DK168069B1 - Isoquinolinderivater og en fremgangsmaade til fremstilling af octahydroisoquinoliner ud fra derivaterne - Google Patents

Isoquinolinderivater og en fremgangsmaade til fremstilling af octahydroisoquinoliner ud fra derivaterne Download PDF

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Publication number: DK168069B1
Authority: DK; Denmark
Prior art keywords: formula; lower alkyl; approx; aryl; lower alkoxy
Prior art date: 1987-11-11

Application number

DK584488A

Other languages

Danish (da)

English (en)

Other versions

DK584488D0 (da

DK584488A (da

Inventor

Emil Albin Broger

Yvo Crameri

Bernd Heiser

Original Assignee

Hoffmann La Roche

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.)

1987-11-11

Filing date

1988-10-20

Publication date

1994-01-31

1988-10-20 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1988-10-20 Publication of DK584488D0 publication Critical patent/DK584488D0/da

1989-05-12 Publication of DK584488A publication Critical patent/DK584488A/da

1994-01-31 Application granted granted Critical

1994-01-31 Publication of DK168069B1 publication Critical patent/DK168069B1/da

Links

238000000034 method Methods 0.000 title claims description 3
238000002360 preparation method Methods 0.000 title description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims abstract description 33
125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
125000003118 aryl group Chemical group 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract description 4
239000003054 catalyst Substances 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 9
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 7
238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
229910052707 ruthenium Inorganic materials 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
GXGJIOMUZAGVEH-UHFFFAOYSA-N Chamazulene Chemical group CCC1=CC=C(C)C2=CC=C(C)C2=C1 GXGJIOMUZAGVEH-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
239000000543 intermediate Substances 0.000 abstract description 2
INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 abstract description 2
229940051807 opiod analgesics morphinan derivative Drugs 0.000 abstract description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
239000003446 ligand Substances 0.000 description 16
-1 e.g. Chemical group 0.000 description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
150000001875 compounds Chemical class 0.000 description 11
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000000203 mixture Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
BZRZRYUSZDFEJD-CPNJWEJPSA-N 1-[(1e)-1-[(4-methoxyphenyl)methylidene]-3,4,5,6,7,8-hexahydroisoquinolin-2-yl]ethanone Chemical compound C1=CC(OC)=CC=C1\C=C\1C(CCCC2)=C2CCN/1C(C)=O BZRZRYUSZDFEJD-CPNJWEJPSA-N 0.000 description 8
239000012300 argon atmosphere Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 8
239000013078 crystal Substances 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
WHLQQRGHOPIIMQ-UHFFFAOYSA-N [2-(2-diphenylphosphanyl-6-methylphenyl)-3-methylphenyl]-diphenylphosphane Chemical compound CC=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=1C(C)=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 WHLQQRGHOPIIMQ-UHFFFAOYSA-N 0.000 description 6
VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 6
239000005457 ice water Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
GCZLLCQUVMHZCQ-UHFFFAOYSA-N 1-[1-[(4-methoxyphenyl)methyl]-4,6,7,8-tetrahydro-3h-isoquinolin-2-yl]ethanone Chemical compound C1=CC(OC)=CC=C1CC(N(CC1)C(C)=O)=C2C1=CCCC2 GCZLLCQUVMHZCQ-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000004912 1,5-cyclooctadiene Substances 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
238000006317 isomerization reaction Methods 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
YPXQKKBSILHWOE-IBGZPJMESA-N 1-[(1s)-1-[(4-methoxyphenyl)methyl]-3,4,5,6,7,8-hexahydro-1h-isoquinolin-2-yl]ethanone Chemical compound C1=CC(OC)=CC=C1C[C@H]1C(CCCC2)=C2CCN1C(C)=O YPXQKKBSILHWOE-IBGZPJMESA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
229910000831 Steel Inorganic materials 0.000 description 3
239000000538 analytical sample Substances 0.000 description 3
150000001450 anions Chemical class 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
238000004817 gas chromatography Methods 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
239000000047 product Substances 0.000 description 3
150000003303 ruthenium Chemical class 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000010959 steel Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
239000012327 Ruthenium complex Substances 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
RBYGDVHOECIAFC-UHFFFAOYSA-L acetonitrile;palladium(2+);dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CC#N.CC#N RBYGDVHOECIAFC-UHFFFAOYSA-L 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
HDULBKVLSJEMGN-UHFFFAOYSA-N dicyclohexylphosphane Chemical compound C1CCCCC1PC1CCCCC1 HDULBKVLSJEMGN-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000011261 inert gas Substances 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
LRGZZEOWQURWFK-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydroisoquinoline Chemical class C1NCCC2CCCC=C21 LRGZZEOWQURWFK-UHFFFAOYSA-N 0.000 description 1
VJFARDWQCMLCGT-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydroisoquinoline Chemical compound C1C=CC=C2CNCCC21 VJFARDWQCMLCGT-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
IYZRINJHKVQAQC-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-3,4,5,6,7,8-hexahydroisoquinoline Chemical compound C1=CC(OC)=CC=C1CC1=NCCC2=C1CCCC2 IYZRINJHKVQAQC-UHFFFAOYSA-N 0.000 description 1
KJPBHWPECBAAAA-UHFFFAOYSA-N 1-bromo-2-(2-bromo-6-methylphenyl)-3-methylbenzene Chemical group CC1=CC=CC(Br)=C1C1=C(C)C=CC=C1Br KJPBHWPECBAAAA-UHFFFAOYSA-N 0.000 description 1
RUGISKODRCWQNE-UHFFFAOYSA-N 2-(2-methylphenyl)ethanol Chemical compound CC1=CC=CC=C1CCO RUGISKODRCWQNE-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
AOBQMWZNCPVXEM-UHFFFAOYSA-N 3,4,5,6,7,8-hexahydroisoquinoline Chemical compound C1CN=CC2=C1CCCC2 AOBQMWZNCPVXEM-UHFFFAOYSA-N 0.000 description 1
SNKAAIQBOBROQQ-UHFFFAOYSA-N 4,7-dimethylbicyclo[2.2.1]heptane-7-carbonyl chloride Chemical compound C1CC2CCC1(C)C2(C)C(Cl)=O SNKAAIQBOBROQQ-UHFFFAOYSA-N 0.000 description 1
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical class [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
239000004280 Sodium formate Chemical class 0.000 description 1
HKYSIUYOULVHTO-UHFFFAOYSA-N [chloro(cyclohexyl)phosphoryl]cyclohexane Chemical compound C1CCCCC1P(=O)(Cl)C1CCCCC1 HKYSIUYOULVHTO-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
239000008232 de-aerated water Substances 0.000 description 1
229960001985 dextromethorphan Drugs 0.000 description 1
150000001993 dienes Chemical class 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
238000011065 in-situ storage Methods 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
150000002576 ketones Chemical class 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
RYJJRNKXVNLJLO-UHFFFAOYSA-N methyl 1-[(4-methoxyphenyl)methyl]-4,6,7,8-tetrahydro-3h-isoquinoline-2-carboxylate Chemical compound COC(=O)N1CCC2=CCCCC2=C1CC1=CC=C(OC)C=C1 RYJJRNKXVNLJLO-UHFFFAOYSA-N 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000001632 sodium acetate Chemical class 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical class [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
230000032258 transport Effects 0.000 description 1
ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
239000005052 trichlorosilane Substances 0.000 description 1
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
230000007306 turnover Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Catalysts (AREA)

