHFFFAOYSA-N 0.000 description 2
- LEGPZHPSIPPYIO-UHFFFAOYSA-N 3-Methoxyphenylacetic acid Chemical compound COC1=CC=CC(CC(O)=O)=C1 LEGPZHPSIPPYIO-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- QDHFDXDMKYJPSC-UHFFFAOYSA-N N-ethylphenylacetamide Chemical compound CCNC(=O)CC1=CC=CC=C1 QDHFDXDMKYJPSC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- CQNIKSXVOOXRSR-UHFFFAOYSA-N 2,2-dimethoxy-2-phenylacetamide Chemical compound COC(OC)(C(N)=O)C1=CC=CC=C1 CQNIKSXVOOXRSR-UHFFFAOYSA-N 0.000 description 1
- RAPIPBRHRYSAHQ-UHFFFAOYSA-N 2-(2,5-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(OC)C(CC(Cl)=O)=C1 RAPIPBRHRYSAHQ-UHFFFAOYSA-N 0.000 description 1
- ABROWERIMKBDEW-UHFFFAOYSA-N 2-(2-ethoxyphenyl)acetic acid Chemical compound CCOC1=CC=CC=C1CC(O)=O ABROWERIMKBDEW-UHFFFAOYSA-N 0.000 description 1
- IVEWTCACRDEAOB-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC=C1CC(O)=O IVEWTCACRDEAOB-UHFFFAOYSA-N 0.000 description 1
- UPEWDRCXLROYOF-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=CC=C1CC(Cl)=O UPEWDRCXLROYOF-UHFFFAOYSA-N 0.000 description 1
- QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 1
- JTSHPHZFTSLRTL-UHFFFAOYSA-N 2-(3,5-diethoxyphenyl)acetic acid Chemical compound CCOC1=CC(CC(O)=O)=CC(OCC)=C1 JTSHPHZFTSLRTL-UHFFFAOYSA-N 0.000 description 1
- FFPAFDDLAGTGPQ-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)acetic acid Chemical compound COC1=CC(CC(O)=O)=CC(OC)=C1 FFPAFDDLAGTGPQ-UHFFFAOYSA-N 0.000 description 1
- HRFLULLBPLPBSW-UHFFFAOYSA-N 2-(3-ethoxyphenyl)acetic acid Chemical compound CCOC1=CC=CC(CC(O)=O)=C1 HRFLULLBPLPBSW-UHFFFAOYSA-N 0.000 description 1
- ULLCOWORODEDBK-UHFFFAOYSA-N 2-(4-propoxyphenyl)acetic acid Chemical compound CCCOC1=CC=C(CC(O)=O)C=C1 ULLCOWORODEDBK-UHFFFAOYSA-N 0.000 description 1
- YJEFUGPGWXNGTO-UHFFFAOYSA-N 2-(4-propoxyphenyl)acetyl chloride Chemical compound CCCOC1=CC=C(CC(Cl)=O)C=C1 YJEFUGPGWXNGTO-UHFFFAOYSA-N 0.000 description 1
- VXWYQEYFYNAZOD-UHFFFAOYSA-N 2-[3-[(4,4-difluoropiperidin-1-yl)methyl]-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound FC1(F)CCN(CC2=NN(CC(=O)N3CCC4=C(C3)N=NN4)C=C2C2=CN=C(NC3CC4=C(C3)C=CC=C4)N=C2)CC1 VXWYQEYFYNAZOD-UHFFFAOYSA-N 0.000 description 1
- KZHUULABPNPTEO-UHFFFAOYSA-N 2-methoxy-2-phenylacetamide Chemical compound COC(C(N)=O)C1=CC=CC=C1 KZHUULABPNPTEO-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- GJANTPSJGSXSDO-UHFFFAOYSA-N n',n'-diethyl-n-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)ethane-1,2-diamine Chemical compound C1=CC=C2C(CNCCN(CC)CC)CCCC2=C1 GJANTPSJGSXSDO-UHFFFAOYSA-N 0.000 description 1
- XMHWCFGQDSVSOI-UHFFFAOYSA-N n'-(cyclopropylmethyl)-n-(2,3-dihydro-1h-inden-1-ylmethyl)-n'-methylethane-1,2-diamine Chemical compound C1CC2=CC=CC=C2C1CNCCN(C)CC1CC1 XMHWCFGQDSVSOI-UHFFFAOYSA-N 0.000 description 1
- WITWIBORFDYHHP-UHFFFAOYSA-N n'-methyl-n'-(oxolan-2-ylmethyl)ethane-1,2-diamine Chemical compound NCCN(C)CC1CCCO1 WITWIBORFDYHHP-UHFFFAOYSA-N 0.000 description 1
- AIDBTLZTSFVXDH-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-ylmethyl)-n'-methyl-n'-(oxolan-2-ylmethyl)ethane-1,2-diamine Chemical compound C1CC2=CC=CC=C2C1CNCCN(C)CC1CCCO1 AIDBTLZTSFVXDH-UHFFFAOYSA-N 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- IFXDDAVRUDKPBW-UHFFFAOYSA-N phenyl acetate;hydrochloride Chemical compound Cl.CC(=O)OC1=CC=CC=C1 IFXDDAVRUDKPBW-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は医薬品として有用な生理作用を持つ新
規なフエニルアセトアミド誘導体およびそれらの
薬理学的に許容できる酸付加塩に関するものであ
る。
さらに詳しくいえば、本発明は強い鎮痛作用を
有し、医薬品として有用な一般式
（式中のＸは炭素数１〜３のアルコキシ基であり
R1は炭素数１〜３のアルキル基であり、R2は炭
素数１〜３のアルキル基、炭素数３〜６の直鎖状
または分枝状のアルケニル基、炭素数４〜７のシ
クロアルキルアルキル基またはテトラハイドロフ
ルフリール基であり、ｎは０〜２の整数であり、
ｍは０または１であり、ｌは３〜５の整数であ
る）で表わされるフエニルアセトアミド誘導体お
よび薬理学的に許容できる塩に関するものであ
る。
本発明の前記一般式（）に表わされるフエニ
ルアセトアミド誘導体は文献未記載の新規化合物
であり、強い鎮痛作用を有し医薬品として有用で
ある。このことはマウスにおいて、酢酸を投与し
たとき生ずるライジング（writhing）反応を顕著
に抑制することにより確認できた。
本発明の前記一般式（）で表わされるフエニ
ルアセトアミド誘導体は、一般式
（式中のR1、R2、ｍおよびｌは前記と同じ意味を
もつ）で表わされる化合物と、一般式
（式中のＸおよびｎは前記と同じ意味をもつ）で
表わされるフエニル酢酸またはその誘導体とを反
応させることにより製造することができる。この
方法において、原料として用いる前記一般式
（）で表わされる化合物は新規化合物であり、
一般式
（式中のｍおよびｌは前記と同じ意味をもつ）で
表わされる化合物とクロル酢酸クロリドとを水−
ジオキサン中で炭酸水素ナトリウムの存在下に反
応させ次いで生成物をアルコーム中で必要あらば
塩基例えば、トリエチルアミンなどの存在下に、
一般式
R1NH2 （）
（式中のR1は前記と同じ意味をもつ）で表わされ
るアミンと反応させ、さらに生成物を一般式、
R2Z （）
（式中のＺはハロゲン原子であり、R2は前記と同
じ意味をもつ）で表わされる化合物と水−アルコ
ール中で炭酸カルウムの存在下に反応させ次いで
生成物をテトラハイドロフラン中で水素化リチウ
ムアルミニウムで還元することにより製造するこ
とができる。この方法において、前記一般式
（）および（）で表わされる化合物をそれぞ
れ反応させる代りに、一般式
（式中のR1およびR2は前記と同じ意味をもつ）で
表わされるアミンを不活性有機溶媒、例えばベン
ゼン中で必要あらばトリエチルアミンなどの塩基
の存在下に反応させてもよい。
本発明において、これら前記一般式（）で表
わされる化合物としては、Ｎ−（１・２・３・４
−テトラハイドロ−１−ナフチルメチル）−N′・
N′−ジメチルエチレンジアミン、Ｎ−（１・２・
３・４−テトラハイドロ−１−ナフチルメチル）
−N′・N′−ジエチルエチレンジアミン、Ｎ−
（１・２・３・４−テトラハイドロ−１−ナフチ
ルメチル）−N′−メチル−N′−アリールエチレン
ジアミン、Ｎ−（１・２・３・４−テトラハイド
ロ−１−ナフチルメチル）−N′−メチル−N′−
３・３−ジメチルアリールエチレンジアミン、Ｎ
−（１・２・３・４−テトラハイドロ−１−ナフ
チルメチル）−N′−メチル−N′−テトラハイドロ
フルフリールエチレンジアミン、Ｎ−（１・２・
３・４−テトラハイドロ−２−ナフチル）−N′・
N′−ジメチルエチレンジアミン、Ｎ−（１・２・
３・４−テトラハイドロ−２−ナフチル）−N′−
エチル−N′−アリールエチレンジアミン、Ｎ−
（１・２・３・４−テトラハイドロ−２−ナフチ
ル）−N′−メチル−N′−３・３−ジメチルアリー
ルエチレンジアミン、Ｎ−（１・２・３・４−テ
