CS222700B2 - Method of making the phenylchinolizidine - Google Patents

Method of making the phenylchinolizidine Download PDF

Info

Publication number: CS222700B2
Authority: CS; Czechoslovakia
Prior art keywords: formula; rac; compounds; hydrogen; acids
Prior art date: 1980-04-11

Application number

CS818809A

Other languages

Czech (cs)

English (en)

Inventor

Rene Imhof

Emilio Kyburz

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.)

1980-04-11

Filing date

1981-04-13

Publication date

1983-07-29

1981-04-13 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1983-07-29 Publication of CS222700B2 publication Critical patent/CS222700B2/cs

Links

238000004519 manufacturing process Methods 0.000 title claims 2
OUZYKKYJPBLWGM-UHFFFAOYSA-N 1-phenyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizine Chemical compound C12CCCCN2CCCC1C1=CC=CC=C1 OUZYKKYJPBLWGM-UHFFFAOYSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 20
-1 - iodo Chemical group 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
239000007858 starting material Substances 0.000 claims description 11
238000000034 method Methods 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
150000007513 acids Chemical class 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
239000002131 composite material Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
238000002360 preparation method Methods 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
102100036345 Calicin Human genes 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
101000714682 Homo sapiens Calicin Proteins 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000004093 cyano group Chemical group *C#N 0.000 claims 1
229910052731 fluorine Inorganic materials 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
239000011630 iodine Substances 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
239000000047 product Substances 0.000 description 7
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235000019759 Maize starch Nutrition 0.000 description 6
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239000008101 lactose Substances 0.000 description 6
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235000019341 magnesium sulphate Nutrition 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
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150000003077 polyols Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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239000013543 active substance Substances 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000008298 dragée Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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239000012074 organic phase Substances 0.000 description 3
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239000012071 phase Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
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125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
159000000007 calcium salts Chemical class 0.000 description 2
HTPHKKKMEABKJE-UHFFFAOYSA-N calcium;octadecanoic acid Chemical compound [Ca].CCCCCCCCCCCCCCCCCC(O)=O HTPHKKKMEABKJE-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
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150000002576 ketones Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
SWEBHDISSSNFFL-UHFFFAOYSA-N methyl 7-(2-fluorophenyl)-2-oxo-3,4,6,7,8,9-hexahydroquinolizine-1-carboxylate Chemical compound C1N2CCC(=O)C(C(=O)OC)=C2CCC1C1=CC=CC=C1F SWEBHDISSSNFFL-UHFFFAOYSA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
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150000007524 organic acids Chemical class 0.000 description 2
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150000002923 oximes Chemical class 0.000 description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
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BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
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238000000159 protein binding assay Methods 0.000 description 1
LJPZHJUSICYOIX-UHFFFAOYSA-N quinolizidine Chemical class C1CCCC2CCCCN21 LJPZHJUSICYOIX-UHFFFAOYSA-N 0.000 description 1
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239000003381 stabilizer Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CS818809A 1980-04-11 1981-04-13 Method of making the phenylchinolizidine CS222700B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH278480		1980-04-11

Publications (1)

Publication Number	Publication Date
CS222700B2 true CS222700B2 (en)	1983-07-29

Family

ID=4241517

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS818809A CS222700B2 (en)	1980-04-11	1981-04-13	Method of making the phenylchinolizidine

Country Status (7)

Country	Link
JP (1)	JPS56158783A (es)
KR (1)	KR830005219A (es)
BR (1)	BR8102218A (es)
CS (1)	CS222700B2 (es)
ES (4)	ES8302707A1 (es)
GR (1)	GR74868B (es)
ZA (1)	ZA812285B (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP3737680A1 (en) *	2018-01-08	2020-11-18	F. Hoffmann-La Roche AG	Octahydropyrido[1,2-alpha]pyrazines as magl inhibitors

1981
- 1981-04-03 ZA ZA00812285A patent/ZA812285B/xx unknown
- 1981-04-08 JP JP5189681A patent/JPS56158783A/ja active Pending
- 1981-04-09 GR GR64631A patent/GR74868B/el unknown
- 1981-04-10 BR BR8102218A patent/BR8102218A/pt unknown
- 1981-04-10 KR KR1019810001230A patent/KR830005219A/ko not_active Withdrawn
- 1981-04-13 CS CS818809A patent/CS222700B2/cs unknown
1982
- 1982-05-11 ES ES512073A patent/ES8302707A1/es not_active Expired
- 1982-05-11 ES ES512071A patent/ES8302703A1/es not_active Expired
- 1982-05-11 ES ES512072A patent/ES512072A0/es active Granted
- 1982-05-11 ES ES512074A patent/ES8302704A1/es not_active Expired

Also Published As

Publication number	Publication date
BR8102218A (pt)	1981-10-13
ES512073A0 (es)	1983-02-01
ES512071A0 (es)	1983-02-01
KR830005219A (ko)	1983-08-03
ES512074A0 (es)	1983-02-01
JPS56158783A (en)	1981-12-07
ES8302704A1 (es)	1983-02-01
ZA812285B (en)	1982-04-28
ES8302703A1 (es)	1983-02-01
ES8302706A1 (es)	1983-02-01
ES8302707A1 (es)	1983-02-01
ES512072A0 (es)	1983-02-01
GR74868B (es)	1984-07-12

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