DK584488A 1987-11-11 1988-10-20 Isoquinolinderivater og en fremgangsmaade til fremstilling af octahydroisoquinoliner ud fra derivaterne DK168069B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP87810651		1987-11-11
EP87810651		1987-11-11

Publications (3)

Publication Number	Publication Date
DK584488D0 DK584488D0 (da)	1988-10-20
DK584488A DK584488A (da)	1989-05-12
DK168069B1 true DK168069B1 (da)	1994-01-31

Family

ID=8198427

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK584488A DK168069B1 (da)	1987-11-11	1988-10-20	Isoquinolinderivater og en fremgangsmaade til fremstilling af octahydroisoquinoliner ud fra derivaterne

Country Status (6)

Country	Link
US (1)	US4857648A (ja)
EP (1)	EP0315886B1 (ja)
JP (1)	JP2579677B2 (ja)
AT (1)	ATE118482T1 (ja)
DE (1)	DE3853043T2 (ja)
DK (1)	DK168069B1 (ja)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4791107A (en) *	1986-07-16	1988-12-13	Hoechst-Roussel Pharmaceuticals, Inc.	Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use
DK0397042T3 (da) *	1989-05-10	1995-10-02	Hoffmann La Roche	Fremstilling af isoquinolinderivater
JPH0692427B2 (ja) *	1989-07-11	1994-11-16	高砂香料工業株式会社	２，２’―ビス（ジシクロヘキシルホスフィノ）―６，６’―ジメチル―１，１’―ビフェニルを配位子とする錯体，およびその錯体を用いた有機カルボン酸とそのエステルの製造方法
KR0172971B1 (ko) *	1990-06-27	1999-02-01	문캐로린디	1,2,3,3a,8,8a-헥사히드로-1,3a,8-트리메틸 피롤로[2,3-b]인돌의 테트라히드로 이소퀴놀리닐 카바메이트
AU685820B2 (en) *	1990-06-27	1998-01-29	Hoechst-Roussel Pharmaceuticals Incorporated	Tetrahydroisoquinolinylcarbamates of 1,2,3,3A,8,8A-hexahydro-1,3A,8-trimethylpyrrolo(2,3-B)indole
US5084461A (en) *	1991-03-27	1992-01-28	Merrell Dow Pharmaceuticals Inc.	Azadecalin amides and thioamides as inhibitors of cholesterol biosynthesis
US5350758A (en) *	1992-07-08	1994-09-27	Merrell Dow Pharmaceuticals Inc.	Piperidyl sulfonamides and sulfoxamides as inhibitors of cholesterol biosynthesis
EP0834506B1 (de) *	1996-10-02	2004-01-14	F. Hoffmann-La Roche Ag	Verfahren zur Herstellung von (9alpha, 13alpha, 14alpha)-1-(3-Methoxymorphinan-17-yl)alkanonen
EP0834505B1 (de) *	1996-10-02	2004-01-07	F. Hoffmann-La Roche Ag	Verfahren zur Herstellung von (Z)-1-[1-(4-Methoxybenzyliden)-1,2,3,4,5,6,7,8-octahydro-isochinolin-2-yl]alkanonen
US5905153A (en) *	1996-10-02	1999-05-18	Roche Vitamins Inc.	Process for preparing (9α,13α,14α)-1-(3-methoxy-morphinan-17-yl)alkanones
US5849917A (en) *	1996-10-02	1998-12-15	Roche Vitamins Inc.	Process for the preparation of isoquinoline compounds
DE19706396A1 (de) *	1996-12-09	1998-06-10	Bayer Ag	Verfahren zur Herstellung von 3-(l-Hydroxiphenyl-l-alkoximinomethyl)dioxazinen
US5880285A (en) *	1996-12-23	1999-03-09	Roche Vitamins Inc.	Process for manufacture of optically active isochinole compounds
CN103265489B (zh) *	2013-06-17	2015-03-25	苏州立新制药有限公司	ent-(14S)-3-甲氧基-17-甲基吗喃的制备方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB685750A (en) *	1949-10-14	1953-01-07	Hoffmann La Roche	Improvements in or relating to isoquinoline derivatives