トラハイドロ−２−ナフチル）−N′−メチル−
N′−テトラハイドロフルフリールエチレンジア
ミン、Ｎ−（１・２・３・４−テトラハイドロ−
１−ナフチルメチル）−N′−メチル−N′−シクロ
プロピルメチルエチレンジアミン、Ｎ−（１・
２・３・４−テトラハイドロ−２−ナフチル）−
N′−メチル−N′−ジクロプロピルメチルエチレ
ンジアミン、Ｎ−２−インダニル−N′−メチル
−N′−アリールエチレンジアミン、Ｎ−２−イ
ンダニル−N′−メチル−N′−３・３−ジメチル
アリールエチレンジアミン、Ｎ−２−インダニル
−N′−メチル−N′−テトラハイドロフルフリー
ルエチレンジアミン、Ｎ−２−インダニル−
N′−メチル−N′−シクロプロピルメチルエチレ
ンジアミン、Ｎ−１−インダニルメチル−N′・
N′−ジメチルエチレンジアミン、Ｎ−１−イン
ダニルメチル−N′・N′−ジエチルエチレンジア
ミン、Ｎ−１−インダニルメチル−N′−メチル
−N′−アリールエチレンジアミン、Ｎ−１−イ
ンダニルメチル−N′−メチル−N′−３・３−ジ
メチルアリールエチレンジアミン、Ｎ−１−イン
ダニルメチル−N′−メチル−N′−テトラハイド
ロフルフリールエチレンジアミン、Ｎ−１−イン
ダニルメチル−N′−メチル−N′−シクロプロピ
ルメチルエチレンジアミン、Ｎ−（１・２・３・
４−テトラハイドロ−２−ナフチル）−N′・N′−
ジエチルエチレンジアミン、Ｎ−（１・２・３・
４−テトラハイドロ−２−ナフチルメチル）−
N′・N′−ジエチルエチレンジアミン、Ｎ−２−
インダニル−N′・N′−ジエチルエチレンジアミ
ンなどを用いることができる。また前記一般式
（）で表わされるフエニル酢酸およびその誘導
体は公知化合物であり、文献記載の方法に従い容
易に製造することができ、それらの例としてはフ
エニル酢酸、２−、３−または４−メトキシフエ
ニル酢酸、２−、３−または４−エトキシフエニ
ル酢酸、２−、３−または４−プロポキシフエニ
ル酢酸、２・３−、２・４−、２・５−、２・６
−、３・４−または３・５−ジメトキシフエニル
酢酸、２・３−、２・４−、２・５−、２・６
−、３・４−または３・５−ジエトキシフエニル
酢酸、２・３−、２・４−、２・５−、２・６
−、３・４−または３・５−ジプロポキシフエニ
ル酢酸などをあげることができる。
本発明の前記一般式（）で表わされる化合物
と前記一般式（）で表わされるフエニル酢酸ま
たはその誘導体との反応はそれ自体公知のアミド
化反応であり、容易に行うことができる。すなわ
ち、前記一般式（）で表わされる化合物とこれ
と等モルないしやや過剰モルの前記一般式（）
で表わされるフエニル酢酸またはその誘導体とを
不活性有機溶媒中または無溶媒中で前記一般式
（）の化合物と等モルないしやや過剰の縮合
剤、例えばオキシ塩化リンの存在下に数時間加熱
したのち、反応混合物を冷却後ベンゼンなどの有
機溶媒を加え、次いでアルカリ水溶液で洗い、有
機層を乾燥後溶媒を留去し、残留物を減圧蒸留ま
たはカラムクロマトグラフイで精製することによ
り製造することができる。この場合、不活性有機
溶媒としてはベンゼン、テトラハイドロフラン、
ジオキサン、クロロホルム、塩化メチレンなどを
用いることができる。
本発明の目的物は前記一般式（）で表わされ
る化合物と前記一般式（）で表わされるフエニ
ル酢酸またはその誘導体の反応性官能的誘導体を
不活性溶媒、例えばベンゼン、テトラハイドロフ
ラン、ジオキサン、クロロホルム、塩化メチレ
ン、水およびこれらの混合溶媒中で塩基、例えば
ピリジン、トリエチルアミン、炭酸ナトリウム、
炭酸カリウムなどの存在下に反応させても製造す
ることができる。この場合触媒として、適量の４
−（Ｎ・Ｎ−ジメチルアミノ）ピリジン、４−ピ
ロリジノピリジンを用いると反応を好ましく行う
ことができる。このような反応性官能的誘導体と
しては、酸塩化物、酸無水物、混合酸無水物、エ
ステルなどをあげることができる。
本発明の前記一般式（）で表わされるフエニ
ルアセトアミド誘導体において、遊離形の化合物
は油状物質であり、通常の有機溶媒、例えばメタ
ノール、エタノール、クロロホルム、塩化メチレ
ン、エーテル、酢酸エチル、ベンゼンなどに可溶
である。これらの遊離形の化合物は常法に従い酸
付加塩とすることができる。例えば、一般式
（）で表わされるフエニルアセトアミド誘導体
の遊離形の化合物をエーテルに溶かし、次いでこ
の溶液に適量の塩酸ガスを加えることにより塩酸
塩とすることができる。酸付加塩としては塩酸
塩、硫酸塩、スルホン酸塩、安息香酸塩、クエン
酸塩、酒石酸塩、コハク酸塩などをあげることが
でき、これらの酸付加塩は無色の結晶性物質もし
くはガラス状物質であり、相当する遊離形の化合
物と同様に強い鎮痛作用を有する。
本発明の前記一般式（）で表わされるフエニ
ルアセトアミド誘導体は文献未記載の新規化合物
であり、強い鎮痛作用を有し医薬品として有用で
ある。
本発明をさらに詳述するために以下に参考例お
よび実施例を示す。なお参考例および実施例中の
化合物の沸点は未補正である。
参考例 １
１・２・３・４−テトラハイドロ−１−ナフチ
ルメチルアミン塩酸塩20ｇ、炭酸水素ナトリウム
40ｇを水200ml、ジオキサン200mlに溶解し、氷冷
撹拌下にクロル酢酸クロリド30ｇを滴下し２時間
反応する。反応液を濃縮し残留物に水を加え結晶
をろ取しクロロホルム−ｎ−ヘキサンより再結晶
してＮ−（１・２・３・４−テトラハイドロ−１
−ナフチルメチル）クロルアセトアミド16ｇを得
る。このものをメチルアミンのメタノール溶液
140ml（40％溶液）に加え、封管中100℃で３時間
加熱する。冷却後溶媒を留去し10％水酸化ナトリ
ウム水溶液を加えベンゼンで抽出する。ベンゼン
層を水洗し乾燥後減圧下にベンゼンを留去し、Ｎ
−（１・２・３・４−テトラハイドロ−１−ナフ
チルメチル）−α−メチルアミノアセトアミド14
ｇを得る。これと３・３−ジメチルアリールクロ
リド8.4ｇ、炭酸カリウム20ｇ、ヨウ化ナトリウ
ム１ｇをエタノール200ml、水200mlにけんだくし
４時間加熱還流する。冷却後溶媒を留去し、10％
水酸化ナトリウム水溶液を加えベンゼンで抽出す
る。ベンゼン層を水洗し乾燥後減圧下に濃縮し
て、Ｎ−（１・２・３・４−テトラハイドロ−１
−ナフチルメチル）−α−（Ｎ−メチル−Ｎ−３・
３−ジメチルアリールアミノ）アセトアミド18ｇ
を得る。このものをテトラハイドロフラン60mlに
溶解し、水素化リチウムアルミニウム10ｇのテト
ラハイドロフラン300mlのけんだく液に氷冷撹拌
下に滴下し、さらに室温で１時間反応させ、一夜
加熱還流する。冷却後10％水酸化ナトリウム水溶
液を加え不溶物をろ去しろ液に水を加え減圧下に
濃縮し、残留物をエーテルで抽出し水洗し乾燥す
る。エーテルを留去し残留物を減圧蒸留（160〜
165℃／１mmHg）し無色油状物のＮ−（１・２・
３・４−テトラハイドロ−１−ナフチルメチル）
−N′−メチル−N′−３・３−ジメチルアリール
エチレンジアミン15ｇを得る。
赤外線吸収スペクトル（液膜）
νNH：3300cm-1
元素分析値 C19H30N2として
Ｃ％ Ｈ％ Ｎ％
理論値 79.66 10.56 9.78
実測値 79.53 10.51 9.89
核磁気共鳴スペクトル（CDCl3）
δ：1.54（ｓ、1H）、1.62（ｓ、3H）、1.72
（ｓ、3H）、2.18（ｓ、3H）、1.5〜3.1（ｍ、
15H）、5.0〜5.3（ｍ、1H）、6.9〜7.3（ｍ、
4H）
以下同様な方法により下記の化合物を製造する
ことができる。
The present invention relates to novel phenylacetamide derivatives having physiological effects useful as pharmaceuticals and their pharmacologically acceptable acid addition salts. More specifically, the present invention discloses a general formula that has a strong analgesic effect and is useful as a pharmaceutical. (X in the formula is an alkoxy group having 1 to 3 carbon atoms,
R 1 is an alkyl group having 1 to 3 carbon atoms, and R 2 is an alkyl group having 1 to 3 carbon atoms, a linear or branched alkenyl group having 3 to 6 carbon atoms, or a cycloalkyl group having 4 to 7 carbon atoms. an alkylalkyl group or a tetrahydrofurfuryl group, n is an integer of 0 to 2,
m is 0 or 1, l is an integer of 3 to 5) and a pharmacologically acceptable salt thereof. The phenylacetamide derivative represented by the general formula () of the present invention is a new compound that has not been described in any literature, and has a strong analgesic effect and is useful as a pharmaceutical. This was confirmed in mice by significantly suppressing the writhing response that occurs when acetic acid is administered. The phenylacetamide derivative of the present invention represented by the general formula () is represented by the general formula (In the formula, R 1 , R 2 , m and l have the same meanings as above) and a compound represented by the general formula It can be produced by reacting with phenylacetic acid or a derivative thereof represented by the formula (wherein X and n have the same meanings as above). In this method, the compound represented by the general formula () used as a raw material is a new compound,
