CA1064927A - Procede pour la production de derives de la 2-indenyloxymethymorpholine - Google Patents

Procede pour la production de derives de la 2-indenyloxymethymorpholine

Info

Publication number: CA1064927A
Authority: CA; Canada
Prior art keywords: indenyloxymethyl; morpholine; methyl; solution; mixture
Prior art date: 1975-01-29
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

Application number

CA242,929A

Other languages

English (en)

Inventor

Yuji Kawashima

Shiro Tachikawa

Yoshihisa Nozaki

Masuo Murakami

Soichi Kagami

Kozo Takahashi

Shinji Usuda

Tadao Kojima

Takashi Fujikura

Kunihiro Niigata

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Yamanouchi Pharmaceutical Co Ltd

Original Assignee

Yamanouchi Pharmaceutical Co Ltd

Priority date (The priority date 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 date listed.)

1975-01-29

Filing date

1976-01-05

Publication date

1979-10-23

1975-01-29 Priority claimed from JP50012177A external-priority patent/JPS5188972A/ja

1975-12-25 Priority claimed from JP15564775A external-priority patent/JPS5278883A/ja

1976-01-05 Application filed by Yamanouchi Pharmaceutical Co Ltd filed Critical Yamanouchi Pharmaceutical Co Ltd

1979-10-23 Application granted granted Critical

1979-10-23 Publication of CA1064927A publication Critical patent/CA1064927A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 26
MMLSVAZDIYUZKQ-UHFFFAOYSA-N 2-(1h-inden-1-yloxymethyl)morpholine Chemical class C1=CC2=CC=CC=C2C1OCC1CNCCO1 MMLSVAZDIYUZKQ-UHFFFAOYSA-N 0.000 title claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 61
-1 haloacetyl halide Chemical class 0.000 claims description 40
239000003795 chemical substances by application Substances 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 7
XCSZTYWLSGOSGZ-UHFFFAOYSA-N 2-(3h-inden-4-yloxymethyl)-4-propylmorpholine Chemical compound C1N(CCC)CCOC1COC1=CC=CC2=C1CC=C2 XCSZTYWLSGOSGZ-UHFFFAOYSA-N 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
XNZFWJZKEDAOEO-UHFFFAOYSA-N 2-[(1-methyl-3h-inden-4-yl)oxymethyl]morpholine Chemical compound CC1=CCC2=C1C=CC=C2OCC1CNCCO1 XNZFWJZKEDAOEO-UHFFFAOYSA-N 0.000 claims description 4
GCODTPFPXJDRBB-UHFFFAOYSA-N 2-[(3-methyl-1h-inden-4-yl)oxymethyl]-4-propan-2-ylmorpholine Chemical compound C1N(C(C)C)CCOC1COC1=CC=CC2=C1C(C)=CC2 GCODTPFPXJDRBB-UHFFFAOYSA-N 0.000 claims description 4
NQGZTPHYLCNJRP-UHFFFAOYSA-N 4-ethyl-2-(3h-inden-4-yloxymethyl)morpholine Chemical compound C1N(CC)CCOC1COC1=CC=CC2=C1CC=C2 NQGZTPHYLCNJRP-UHFFFAOYSA-N 0.000 claims description 4
MADRVGBADLFHMO-UHFFFAOYSA-N Indeloxazine Chemical compound C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 MADRVGBADLFHMO-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
229910052987 metal hydride Inorganic materials 0.000 claims description 4
BCHMLZGUIOOLMB-UHFFFAOYSA-N 4-butyl-2-(3h-inden-4-yloxymethyl)morpholine Chemical compound C1N(CCCC)CCOC1COC1=CC=CC2=C1CC=C2 BCHMLZGUIOOLMB-UHFFFAOYSA-N 0.000 claims description 3
238000010438 heat treatment Methods 0.000 claims description 3
150000004681 metal hydrides Chemical class 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
238000007363 ring formation reaction Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
BTANJTPOVYQNRW-UHFFFAOYSA-N 2-(3h-inden-4-yloxymethyl)-4-propan-2-ylmorpholine Chemical compound C1N(C(C)C)CCOC1COC1=CC=CC2=C1CC=C2 BTANJTPOVYQNRW-UHFFFAOYSA-N 0.000 claims 2