US3634429A (en) *	1969-09-30	1972-01-11	Hoffmann La Roche	Morphinan derivatives and preparation thereof
US4247697A (en) *	1979-09-10	1981-01-27	Hoffmann-La Roche Inc.	3-Phenoxy morphinans and their derivatives
US4514569A (en) *	1982-01-28	1985-04-30	Hendrickson James B	Synthesis of 1-substituted isoquinolines
DE3436179A1 (de) *	1984-10-03	1986-04-10	Merck Patent Gmbh, 6100 Darmstadt	Verfahren zur herstellung optisch aktiver amine
JPS62265266A (ja) *	1986-05-13	1987-11-18	Takasago Corp	Ｎ−アシル−テトラヒドロイソキノリン類の製造法

1988
- 1988-10-20 DK DK584488A patent/DK168069B1/da not_active IP Right Cessation
- 1988-11-02 EP EP88118220A patent/EP0315886B1/en not_active Expired - Lifetime
- 1988-11-02 AT AT88118220T patent/ATE118482T1/de not_active IP Right Cessation
- 1988-11-02 DE DE3853043T patent/DE3853043T2/de not_active Expired - Fee Related
- 1988-11-08 US US07/268,441 patent/US4857648A/en not_active Expired - Lifetime
- 1988-11-10 JP JP63282634A patent/JP2579677B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
US4857648A (en)	1989-08-15
DE3853043T2 (de)	1995-06-08
DK584488D0 (da)	1988-10-20
DK584488A (da)	1989-05-12
JP2579677B2 (ja)	1997-02-05
EP0315886A3 (en)	1990-04-25
DE3853043D1 (de)	1995-03-23
JPH01160965A (ja)	1989-06-23
EP0315886A2 (en)	1989-05-17
EP0315886B1 (en)	1995-02-15
ATE118482T1 (de)	1995-03-15

Publication	Publication Date	Title
DK168069B1 (da)	1994-01-31	Isoquinolinderivater og en fremgangsmaade til fremstilling af octahydroisoquinoliner ud fra derivaterne
Li et al.	2005	Stereocontrolled creation of adjacent quaternary and tertiary stereocenters via a catalytic diastereoselective and enantioselective conjugate addition
US5430191A (en)	1995-07-04	Phosphorus compounds
US4851537A (en)	1989-07-25	Process for preparing N-acyltetrahydroisoquinoline
JPH0320290A (ja)	1991-01-29	２，２’―ビス〔ジー（ｍ―トリル）ホスフィノ〕―１，１’―ビナフチル
US5380861A (en)	1995-01-10	Process for preparing pyridine 2-carboxamides
JP2546830B2 (ja)	1996-10-23	新規なキラルロジウム−ジホスフイン錯体
US4514569A (en)	1985-04-30	Synthesis of 1-substituted isoquinolines
GB2224277A (en)	1990-05-02	Chiral 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and l-phenylalanine derivatives
Kajigaeshi et al.	1990	Halogenation using quaternary ammonium polyhalides. XXIV. Chlorination of acetanilides with benzyltrimethylammonium tetrachloroiodate.
JP2903627B2 (ja)	1999-06-07	イソキノリン誘導体の製造法
JPH07173183A (ja)	1995-07-11	三価のリンの新規環状化合物、それらの製造方法およびそれらの用途
JP2008505903A (ja)	2008-02-28	四置換エナミドの形成およびこの立体選択的還元
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AU2018250840B2 (en)	2021-06-24	Chiral metal complex compounds
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JP2981621B2 (ja)	1999-11-22	ビフェニルビスホスフィン錯体
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Legal Events

Date	Code	Title	Description
1994-01-31	B1	Patent granted (law 1993)
2002-05-27	PBP	Patent lapsed