general formula A compound represented by (m and l in the formula have the same meanings as above) and chloroacetic acid chloride are combined in water-
The product is reacted in dioxane in the presence of sodium bicarbonate and the product is reacted in an alcohol if necessary in the presence of a base such as triethylamine.
It is reacted with an amine represented by the general formula R 1 NH 2 () (R 1 in the formula has the same meaning as above), and the product is further reacted with the amine represented by the general formula R 2 Z () (Z in the formula is a halogen atom). and R 2 has the same meaning as above) in water-alcohol in the presence of potassium carbonate, and then reducing the product with lithium aluminum hydride in tetrahydrofuran. can do. In this method, instead of reacting the compounds represented by the general formulas () and (), respectively, the compounds represented by the general formula The amine represented by the formula (wherein R 1 and R 2 have the same meanings as above) may be reacted in an inert organic solvent, for example benzene, if necessary in the presence of a base such as triethylamine. In the present invention, the compounds represented by the above general formula () include N-(1, 2, 3, 4
-tetrahydro-1-naphthylmethyl)-N'
N'-dimethylethylenediamine, N-(1.2.
3,4-tetrahydro-1-naphthylmethyl)
-N'・N'-diethylethylenediamine, N-
(1,2,3,4-tetrahydro-1-naphthylmethyl)-N'-methyl-N'-arylethylenediamine, N-(1,2,3,4-tetrahydro-1-naphthylmethyl)-N ′-methyl-N′-
3,3-dimethylarylethylenediamine, N
-(1,2,3,4-tetrahydro-1-naphthylmethyl)-N'-methyl-N'-tetrahydrofurfurylethylenediamine, N-(1,2,
3,4-tetrahydro-2-naphthyl)-N'.
N'-dimethylethylenediamine, N-(1.2.
3,4-tetrahydro-2-naphthyl)-N'-
Ethyl-N'-arylethylenediamine, N-
(1,2,3,4-tetrahydro-2-naphthyl)-N'-methyl-N'-3,3-dimethylarylethylenediamine, N-(1,2,3,4-tetrahydro-2-naphthyl) )-N'-methyl-
N'-tetrahydrofurfurylethylenediamine, N-(1,2,3,4-tetrahydro-
1-naphthylmethyl)-N'-methyl-N'-cyclopropylmethylethylenediamine, N-(1.
2,3,4-tetrahydro-2-naphthyl)-
N'-Methyl-N'-dichloropropylmethylethylenediamine, N-2-indanyl-N'-methyl-N'-arylethylenediamine, N-2-indanyl-N'-methyl-N'-3,3-dimethylaryl Ethylenediamine, N-2-indanyl-N'-methyl-N'-tetrahydrofurfurylethylenediamine, N-2-indanyl-
N'-methyl-N'-cyclopropylmethylethylenediamine, N-1-indanylmethyl-N'.
N'-dimethylethylenediamine, N-1-indanylmethyl-N'/N'-diethylethylenediamine, N-1-indanylmethyl-N'-methyl-N'-arylethylenediamine, N-1-indanylmethyl- N'-Methyl-N'-3,3-dimethylarylethylenediamine, N-1-indanylmethyl-N'-methyl-N'-tetrahydrofurfurylethylenediamine, N-1-indanylmethyl-N'- Methyl-N'-cyclopropylmethylethylenediamine, N-(1, 2, 3,
4-tetrahydro-2-naphthyl)-N'・N'-
Diethylethylenediamine, N-(1, 2, 3,
4-tetrahydro-2-naphthylmethyl)-
N'・N'-diethylethylenediamine, N-2-
Indanyl-N'.N'-diethylethylenediamine and the like can be used. In addition, phenylacetic acid and its derivatives represented by the general formula () are known compounds and can be easily produced according to methods described in the literature; examples thereof include phenylacetic acid, 2-, 3- or 4-methoxy Phenylacetic acid, 2-, 3- or 4-ethoxyphenylacetic acid, 2-, 3- or 4-propoxyphenylacetic acid, 2, 3-, 2, 4-, 2, 5-, 2, 6
-, 3,4- or 3,5-dimethoxyphenylacetic acid, 2,3-, 2,4-, 2,5-, 2,6
-, 3, 4- or 3, 5-diethoxyphenylacetic acid, 2, 3-, 2, 4-, 2, 5-, 2, 6
-, 3,4- or 3,5-dipropoxyphenylacetic acid. The reaction between the compound represented by the above general formula () of the present invention and the phenylacetic acid represented by the above general formula () or a derivative thereof is an amidation reaction that is known per se and can be easily carried out. That is, the compound represented by the above general formula () and the same molar to slightly excess molar amount of the above general formula ()
Phenyl acetic acid or a derivative thereof represented by is heated in an inert organic solvent or in the absence of a solvent in the presence of an equimolar to slightly excess amount of a condensing agent, such as phosphorus oxychloride, as the compound of the general formula () for several hours. It can be produced by cooling the reaction mixture, adding an organic solvent such as benzene, then washing with an aqueous alkaline solution, drying the organic layer, distilling off the solvent, and purifying the residue by vacuum distillation or column chromatography. can. In this case, the inert organic solvent is benzene, tetrahydrofuran,
Dioxane, chloroform, methylene chloride, etc. can be used. The object of the present invention is a compound represented by the general formula () and a reactive functional derivative of phenyl acetic acid or its derivative represented by the general formula () in an inert solvent such as benzene, tetrahydrofuran, dioxane, chloroform. , methylene chloride, water and a base such as pyridine, triethylamine, sodium carbonate, in water and a mixed solvent thereof.