USJWEKQRLIWATG-UHFFFAOYSA-N 2-[(1-methyl-3h-inden-4-yl)oxymethyl]-4-propan-2-ylmorpholine Chemical compound C1N(C(C)C)CCOC1COC1=CC=CC2=C1CC=C2C USJWEKQRLIWATG-UHFFFAOYSA-N 0.000 claims 2
RHRBHVPZBPQWFS-UHFFFAOYSA-N 1-amino-4-(1h-inden-1-yloxy)butan-2-ol Chemical class C1=CC=C2C(OCCC(O)CN)C=CC2=C1 RHRBHVPZBPQWFS-UHFFFAOYSA-N 0.000 claims 1
150000002431 hydrogen Chemical group 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 11
229960001252 methamphetamine Drugs 0.000 abstract description 7
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 abstract description 7
230000001965 increasing effect Effects 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
239000000243 solution Substances 0.000 description 117
239000000203 mixture Substances 0.000 description 90
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
229940093499 ethyl acetate Drugs 0.000 description 52
235000019439 ethyl acetate Nutrition 0.000 description 52
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
238000000921 elemental analysis Methods 0.000 description 41
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
238000003756 stirring Methods 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
229960001701 chloroform Drugs 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 32
239000002904 solvent Substances 0.000 description 30
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
239000000047 product Substances 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
101150041968 CDC13 gene Proteins 0.000 description 25
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
238000001816 cooling Methods 0.000 description 25
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 25
238000002844 melting Methods 0.000 description 22
230000008018 melting Effects 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000012280 lithium aluminium hydride Substances 0.000 description 21
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 20
235000011167 hydrochloric acid Nutrition 0.000 description 19
229960000443 hydrochloric acid Drugs 0.000 description 19
229940076134 benzene Drugs 0.000 description 18
235000013350 formula milk Nutrition 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
229940113083 morpholine Drugs 0.000 description 15
241000699670 Mus sp. Species 0.000 description 13
229940086542 triethylamine Drugs 0.000 description 12
239000002253 acid Substances 0.000 description 11
238000010898 silica gel chromatography Methods 0.000 description 11
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
239000013078 crystal Substances 0.000 description 10
229910052708 sodium Inorganic materials 0.000 description 10
239000011734 sodium Substances 0.000 description 10
239000008096 xylene Substances 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
229940022682 acetone Drugs 0.000 description 9
239000000725 suspension Substances 0.000 description 9
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 7
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000010410 layer Substances 0.000 description 7
YWPHCCPCQOJSGZ-UHFFFAOYSA-N 2-[(2-ethoxyphenoxy)methyl]morpholine Chemical compound CCOC1=CC=CC=C1OCC1OCCNC1 YWPHCCPCQOJSGZ-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
229940073584 methylene chloride Drugs 0.000 description 6
238000001228 spectrum Methods 0.000 description 6
229960001255 viloxazine Drugs 0.000 description 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
206010015995 Eyelid ptosis Diseases 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 4
QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 4
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
235000015165 citric acid Nutrition 0.000 description 4
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
235000001055 magnesium Nutrition 0.000 description 4
229940091250 magnesium supplement Drugs 0.000 description 4
238000002156 mixing Methods 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 4
229960003147 reserpine Drugs 0.000 description 4
MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 4
239000003826 tablet Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
HRZOZBACGNOSRE-UHFFFAOYSA-N 6-[(1-oxo-2,3-dihydroinden-5-yl)oxymethyl]-4-propan-2-ylmorpholin-3-one Chemical compound O1CC(=O)N(C(C)C)CC1COC1=CC=C(C(=O)CC2)C2=C1 HRZOZBACGNOSRE-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 3
229960000836 amitriptyline Drugs 0.000 description 3
230000000891 anti-reserpine Effects 0.000 description 3
230000006399 behavior Effects 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
201000003004 ptosis Diseases 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
238000005303 weighing Methods 0.000 description 3
SGCZBGPWADOMLF-UHFFFAOYSA-N 1-methyl-7-[(4-propan-2-ylmorpholin-2-yl)methoxy]-2,3-dihydroinden-1-ol Chemical compound C1N(C(C)C)CCOC1COC1=CC=CC2=C1C(C)(O)CC2 SGCZBGPWADOMLF-UHFFFAOYSA-N 0.000 description 2
DPHNJPUOMLRELT-UHFFFAOYSA-N 2,3-dihydro-1h-inden-4-ol Chemical compound OC1=CC=CC2=C1CCC2 DPHNJPUOMLRELT-UHFFFAOYSA-N 0.000 description 2
RHJCDXFCUVOILU-UHFFFAOYSA-N 2-(1h-inden-4-yloxymethyl)morpholine;hydrochloride Chemical compound Cl.C=1C=CC=2CC=CC=2C=1OCC1CNCCO1 RHJCDXFCUVOILU-UHFFFAOYSA-N 0.000 description 2
DLKSVCYOIXWZDQ-UHFFFAOYSA-N 2-(1h-inden-5-yloxymethyl)-4-propan-2-ylmorpholine Chemical compound C1N(C(C)C)CCOC1COC1=CC=C(CC=C2)C2=C1 DLKSVCYOIXWZDQ-UHFFFAOYSA-N 0.000 description 2
ZOELNOZIEANIGU-UHFFFAOYSA-N 2-(3h-inden-4-yloxymethyl)-4-methylmorpholine Chemical compound C1N(C)CCOC1COC1=CC=CC2=C1CC=C2 ZOELNOZIEANIGU-UHFFFAOYSA-N 0.000 description 2
SYZRZLUNWVNNNV-UHFFFAOYSA-N 2-bromoacetyl chloride Chemical compound ClC(=O)CBr SYZRZLUNWVNNNV-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
QKFGWTLXRUFHOY-UHFFFAOYSA-N 3-methyl-5-[(4-propan-2-ylmorpholin-2-yl)methoxy]-2,3-dihydro-1h-inden-1-ol Chemical compound C1N(C(C)C)CCOC1COC1=CC=C(C(O)CC2C)C2=C1 QKFGWTLXRUFHOY-UHFFFAOYSA-N 0.000 description 2
LKSJUXIZTGZHNQ-UHFFFAOYSA-N 4-(morpholin-2-ylmethoxy)-2,3-dihydro-1h-inden-1-ol Chemical compound OC1CCC2=C1C=CC=C2OCC1CNCCO1 LKSJUXIZTGZHNQ-UHFFFAOYSA-N 0.000 description 2
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238000007796 conventional method Methods 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
238000013508 migration Methods 0.000 description 1
230000005012 migration Effects 0.000 description 1
150000002780 morpholines Chemical class 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000036647 reaction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
229940116269 uric acid Drugs 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA242,929A 1975-01-29 1976-01-05 Procede pour la production de derives de la 2-indenyloxymethymorpholine Expired CA1064927A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP50012177A JPS5188972A (en)	1975-01-29	1975-01-29	2277 indeniruokishimechiru *4 chikanmoruhorinjudotainoseiho
JP15564775A JPS5278883A (en)	1975-12-25	1975-12-25	Synthesis of novel indene derivatives

