CA1261336A - Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a|- quinolizine - Google Patents

Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a|- quinolizine

Info

Publication number: CA1261336A
Authority: CA; Canada
Prior art keywords: formula; compound; ethyl; carbon atoms; pharmaceutically acceptable
Prior art date: 1981-06-12
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

CA000580550A

Other languages

English (en)

Inventor

Csaba Szantay

Lajos Szabo

Gyorgy Kalaus

Janos Kreidl

Laszlo Czibula

Gyorgy Visky

Andras Nemes

Maria Farkas

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.)

Richter Gedeon Vegyeszeti Gyar Nyrt

Original Assignee

Richter Gedeon Vegyeszeti Gyar RT

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.)

1981-06-12

Filing date

1988-10-18

Publication date

1989-09-26

1981-06-12 Priority claimed from HU811753A external-priority patent/HU186891B/hu

1988-10-18 Application filed by Richter Gedeon Vegyeszeti Gyar RT filed Critical Richter Gedeon Vegyeszeti Gyar RT

1988-10-18 Priority to CA000580550A priority Critical patent/CA1261336A/fr

1989-09-26 Application granted granted Critical

1989-09-26 Publication of CA1261336A publication Critical patent/CA1261336A/fr

Status Expired legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims abstract description 80
238000000034 method Methods 0.000 claims abstract description 37
239000002253 acid Substances 0.000 claims abstract description 26
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
125000000217 alkyl group Chemical group 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 14
239000002904 solvent Substances 0.000 claims abstract description 13
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 7
150000001340 alkali metals Chemical class 0.000 claims abstract description 7
150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 7
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 47
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 22
239000000203 mixture Substances 0.000 claims description 14
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical group [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical group OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
125000002471 4H-quinolizinyl group Chemical class C=1(C=CCN2C=CC=CC12)* 0.000 claims description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 5
229910052700 potassium Inorganic materials 0.000 claims description 5
239000011591 potassium Substances 0.000 claims description 5
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 claims description 4
229910052708 sodium Inorganic materials 0.000 claims description 4
239000011734 sodium Substances 0.000 claims description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
239000008096 xylene Substances 0.000 claims description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
229940113088 dimethylacetamide Drugs 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 10
239000003085 diluting agent Substances 0.000 claims 5
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 claims 3
NLUITSGZLWUTJO-UHFFFAOYSA-N 1-imino-3,4,6,7,7a,7b-hexahydro-2H-indolo[2,3-a]quinolizin-2-ol Chemical class OC1CCN2CCC3C(=C2C1=N)N=C1C=CC=CC13 NLUITSGZLWUTJO-UHFFFAOYSA-N 0.000 claims 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
238000005809 transesterification reaction Methods 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 8
238000002360 preparation method Methods 0.000 abstract description 6
230000000694 effects Effects 0.000 abstract description 2
PSMSFIJDXQDYTQ-GHMZBOCLSA-N N-[(7aR,7bR)-3,4,6,7,7a,7b-hexahydro-2H-indolo[2,3-a]quinolizin-1-ylidene]hydroxylamine Chemical class C1=CC=CC2=NC3=C4C(=NO)CCCN4CC[C@@H]3[C@H]21 PSMSFIJDXQDYTQ-GHMZBOCLSA-N 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
238000002844 melting Methods 0.000 description 31
230000008018 melting Effects 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
230000000875 corresponding effect Effects 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 8
239000000243 solution Substances 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
ZFCQLDAGNBFMJQ-QUCCMNQESA-N apovincaminic acid Chemical class C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(O)=O)N5C2=C1 ZFCQLDAGNBFMJQ-QUCCMNQESA-N 0.000 description 6
RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
-1 apovincaminic acid ester Chemical class 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003791 organic solvent mixture Substances 0.000 description 4
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000002082 anti-convulsion Effects 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
238000000354 decomposition reaction Methods 0.000 description 3
RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
229960002726 vincamine Drugs 0.000 description 3
229960000744 vinpocetine Drugs 0.000 description 3
OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
241000396377 Tranes Species 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910000102 alkali metal hydride Inorganic materials 0.000 description 2
150000008046 alkali metal hydrides Chemical class 0.000 description 2
238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
230000003266 anti-allergic effect Effects 0.000 description 2
230000000141 anti-hypoxic effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
GUOHRXPYGSKUGT-UHFFFAOYSA-N quinolizinium Chemical class C1=CC=CC2=CC=CC=[N+]21 GUOHRXPYGSKUGT-UHFFFAOYSA-N 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
DXDIHODZARUBLA-DTPOWOMPSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid;hydrate Chemical compound O.O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 DXDIHODZARUBLA-DTPOWOMPSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
OURDZMSSMGUMKR-UHFFFAOYSA-N 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine Chemical class C1=CC=C2C(CCN3CCCCC33)=C3NC2=C1 OURDZMSSMGUMKR-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
SNJHPBCJDWASBR-UHFFFAOYSA-O 1-ethyl-2,3,4,6,7,12-hexahydro-1h-indolo[2,3-a]quinolizin-5-ium Chemical compound N1C2=CC=CC=C2C(CC2)=C1C1=[N+]2CCCC1CC SNJHPBCJDWASBR-UHFFFAOYSA-O 0.000 description 1
UEQPWHMQQVMTIO-UHFFFAOYSA-N 2,3,3a,4,5,6-hexahydro-1H-indol-2-ol Chemical compound N1C(CC2CCCC=C12)O UEQPWHMQQVMTIO-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
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
OZDNDGXASTWERN-CTNGQTDRSA-N Apovincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(=O)OC)N5C2=C1 OZDNDGXASTWERN-CTNGQTDRSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
241000238366 Cephalopoda Species 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 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
WYJAPUKIYAZSEM-MOPGFXCFSA-N Eburnamonine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)CC(=O)N5C2=C1 WYJAPUKIYAZSEM-MOPGFXCFSA-N 0.000 description 1
PSMSFIJDXQDYTQ-UHFFFAOYSA-N N-(3,4,6,7,7a,7b-hexahydro-2H-indolo[2,3-a]quinolizin-1-ylidene)hydroxylamine Chemical class C1=CC=CC2=NC3=C4C(=NO)CCCN4CCC3C21 PSMSFIJDXQDYTQ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UXMCFEBDJVHVNH-HOJAQTOUSA-N ac1l52id Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(O)=O)N5C2=C1 UXMCFEBDJVHVNH-HOJAQTOUSA-N 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000000879 anti-atherosclerotic effect Effects 0.000 description 1
230000001078 anti-cholinergic effect Effects 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000767 anti-ulcer Effects 0.000 description 1
239000003416 antiarrhythmic agent Substances 0.000 description 1
229950006936 apovincamine Drugs 0.000 description 1
OZDNDGXASTWERN-UHFFFAOYSA-N apovincamine Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)C=C(C(=O)OC)N5C2=C1 OZDNDGXASTWERN-UHFFFAOYSA-N 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
229960001270 d- tartaric acid Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000000147 hypnotic effect Effects 0.000 description 1
DBVVQINTNHWWGH-UHFFFAOYSA-N indolo[3,2-a]quinolizine Chemical compound C1=CC=CC2=C3C4=CC=CC=C4N=C3C=CN21 DBVVQINTNHWWGH-UHFFFAOYSA-N 0.000 description 1
CMLQXZNMSSZRCH-UHFFFAOYSA-N indoloquinolizine Natural products C1=CC=CC2=C3N=C(C=CC=C4)C4=C3C=CN21 CMLQXZNMSSZRCH-UHFFFAOYSA-N 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000007040 multi-step synthesis reaction Methods 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
230000007935 neutral effect Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
FCGGDEKTUUSBPS-UHFFFAOYSA-M quinolizin-5-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.C1=CC=CC2=CC=CC=[N+]21 FCGGDEKTUUSBPS-UHFFFAOYSA-M 0.000 description 1
WYJAPUKIYAZSEM-UHFFFAOYSA-N rac-Eburnamonin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(=O)N5C2=C1 WYJAPUKIYAZSEM-UHFFFAOYSA-N 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
229960002922 vinburnine Drugs 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Landscapes

Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000580550A 1981-06-12 1988-10-18 Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a|- quinolizine Expired CA1261336A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000580550A CA1261336A (fr)	1981-06-12	1988-10-18	Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a\|- quinolizine

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
HU811753A HU186891B (en)	1981-06-12	1981-06-12	Process for producing esters of apovincaminic acid
HU1753/81		1981-06-12
CA000405030A CA1258071A (fr)	1981-06-12	1983-06-11	Procede de preparation d'esters de l'acide apovincaminique
CA000580550A CA1261336A (fr)	1981-06-12	1988-10-18	Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a\|- quinolizine

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000405030A Division CA1258071A (fr)	1981-06-12	1983-06-11	Procede de preparation d'esters de l'acide apovincaminique

Publications (1)

Publication Number	Publication Date
CA1261336A true CA1261336A (fr)	1989-09-26

Family

ID=25669729

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000580550A Expired CA1261336A (fr)	1981-06-12	1988-10-18	Obtention d'un racemique ou d'un derive optiquement actif d'hydroxyimino-octahydro-indolo¬2,3-a\|- quinolizine

Country Status (1)

Country	Link
CA (1)	CA1261336A (fr)

1988
- 1988-10-18 CA CA000580550A patent/CA1261336A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2006-09-26	MKEX	Expiry

Publication	Publication Date	Title
CH646969A5 (fr)	1984-12-28	Derives du beta-amino-3 nor-tropane.
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