It can also be produced by reacting in the presence of potassium carbonate or the like. In this case, as a catalyst, an appropriate amount of 4
The reaction can be preferably carried out using -(N·N-dimethylamino)pyridine or 4-pyrrolidinopyridine. Such reactive functional derivatives include acid chlorides, acid anhydrides, mixed acid anhydrides, esters, and the like. In the phenylacetamide derivative represented by the above general formula () of the present invention, the free form of the compound is an oily substance, and it can be dissolved in common organic solvents such as methanol, ethanol, chloroform, methylene chloride, ether, ethyl acetate, benzene, etc. It is soluble. These free-form compounds can be converted into acid addition salts according to conventional methods. For example, the free form of the phenylacetamide derivative represented by the general formula () can be dissolved in ether, and then an appropriate amount of hydrochloric acid gas is added to this solution to form a hydrochloride. Examples of acid addition salts include hydrochloride, sulfate, sulfonate, benzoate, citrate, tartrate, succinate, etc. These acid addition salts are colorless crystalline substances or glassy substances. substance, which, like the corresponding free form of the compound, has a strong analgesic effect. The phenylacetamide derivative of the present invention represented by the general formula () is a new compound that has not been described in any literature, and has a strong analgesic effect and is useful as a pharmaceutical. Reference examples and examples are shown below to further explain the present invention in detail. Note that the boiling points of the compounds in Reference Examples and Examples are uncorrected. Reference example 1 1,2,3,4-tetrahydro-1-naphthylmethylamine hydrochloride 20g, sodium hydrogen carbonate
40g was dissolved in 200ml of water and 200ml of dioxane, and 30g of chloroacetic acid chloride was added dropwise with stirring under ice cooling, and the mixture was reacted for 2 hours. The reaction solution was concentrated, water was added to the residue, the crystals were collected by filtration, and recrystallized from chloroform-n-hexane to give N-(1,2,3,4-tetrahydro-1
16 g of -naphthylmethyl)chloroacetamide are obtained. This is a methanol solution of methylamine.
Add to 140 ml (40% solution) and heat at 100°C for 3 hours in a sealed tube. After cooling, the solvent is distilled off, a 10% aqueous sodium hydroxide solution is added, and the mixture is extracted with benzene. After washing the benzene layer with water and drying, benzene was distilled off under reduced pressure, and N
-(1,2,3,4-tetrahydro-1-naphthylmethyl)-α-methylaminoacetamide 14
get g. This, 8.4 g of 3,3-dimethylaryl chloride, 20 g of potassium carbonate, and 1 g of sodium iodide were dissolved in 200 ml of ethanol and 200 ml of water, and heated under reflux for 4 hours. After cooling, remove the solvent and reduce to 10%
Add aqueous sodium hydroxide solution and extract with benzene. The benzene layer was washed with water, dried, and concentrated under reduced pressure to obtain N-(1,2,3,4-tetrahydro-1
-naphthylmethyl)-α-(N-methyl-N-3.
3-dimethylarylamino)acetamide 18g
get. This product was dissolved in 60 ml of tetrahydrofuran, and added dropwise to a suspension of 10 g of lithium aluminum hydride in 300 ml of tetrahydrofuran while stirring on ice, reacted for 1 hour at room temperature, and heated under reflux overnight. After cooling, add 10% aqueous sodium hydroxide solution, remove insoluble matter by filtration, add water to the filtrate, concentrate under reduced pressure, and extract the residue with ether, wash with water, and dry. The ether is distilled off and the residue is distilled under reduced pressure (160~
165℃/1mmHg) and colorless oil N-(1.2.
3,4-tetrahydro-1-naphthylmethyl)
15 g of -N'-methyl-N'-3,3-dimethylarylethylenediamine is obtained. Infrared absorption spectrum (liquid film) νNH: 3300cm -1 Elemental analysis value C 19 H 30 As N 2 C% H% N% Theoretical value 79.66 10.56 9.78 Actual value 79.53 10.51 9.89 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.54 ( s, 1H), 1.62 (s, 3H), 1.72
(s, 3H), 2.18 (s, 3H), 1.5~3.1 (m,
15H), 5.0-5.3 (m, 1H), 6.9-7.3 (m,
4H) The following compounds can be produced by the same method.
【表】
実施例 １
４−メトキシフエニル酢酸５ｇをベンゼン30ml
に溶解しオキシ塩化リン６ｇを滴下する。室温で
30分間撹拌したのち氷冷下にＮ−（１・２・３・
４−テトラハイドロ−１−ナフチルメチル）−
N′−メチル−N′−テトラハイドロフルフリール