Publications (1)

Publication Number	Publication Date
CA1064927A true CA1064927A (fr)	1979-10-23

Family

ID=26347750

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA242,929A Expired CA1064927A (fr)	1975-01-29	1976-01-05	Procede pour la production de derives de la 2-indenyloxymethymorpholine

Country Status (5)

Country	Link
CA (1)	CA1064927A (fr)
DE (1)	DE2601703C2 (fr)
DK (1)	DK143846C (fr)
GB (1)	GB1535276A (fr)
SE (1)	SE424550B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL56369A (en) *	1978-01-20	1984-05-31	Erba Farmitalia	Alpha-phenoxybenzyl propanolamine derivatives,their preparation and pharmaceutical compositions comprising them
RU2123496C1 (ru) *	1993-02-10	1998-12-20	Яманоути Фармасьютикал Ко., Лтд.	Производное морфолина или его фармацевтически приемлемая соль и фармацевтическая композиция на его основе

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE299970C (fr) *
GB1138405A (en) *	1966-12-28	1969-01-01	Ici Ltd	Morpholine derivatives
GB1382526A (en) *	1972-08-11	1975-02-05	Ici Ltd	Morpholine derivatives

1976
- 1976-01-05 CA CA242,929A patent/CA1064927A/fr not_active Expired
- 1976-01-16 GB GB176276A patent/GB1535276A/en not_active Expired
- 1976-01-19 DE DE19762601703 patent/DE2601703C2/de not_active Expired
- 1976-01-28 DK DK35276A patent/DK143846C/da not_active IP Right Cessation
- 1976-01-28 SE SE7600894A patent/SE424550B/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
GB1535276A (en)	1978-12-13
SE424550B (sv)	1982-07-26
SE7600894L (sv)	1976-07-30
DE2601703A1 (de)	1976-08-05
DE2601703C2 (de)	1985-06-27
DK143846C (da)	1982-04-13
DK143846B (da)	1981-10-19
DK35276A (da)	1976-07-30

Publication	Publication Date	Title
US4820873A (en)	1989-04-11	Pyrene derivatives
KR880001315B1 (ko)	1988-07-23	4-아미노-6, 7-디메톡시퀴놀린 유도체의 제조방법
Barluenga et al.	1995	Stereoselective synthesis of seven-membered carbocycles from 2-amino-1, 3-butadienes and vinyl chromium Fischer-type carbenes
JP2617546B2 (ja)	1997-06-04	３‐〔４（１‐置換‐４‐ピペラジニル）ブチル〕‐４‐チアゾリジノンおよびその製法
RU2159228C2 (ru)	2000-11-20	Производные замещенного бензамидина
CA2135861A1 (fr)	1995-06-14	Derives de l'oxazolidine-2-one
CA1273929A (fr)	1990-09-11	N-(piperidinylaklyl) carboxamides
HU192975B (en)	1987-08-28	Process for preparing pyridazine derivatives with psychotropic activity
AU618626B2 (en)	1992-01-02	New benzoxazolinone derivatives, processes for the preparation thereof and pharmaceutical compositions containing them
CA1146563A (fr)	1983-05-17	Derives de benzimidazole; preparation et applications; compositions qui en renferment
KR20230058132A (ko)	2023-05-02	Gpr52 조절인자 화합물
US4109088A (en)	1978-08-22	2-(indenyloxymethyl) morpholine derivatives
JPH0471072B2 (fr)	1992-11-12
Aloup et al.	1987	Synthesis and antisecretory and antiulcer activities of derivatives and analogs of 2-(2-pyridyl) tetrahydrothiophene-2-carbothioamide
EP0835254A1 (fr)	1998-04-15	Derives d'oxazolidinone, leur preparation et leur application en therapeutique
CN1100759C (zh)	2003-02-05	呫吨和吖啶衍生物及其用途
EP0077536B1 (fr)	1986-07-16	Spiro(benzofuranne-2(3H),1'-cycloalcanes) substitués en 2', procédé pour leur préparation, compositions pharmaceutiques les contenant et leur utilisation comme médicaments
JPH01156966A (ja)	1989-06-20	リポキシゲナーゼ抑制作用を有するピリダジノン、トリアジノンおよびオキサピリダジノン化合物
NL8201969A (nl)	1982-12-01	1-aminoderivaten van 1-(3',4-methyleendioxyfenyl)propan-2-ol, alsmede werkwijze voor hun bereiding.
JPS6159308B2 (fr)	1986-12-16
Barluenga et al.	1983	Regiospecific synthesis of isoxazoles by reaction of 1-azabutadiene derivatives with hydroxylamine hydrochloride
Dillard et al.	1966	Acetylenic Amines. XI. Cyclizations of 3-Substituted N-(β-Hydroxyethyl)-1, 1-dialkyl-2-propynylamines
de Andrade et al.	2024	Synthesis and anti-bacterial activity evaluation against Mycobacterium tuberculosis of new quinoline derivatives coupled with the camphor nucleus
EP1446390B1 (fr)	2009-12-02	Composes d'oxazine photochromes et leurs procedes de fabrication
JPS62209047A (ja)	1987-09-14	光学活性β−アミノアルコ−ルの製造方法