エチレンジアミン６ｇのベンゼン20mlの溶液を滴
下し室温で１時間撹拌したのち、３時間加熱還流
する。冷却後10％水酸化ナトリウム水溶液を加え
ベンゼンで抽出し水洗し乾燥後溶媒を留去する。
残留物をアルミナカラムクロマトグラフイ（ベン
ゼン−酢酸エチル）で精製し、Ｎ−（１・２・
３・４−テトラハイドロ−１−ナフチルメチル）
−Ｎ−２−（Ｎ−メチル−Ｎ−テトラハイドロフ
ルフリールアミノ）エチル−４−メトキシフエニ
ルアセトアミドを6.5ｇ得る。（黄色油状物）
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C28H38N2O3として
Ｃ％ Ｈ％ Ｎ％
理論値 74.63 8.50 6.22
実測値 74.50 8.45 5.95
核磁気共鳴スペクトル（CDCl3）
δ：1.0〜4.1（ｍ、27H）、3.78（ｓ、3H）、6.6
〜7.3（ｍ、8H）
実施例 ２
４−メトキシフエニル酢酸５ｇをベンゼン30ml
に溶解し、この溶液にオキシ塩化リン６ｇを滴下
し室温で30分間反応させる。反応液を氷冷下撹拌
しＮ−（１・２・３・４−テトラハイドロ−１−
ナフチルメチル）−N′−メチル−N′−３・３−ジ
メチルアリールエチレンジアミン5.7ｇのベンゼ
ン20ml溶液を滴下する。室温で１時間反応させた
のち、６時間加熱還流する。反応液を冷却後10％
水酸化ナトリウム水溶液を加えベンゼン層を分取
し水洗し乾燥する。減圧下に溶媒を留去し、残留
物をアルミナカラムクロマトグラフイ（ベンゼン
−酢酸エチル）で精製し、淡黄色油状物のＮ−
（１・２・３・４−テトラハイドロ−１−ナフチ
ルメチル）−Ｎ−２−（Ｎ−メチル−Ｎ−３・３−
ジメチルアリールアミノ）エチル−４−メトキシ
フエニルアセトアミド5.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C28H38N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 77.38 8.81 6.45
実測値 77.64 8.79 6.16
核磁気共鳴スペクトル（CDCl3）
δ：1.61（ｓ、3H）、1.70（ｓ、3H）、3.80
（ｓ、3H）、1.6〜3.9（ｍ、20H）、5.0〜5.3
（ｍ、1H）、6.7〜7.3（ｍ、8H）
実施例 ３
４−メトキシフエニル酢酸6.6ｇをベンゼン50
mlに溶解し、この溶液にオキシ塩化リン6.2ｇを
滴下し次いで室温30分間反応させる。反応液を氷
冷し撹拌下にＮ−（１・２・３・４−テトラハイ
ドロ−１−ナフチルメチル）−N′・N′−ジエチル
エチレンジアミン6.2ｇのベンゼン50ml溶液を滴
下する。室温で１時間反応させたのち、４時間加
熱還流する。反応液を冷却し10％水酸化ナトリウ
ム水溶液を加えベンゼン層を分取し水洗し乾燥す
る。減圧下に溶媒を留去し残留物を減圧蒸留
（220〜225℃／0.2mmHg）し淡黄色油状物のＮ−
（１・２・３・４−テトラハイドロ−１−ナフチ
ルメチル）−Ｎ−２−（Ｎ・Ｎ−ジエチルアミノ）
−エチル−４−メトキシフエニルアセトアミド
5.5ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1635cm-1
元素分析値 C26H36N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 76.43 8.88 6.86
実測値 76.69 8.67 6.93
核磁気共鳴スペクトル（CDCl3）
δ：0.95（ｔ、ｔ、3H、3H）、2.46（ｑ、ｑ、
2H、2H）、1.5〜3.9（ｍ、15H）、3.75（ｓ、
3H）、6.6〜7.4（ｍ、8H）
実施例 ４
４−メトキシフエニル酢酸6.6ｇをベンゼン30
mlに溶解しオキシ塩化リン6.1ｇを滴下し室温で
30分間反応させる。この溶液に氷冷撹拌下、Ｎ−
２−インダニル−N′・N′−ジエチルエチレンジ
アミン6.1ｇのベンゼン20ml溶液を滴下し室温で
１時間撹拌したのち５時間加熱還流する。反応液
を冷却後10％水酸化ナトリウム水溶液を加えベン
ゼン層を分取し水洗し乾燥する。減圧下に溶媒を
留去し、残留物を減圧蒸留（220〜225℃／0.8mm
Hg）淡黄色油状物のＮ−２−インダニル−Ｎ−
２−（Ｎ・Ｎ−ジエチルアミノ）エチル−４−メ
トキシフエニルアセトアミド8.2ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C24H32N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 75.75 8.48 7.36
実測値 75.68 8.42 7.36
核磁気共鳴スペクトル（CDCl3）
δ：0.98（ｔ、ｔ、3H、3H）、2.2〜4.0（ｍ、
15H）、3.80（ｓ、3H）、6.8〜7.3（ｍ、8H）
実施例 ５
４−メトキシフエニル酢酸3.32ｇをベンゼン20
mlに溶解しオキシ塩化リン3.1ｇを加え室温で30
分間反応させ次いでこの反応液に氷冷下Ｎ−
（１・２・３・４−テトラハイドロ−２−ナフチ
ル−N′・N′−ジエチルエチレンジアミン3.1ｇの
ベンゼン10ml溶液を撹忰しながら加え室温で１時
間反応させ、さらに６時間加熱還流する。反応液
を冷却したのち10％水酸化ナトリウム水溶液を加
え、ベンゼン層を水洗し乾燥する。減圧下に溶媒
を留去し残留物を減圧蒸留（205〜210℃／0.4mm
Hg）し淡黄色油状物のＮ−（１・２・３・４−テ
トラハイドロ−２−−ナフチル）−Ｎ−２−（Ｎ・
Ｎ−ジエチルアミノ）エチル−４−メトキシフエ
ニルアセトアミド3.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C25H34N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 76.10 8.69 7.10
実測値 76.08 8.75 7.36
核磁気共鳴スペクトル（CDCl3）
δ：1.05（ｔ、ｔ、3H、3H）、1.5〜4.4（ｍ、
17H）、3.80（ｓ、3H）、6.7〜7.3（ｍ、8H）
実施例 ６
Ｎ−２−インダニル−N′−メチル−N′−シク
ロプロピルメチルエチレンジアミン２ｇ、４−
（Ｎ・Ｎ−ジメチルアミノ）ピリジン50mg、トリ
エチルアミン３ｇを塩化メチレン30mlに溶解し、
フエニル酢酸クロリド1.6ｇの塩化メチレン５ml
溶液を氷冷下に滴下し室温で２時間反応させる。
減圧下に溶媒を留去したのち、10％水酸化ナトリ
ウム水溶液を加え、ベンゼンで抽出する。ベンゼ
ン層を水洗し乾燥したのち、減圧下に溶媒を留去
し残留物をアルミナカラムクロマトグラフイ（ベ
ンゼン−酢酸エチル）で精製し淡黄色油状物のＮ
−２−インダニル−Ｎ−２−（Ｎ−メチル−Ｎ−
シクロプロピルメチルアミノ）エチルフエニルア
セトアミド1.8ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C24H30N2Oとして
Ｃ％ Ｈ％ Ｎ％
理論値 79.51 8.34 7.73
実測値 79.39 8.29 7.81
核磁気共鳴スペクトル（CDCl3）
δ：０〜1.0（ｍ、5H）、2.0〜4.0（ｍ、14H）、
3.80（ｓ、2H）、7.0〜7.5（ｍ、9H）
実施例 ７
Ｎ−２−インダニル−N′−メチル−N′−テト
ラハイドロフルフリールエチレンジアミン1.0
ｇ、４−（Ｎ・Ｎ−ジメチルアミノ）ピリジン50
mg、トリエチルアミン１ｇを塩化メチレン10mlに
溶解し、氷冷撹拌下に２・５−ジメトキシフエニ
ル酢酸クロリド1.2ｇの塩化メチレン10ml溶液を
滴下したのち室温で３時間撹拌する。減圧下に反
応液を濃縮し残留物に10％水酸化ナトリウム水溶
液を加えベンゼンで抽出する。ベンゼン層を水洗
し乾燥したのち減圧下に溶媒を留去し残留物をア
ルミナカラムクロマトグラフイ（ベンゼン−酢酸
エチル）で精製し、淡黄色油状物Ｎ−２−インダ
ニル−Ｎ−２−（Ｎ−メチル−Ｎ−テトラハイド
ロフルフリールアミノ）エチル−２・５−ジメト
キシフエニルアセトアミド1.2ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C27H36N2O4として
Ｃ％ Ｈ％ Ｎ％
理論値 71.65 8.02 6.19
実測値 71.49 8.98 6.29
核磁気共鳴スペクトル（CDCl3）
δ：1.5〜4.0（ｍ、23H）、3.76（ｓ、ｓ、3H、
3H）、6.7〜7.4（ｍ、7H）
実施例 ８
Ｎ−２−インダニル−N′−メチル−N′−シク
ロプロピルメチルエチレンジアミン5.0ｇ、トリ
エチルアミン５ml、４−（Ｎ・Ｎ−ジメチルアミ
ノ）ピリジン50mgを塩化メチレン50mlに溶解し、
この溶液に３・４−ジメトキシフエニル酢酸クロ
リド7.3ｇの塩化メチレン30ml溶液を滴下し氷冷
下１時間さらに室温で３時間反応する。反応液を
減圧下に濃縮し残留物に10％水酸化ナトリウム水
溶液を加えエーテル抽出する。エーテル層を水洗
し乾燥したのち、減圧下に濃縮する。残留物をア
ルミナカラムクロマトグラフイ（ベンゼン−酢酸
エチル）で精製し淡黄色油状物のＮ−２−インダ
ニル−Ｎ−２−（Ｎ−メチル−Ｎ−シクロプロピ
ルメチルアミノ）エチル−３・４−ジメトキシフ
エニルアセトアミド4.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C26H34N2O3として
Ｃ％ Ｈ％ Ｎ％
理論値 73.90 8.11 6.63
実測値 73.99 8.10 6.81
核磁気共鳴スペクトル（CDCl3）
δ：０〜1.0（ｍ、5H）、2.0〜4.0（ｍ、16H）、
3.83（ｓ、ｓ、3H、3H）、6.55〜7.35（ｍ、
7H）
実施例 ９
Ｎ−２−インダニル−N′−メチル−N′−シク
ロプロピルメチルエチレンジアミン５ｇ、トリエ
チルアミン５ml、４−（Ｎ・Ｎ−ジメチルアミ
ノ）ピリジン30mgを塩化メチレン30mlに溶解し、
この溶液に氷冷撹拌下２−メトキシフエニル酢酸
クロリド7.7ｇの塩化メチレン20ml溶液を滴下し
氷冷下30分さらに室温で２時間反応させる。反応
液を減圧下に濃縮し残留物に10％水酸化ナトリウ
ム水溶液を加えエーテルで抽出する。エーテル層
を水洗し乾燥したのち、減圧下に濃縮する。残留
物をアルミナカラムクロマトグラフイ（ベンゼン
−酢酸エチル）で精製しＮ−２−インダニル−Ｎ
−２−（Ｎ−メチル−Ｎ−シクロプロピルメチル
アミノ）エチル−２−メトキシフエニルアセトア
ミド3.7ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C25H32N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 76.49 8.22 7.14
実測値 76.60 8.33 7.31
核磁気共鳴スペクトル（CDCl3）
δ：０〜1.0（ｍ、5H）、2.0〜3.95（ｍ、
16H）、3.73（ｓ、3H）、6.65〜7.45（ｍ、
8H）
実施例 10
Ｎ−２−インダニル−N′−メチル−N′−テト
ラハイドロフルフリールエチレンジアミン5.5
ｇ、トリエチルアミン５ml、４−（Ｎ・Ｎ−ジメ
チルアミノ）ピリジン30mgを塩化メチレン30mlに
溶解し、この溶液に氷冷撹拌下、フエニル酢酸ク
ロリド６ｇの塩化メチレン10ml溶液を滴下する。
氷冷下に30分間反応させたのち、室温で２時間反
応させる。反応液を減圧下に濃縮し残留物に10％
水酸化ナトリウム水溶液を加えエーテル抽出し、
エーテル層を水洗し乾燥したのち、減圧下に濃縮
する。残留物をアルミナカラムクロマトグラフイ
（ベンゼン−酢酸エチル）で精製し淡黄色油状物
のＮ−２−インダニル−Ｎ−２−（Ｎ−メチル−
テトラハイドロフルフリールアミノ）エチルフエ
ニルアセトアミド4.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1640cm-1
元素分析値 C25H32N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 76.49 8.22 7.14
実測値 76.50 8.28 7.24
核磁気共鳴スペクトル（CDCl3）
δ：1.0〜4.2（ｍ、23H）、6.7〜7.7（ｍ、9H）
実施例 11
Ｎ−２−インダニル−N′−メチル−N′−テト
ラハイドロフルフリールエチレンジアミン5.5
ｇ、トリエチルアミン５ml、４−（Ｎ・Ｎ−ジメ
チルアミノ）ピリジン50mgを塩化メチレン50mlに
溶解し、この溶液に氷冷撹拌下、４−ｎ−プロポ
キシフエニル酢酸クロリド8.5ｇの塩化メチレン
20ml溶液を滴下する。氷冷下に30分間さらに室温
で３時間反応する。反応液を減圧下に濃縮し残留
物に10％水酸化ナトリウム水溶液を加えエーテル
抽出する。エーテル層を水洗し乾燥したのち、減
圧下に濃縮し残留物をアルミナカラムクロマトグ
ラフイ（ベンゼン−酢酸エチル）で精製し淡黄色
油状物のＮ−２−インダニル−Ｎ−２−（Ｎ−メ
チル−Ｎ−テトラハイドロフルフリールアミノ）
エチル−４−ｎ−プロポキシフエニルアセトアミ
ド5.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1635cm-1
元素分析値 C28H38N2O3として
Ｃ％ Ｈ％ Ｎ％
理論値 74.63 8.50 6.22
実測値 74.71 8.43 6.21
核磁気共鳴スペクトル（CDCl3）
δ：0.9〜4.15（ｍ、27H）、1.05（ｔ、3H）、
6.6〜7.4（ｍ、8H）
実施例 12
Ｎ−１−インダニルメチル−N′・N′−ジエチ
ルエチレンジアミン６ｇ、４−メトキシフエニル
酢酸５ｇ、オキシ塩化リン4.6ｇをベンゼン50ml
に溶かし２時間加熱還流する。反応液を冷却し10
％水酸化ナトリウム水溶液を加えベンゼン層を分
取し水洗し乾燥する。減圧下に溶媒を留去し残留
物を減圧蒸留（250〜254℃／0.5mmHg）し淡黄色
油状物のＮ−１−インダニルメチル−Ｎ−２−
（Ｎ・Ｎ−ジエチルアミノ）エチル−４−メトキ
シフエニルアセトアミド7.3ｇを得る。
赤外線吸収スペクトル（液膜）
νCO：1635cm-1
元素分析値 C25H34N2O2として
Ｃ％ Ｈ％ Ｎ％
理論値 76.10 8.69 7.10
実測値 76.25 8.60 7.10
核磁気共鳴スペクトル（CDCl3）
δ：1.0（ｔ、ｔ、3H、3H）、1.55〜4.0（ｍ、
17H）、3.77（ｓ、3H）、6.67〜7.35（ｍ、
8H）
実施例 13
Ｎ−（１・２・３・４−テトラハイドロ−１−
ナフチルメチル）−Ｎ−２−（Ｎ−メチル−Ｎ−テ
トラハイドロフルフリールアミノ）エチル−４−
メトキシフエニルアセトアミド0.5ｇをエーテル
20mlに溶解し、この溶液に適量の塩酸ガスを吹き
込む。減圧下に反応液を濃縮すると無色透明のＮ
−（１・２・３・４−テトラハイドロ−１−ナフ
チルメチル）−Ｎ−２−（Ｎ−メチル−Ｎ−テトラ
ハイドロフルフリールアミノ）エチル−４−メト
キシフエニルアセトアミド塩酸塩0.5ｇを得る。[Table] Example 1 5g of 4-methoxyphenylacetic acid and 30ml of benzene
6 g of phosphorus oxychloride was added dropwise. at room temperature
After stirring for 30 minutes, add N-(1, 2, 3,
4-tetrahydro-1-naphthylmethyl)-
A solution of 6 g of N'-methyl-N'-tetrahydrofurfurylethylenediamine in 20 ml of benzene was added dropwise, stirred at room temperature for 1 hour, and then heated under reflux for 3 hours. After cooling, add 10% aqueous sodium hydroxide solution, extract with benzene, wash with water, dry, and evaporate the solvent.
The residue was purified by alumina column chromatography (benzene-ethyl acetate) and N-(1.2.
3,4-tetrahydro-1-naphthylmethyl)
6.5 g of -N-2-(N-methyl-N-tetrahydrofurfurylamino)ethyl-4-methoxyphenylacetamide is obtained. (yellow oil) Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 28 H 38 N 2 O 3 C% H% N% Theoretical value 74.63 8.50 6.22 Actual value 74.50 8.45 5.95 Nuclear magnetic resonance spectrum ( CDCl 3 ) δ: 1.0-4.1 (m, 27H), 3.78 (s, 3H), 6.6
~7.3 (m, 8H) Example 2 5 g of 4-methoxyphenylacetic acid in 30 ml of benzene
6 g of phosphorus oxychloride is added dropwise to this solution and allowed to react at room temperature for 30 minutes. The reaction solution was stirred under ice-cooling to give N-(1,2,3,4-tetrahydro-1-
A solution of 5.7 g of (naphthylmethyl)-N'-methyl-N'-3,3-dimethylarylethylenediamine in 20 ml of benzene was added dropwise. After reacting at room temperature for 1 hour, the mixture was heated under reflux for 6 hours. 10% after cooling the reaction solution
Add an aqueous sodium hydroxide solution, separate the benzene layer, wash with water, and dry. The solvent was distilled off under reduced pressure, and the residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain a pale yellow oily N-
(1,2,3,4-tetrahydro-1-naphthylmethyl)-N-2-(N-methyl-N-3,3-
5.3 g of dimethylarylamino)ethyl-4-methoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 28 H 38 N 2 O 2 C% H% N% Theoretical value 77.38 8.81 6.45 Actual value 77.64 8.79 6.16 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.61 (s, 3H), 1.70 (s, 3H), 3.80
(s, 3H), 1.6-3.9 (m, 20H), 5.0-5.3
(m, 1H), 6.7-7.3 (m, 8H) Example 3 6.6g of 4-methoxyphenyl acetic acid was added to 50% of benzene.
ml, and 6.2 g of phosphorus oxychloride was added dropwise to this solution, followed by reaction at room temperature for 30 minutes. The reaction solution was cooled on ice, and a solution of 6.2 g of N-(1,2,3,4-tetrahydro-1-naphthylmethyl)-N',N'-diethylethylenediamine in 50 ml of benzene was added dropwise while stirring. After reacting at room temperature for 1 hour, the mixture was heated under reflux for 4 hours. Cool the reaction solution, add 10% aqueous sodium hydroxide solution, separate the benzene layer, wash with water, and dry. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure (220-225℃/0.2mmHg) to obtain a pale yellow oily N-
(1,2,3,4-tetrahydro-1-naphthylmethyl)-N-2-(N/N-diethylamino)
-ethyl-4-methoxyphenylacetamide
Obtain 5.5g. Infrared absorption spectrum (liquid film) νCO: 1635 cm -1 Elemental analysis value C 26 H 36 N 2 O 2 C% H% N% Theoretical value 76.43 8.88 6.86 Actual value 76.69 8.67 6.93 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0.95 (t, t, 3H, 3H), 2.46 (q, q,
2H, 2H), 1.5-3.9 (m, 15H), 3.75 (s,
3H), 6.6-7.4 (m, 8H) Example 4 6.6g of 4-methoxyphenylacetic acid was dissolved in benzene 30
ml and dropwise added 6.1 g of phosphorus oxychloride at room temperature.
Incubate for 30 minutes. Add N- to this solution under ice-cooling and stirring.
A solution of 6.1 g of 2-indanyl-N'.N'-diethylethylenediamine in 20 ml of benzene was added dropwise, stirred at room temperature for 1 hour, and then heated under reflux for 5 hours. After cooling the reaction solution, add 10% aqueous sodium hydroxide solution and separate the benzene layer, wash with water and dry. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure (220-225℃/0.8mm
Hg) Pale yellow oil N-2-indanyl-N-
8.2 g of 2-(N.N-diethylamino)ethyl-4-methoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 24 H 32 N 2 O 2 C% H% N% Theoretical value 75.75 8.48 7.36 Actual value 75.68 8.42 7.36 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0.98 (t, t, 3H, 3H), 2.2~4.0 (m,
15H), 3.80 (s, 3H), 6.8-7.3 (m, 8H) Example 5 3.32 g of 4-methoxyphenyl acetic acid was dissolved in benzene 20
ml, add 3.1 g of phosphorus oxychloride, and stir at room temperature for 30 minutes.
After reacting for a minute, the reaction solution was added to N-
(A solution of 3.1 g of 1,2,3,4-tetrahydro-2-naphthyl-N',N'-diethylethylenediamine in 10 ml of benzene was added with stirring, allowed to react at room temperature for 1 hour, and further heated under reflux for 6 hours. After cooling the reaction solution, 10% aqueous sodium hydroxide solution was added, and the benzene layer was washed with water and dried.The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure (205-210℃/0.4mm).
Hg) and pale yellow oil N-(1,2,3,4-tetrahydro-2-naphthyl)-N-2-(N.
3.3 g of N-diethylamino)ethyl-4-methoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 25 H 34 N 2 O 2 C% H% N% Theoretical value 76.10 8.69 7.10 Actual value 76.08 8.75 7.36 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.05 (t, t, 3H, 3H), 1.5-4.4 (m,
17H), 3.80 (s, 3H), 6.7-7.3 (m, 8H) Example 6 N-2-indanyl-N'-methyl-N'-cyclopropylmethylethylenediamine 2g, 4-
Dissolve 50 mg of (N/N-dimethylamino)pyridine and 3 g of triethylamine in 30 ml of methylene chloride,
1.6 g of phenyl acetate chloride 5 ml of methylene chloride
The solution was added dropwise under ice cooling and allowed to react at room temperature for 2 hours.
After distilling off the solvent under reduced pressure, 10% aqueous sodium hydroxide solution is added, and the mixture is extracted with benzene. After washing the benzene layer with water and drying, the solvent was distilled off under reduced pressure, and the residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain a pale yellow oily N.
-2-indanyl-N-2-(N-methyl-N-
1.8 g of cyclopropylmethylamino)ethylphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 24 H 30 N 2 O C% H% N% Theoretical value 79.51 8.34 7.73 Actual value 79.39 8.29 7.81 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0 ~1.0 (m, 5H), 2.0 ~ 4.0 (m, 14H),
3.80 (s, 2H), 7.0-7.5 (m, 9H) Example 7 N-2-indanyl-N'-methyl-N'-tetrahydrofurfurylethylenediamine 1.0
g, 4-(N・N-dimethylamino)pyridine 50
1 g of triethylamine are dissolved in 10 ml of methylene chloride, and a solution of 1.2 g of 2,5-dimethoxyphenylacetic acid chloride in 10 ml of methylene chloride is added dropwise while stirring under ice cooling, followed by stirring at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, a 10% aqueous sodium hydroxide solution was added to the residue, and the mixture was extracted with benzene. After washing the benzene layer with water and drying, the solvent was distilled off under reduced pressure and the residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain a pale yellow oily substance N-2-indanyl-N-2-(N 1.2 g of -methyl-N-tetrahydrofurfurylamino)ethyl-2,5-dimethoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 27 H 36 N 2 O 4 C% H% N% Theoretical value 71.65 8.02 6.19 Actual value 71.49 8.98 6.29 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.5-4.0 (m, 23H), 3.76 (s, s, 3H,
3H), 6.7-7.4 (m, 7H) Example 8 N-2-indanyl-N'-methyl-N'-cyclopropylmethylethylenediamine 5.0g, triethylamine 5ml, 4-(N・N-dimethylamino)pyridine 50mg Dissolve in 50ml of methylene chloride,
A solution of 7.3 g of 3,4-dimethoxyphenyl acetic acid chloride in 30 ml of methylene chloride was added dropwise to this solution, and the mixture was reacted for 1 hour under ice cooling, and then for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, a 10% aqueous sodium hydroxide solution was added to the residue, and the mixture was extracted with ether. The ether layer is washed with water, dried, and then concentrated under reduced pressure. The residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain N-2-indanyl-N-2-(N-methyl-N-cyclopropylmethylamino)ethyl-3,4- as a pale yellow oil. 4.3 g of dimethoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 26 H 34 N 2 O 3 C% H% N% Theoretical value 73.90 8.11 6.63 Actual value 73.99 8.10 6.81 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0~1.0 (m, 5H), 2.0~4.0 (m, 16H),
3.83 (s, s, 3H, 3H), 6.55-7.35 (m,
7H) Example 9 5 g of N-2-indanyl-N'-methyl-N'-cyclopropylmethylethylenediamine, 5 ml of triethylamine, and 30 mg of 4-(N·N-dimethylamino)pyridine were dissolved in 30 ml of methylene chloride,
A solution of 7.7 g of 2-methoxyphenyl acetic acid chloride in 20 ml of methylene chloride was added dropwise to this solution while stirring under ice cooling, and the mixture was allowed to react for 30 minutes under ice cooling, and for 2 hours at room temperature. The reaction solution was concentrated under reduced pressure, a 10% aqueous sodium hydroxide solution was added to the residue, and the mixture was extracted with ether. The ether layer is washed with water, dried, and then concentrated under reduced pressure. The residue was purified by alumina column chromatography (benzene-ethyl acetate) to give N-2-indanyl-N
3.7 g of -2-(N-methyl-N-cyclopropylmethylamino)ethyl-2-methoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 25 H 32 N 2 O 2 C% H% N% Theoretical value 76.49 8.22 7.14 Actual value 76.60 8.33 7.31 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0-1.0 (m, 5H), 2.0-3.95 (m,
16H), 3.73 (s, 3H), 6.65-7.45 (m,
8H) Example 10 N-2-indanyl-N'-methyl-N'-tetrahydrofurfurylethylenediamine 5.5
A solution of 6 g of phenylacetic acid chloride in 10 ml of methylene chloride is added dropwise to this solution under ice-cooling and stirring.
After reacting for 30 minutes under ice cooling, the mixture was allowed to react for 2 hours at room temperature. Concentrate the reaction solution under reduced pressure to give a residue of 10%.
Add aqueous sodium hydroxide solution and extract with ether.
The ether layer is washed with water, dried, and then concentrated under reduced pressure. The residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain N-2-indanyl-N-2-(N-methyl-
4.3 g of tetrahydrofurfurylamino)ethylphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1640 cm -1 Elemental analysis value C 25 H 32 N 2 O 2 C% H% N% Theoretical value 76.49 8.22 7.14 Actual value 76.50 8.28 7.24 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.0-4.2 (m, 23H), 6.7-7.7 (m, 9H) Example 11 N-2-indanyl-N'-methyl-N'-tetrahydrofurfurylethylenediamine 5.5
g, 5 ml of triethylamine, and 50 mg of 4-(N·N-dimethylamino)pyridine were dissolved in 50 ml of methylene chloride, and to this solution was added 8.5 g of 4-n-propoxyphenylacetic acid chloride in methylene chloride under stirring under ice cooling.
Add 20ml solution dropwise. React for 30 minutes under ice cooling and then for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, a 10% aqueous sodium hydroxide solution was added to the residue, and the mixture was extracted with ether. The ether layer was washed with water and dried, concentrated under reduced pressure, and the residue was purified by alumina column chromatography (benzene-ethyl acetate) to obtain N-2-indanyl-N-2-(N-methyl) as a pale yellow oil. -N-tetrahydrofurfurylamino)
5.3 g of ethyl-4-n-propoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1635 cm -1 Elemental analysis value C 28 H 38 N 2 O 3 C% H% N% Theoretical value 74.63 8.50 6.22 Actual value 74.71 8.43 6.21 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 0.9-4.15 (m, 27H), 1.05 (t, 3H),
6.6-7.4 (m, 8H) Example 12 6 g of N-1-indanylmethyl-N'/N'-diethylethylenediamine, 5 g of 4-methoxyphenylacetic acid, and 4.6 g of phosphorus oxychloride were added to 50 ml of benzene.
Dissolve in and heat under reflux for 2 hours. Cool the reaction solution 10
% aqueous sodium hydroxide solution and separate the benzene layer, wash with water and dry. The solvent was distilled off under reduced pressure, and the residue was distilled under reduced pressure (250-254°C/0.5 mmHg) to give N-1-indanylmethyl-N-2- as a pale yellow oil.
7.3 g of (N.N-diethylamino)ethyl-4-methoxyphenylacetamide are obtained. Infrared absorption spectrum (liquid film) νCO: 1635 cm -1 Elemental analysis value C 25 H 34 N 2 O 2 C% H% N% Theoretical value 76.10 8.69 7.10 Actual value 76.25 8.60 7.10 Nuclear magnetic resonance spectrum (CDCl 3 ) δ: 1.0 (t, t, 3H, 3H), 1.55-4.0 (m,
17H), 3.77 (s, 3H), 6.67-7.35 (m,
8H) Example 13 N-(1,2,3,4-tetrahydro-1-
naphthylmethyl)-N-2-(N-methyl-N-tetrahydrofurfurylamino)ethyl-4-
0.5g of methoxyphenylacetamide in ether
Dissolve in 20 ml and blow an appropriate amount of hydrochloric acid gas into this solution. When the reaction solution is concentrated under reduced pressure, colorless and transparent N is produced.
-(1,2,3,4-tetrahydro-1-naphthylmethyl)-N-2-(N-methyl-N-tetrahydrofurfurylamino)ethyl-4-methoxyphenylacetamide hydrochloride 0.5 g. obtain.
Claims (1)
り、R1は炭素数１〜３のアルキル基であり、R2
は炭素数１〜３のアルキル基、炭素数３〜６の直
鎖状または分枝状のアルケニル基、炭素数４〜７
のシクロアルキルアルキル基またはテトラハイド
ロフルフリール基であり、ｎは０〜２の整数であ
り、ｍは０または１であり、ｌは３〜５の整数で
ある）で表わされるフエニルアセトアミド誘導体
およびそれらの薬理学的に許容できる塩。 ２ 一般式 （式中のＸ、R1、R2およびｎは前記と同じ意味を
もつ）で表わされる特許請求の範囲第１項記載の
フエニルアセトアミド誘導体。 ３ 一般式 （式中のＸ、R1、R2およびｎは前記と同じ意味を
もつ）で表わされる特許請求の範囲第１項記載の
フエニルアセトアミド誘導体。 ４ 一般式 （式中のＸ、R1、R2およびｎは前記と同じ意味を
もつ）で表わされる特許請求の範囲第１項記載の
フエニルアセトアミド誘導体。 ５ 一般式 （式中のＸ、R1、R2およびｎは前記と同じ意味を
もつ）で表わされる特許請求の範囲第１項記載の
フエニルアセトアミド誘導体。 ６ 式 で表わされる特許請求の範囲第２項記載のフエニ
ルアセトアミド誘導体。 ７ 式 で表わされる特許請求の範囲第３項記載のフエニ
ルアセトアミド誘導体。 ８ 式 で表わされる特許請求の範囲第３項記載のフエニ
ルアセトアミド誘導体。 ９ 式 で表わされる特許請求の範囲第３項記載のフエニ
ルアセトアミド誘導体。 １０ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １１ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １２ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １３ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １４ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １５ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １６ 式 で表わされる特許請求の範囲第４項記載のフエニ
ルアセトアミド誘導体。 １７ 式 で表わされる特許請求の範囲第５項記載のフエニ
ルアセトアミド誘導体。[Claims] 1. General formula (X in the formula is an alkoxy group having 1 to 3 carbon atoms, R 1 is an alkyl group having 1 to 3 carbon atoms, and R 2
is an alkyl group having 1 to 3 carbon atoms, a linear or branched alkenyl group having 3 to 6 carbon atoms, and a linear or branched alkenyl group having 4 to 7 carbon atoms.
a cycloalkylalkyl group or a tetrahydrofurfuryl group, n is an integer of 0 to 2, m is 0 or 1, and l is an integer of 3 to 5). and pharmacologically acceptable salts thereof. 2 General formula The phenylacetamide derivative according to claim 1, represented by the formula (X, R 1 , R 2 and n have the same meanings as above). 3 General formula The phenylacetamide derivative according to claim 1, represented by the formula (X, R 1 , R 2 and n have the same meanings as above). 4 General formula The phenylacetamide derivative according to claim 1, represented by the formula (X, R 1 , R 2 and n have the same meanings as above). 5 General formula The phenylacetamide derivative according to claim 1, represented by the formula (X, R 1 , R 2 and n have the same meanings as above). 6 formula The phenylacetamide derivative according to claim 2, which is represented by: 7 formula The phenylacetamide derivative according to claim 3, which is represented by: 8 formula The phenylacetamide derivative according to claim 3, which is represented by: 9 formula The phenylacetamide derivative according to claim 3, which is represented by: 10 formula The phenylacetamide derivative according to claim 4, which is represented by: 11 formula The phenylacetamide derivative according to claim 4, which is represented by: 12 formula The phenylacetamide derivative according to claim 4, which is represented by: 13 formula The phenylacetamide derivative according to claim 4, which is represented by: 14 formula The phenylacetamide derivative according to claim 4, which is represented by: 15 formula The phenylacetamide derivative according to claim 4, which is represented by: 16 formula The phenylacetamide derivative according to claim 4, which is represented by: 17 formula The phenylacetamide derivative according to claim 5, which is represented by:
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4073579A JPS55162760A (en) | 1979-04-04 | 1979-04-04 | Phenylacetamide derivative |
| EP80300817A EP0017376A1 (en) | 1979-03-30 | 1980-03-18 | Phenylacetamide compounds and an analgesic composition containing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4073579A JPS55162760A (en) | 1979-04-04 | 1979-04-04 | Phenylacetamide derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55162760A JPS55162760A (en) | 1980-12-18 |
| JPS6155498B2 true JPS6155498B2 (en) | 1986-11-28 |
Family
ID=12588883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4073579A Granted JPS55162760A (en) | 1979-03-30 | 1979-04-04 | Phenylacetamide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55162760A (en) |
-
1979
- 1979-04-04 JP JP4073579A patent/JPS55162760A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55162760A (en) | 1980-12-18 |
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