NO744456L - - Google Patents

Info

Publication number: NO744456L
Authority: NO; Norway
Prior art keywords: formula; compounds; methoxy; ethyl; mixture
Prior art date: 1973-12-18

Application number

NO744456A

Other languages

English (en)

Norwegian (no)

Inventor

P Pfaeffli

Original Assignee

Sandoz Ag

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.)

1973-12-18

Filing date

1974-12-10

Publication date

1975-07-14

1973-12-18 Priority claimed from CH1768973A external-priority patent/CH588488A5/de

1974-02-06 Priority claimed from CH162174A external-priority patent/CH596207A5/de

1974-02-08 Priority claimed from CH176574A external-priority patent/CH593283A5/de

1974-12-10 Application filed by Sandoz Ag filed Critical Sandoz Ag

1975-07-14 Publication of NO744456L publication Critical patent/NO744456L/no

Links

239000000203 mixture Substances 0.000 claims description 39
150000001875 compounds Chemical class 0.000 claims description 37
229960002726 vincamine Drugs 0.000 claims description 27
239000002253 acid Substances 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 17
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
229910052794 bromium Inorganic materials 0.000 claims description 14
229910052731 fluorine Inorganic materials 0.000 claims description 14
239000011737 fluorine Substances 0.000 claims description 14
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
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 claims description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
239000000460 chlorine Substances 0.000 claims description 11
229910052801 chlorine Inorganic materials 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
238000000034 method Methods 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
238000003776 cleavage reaction Methods 0.000 claims description 6
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 claims description 6
230000007017 scission Effects 0.000 claims description 6
229910000039 hydrogen halide Inorganic materials 0.000 claims description 5
239000012433 hydrogen halide Substances 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
239000007795 chemical reaction product Substances 0.000 claims description 4
230000003287 optical effect Effects 0.000 claims description 4
150000002391 heterocyclic compounds Chemical class 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
229910001868 water Inorganic materials 0.000 description 29
238000003756 stirring Methods 0.000 description 25
229950006936 apovincamine Drugs 0.000 description 24
239000012071 phase Substances 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 20
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 19
238000002844 melting Methods 0.000 description 18
230000008018 melting Effects 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
238000000354 decomposition reaction Methods 0.000 description 10
229910052938 sodium sulfate Inorganic materials 0.000 description 10
235000011152 sodium sulphate Nutrition 0.000 description 10
239000002904 solvent Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
229910021529 ammonia Inorganic materials 0.000 description 8
238000002425 crystallisation Methods 0.000 description 8
230000008025 crystallization Effects 0.000 description 8
150000004702 methyl esters Chemical class 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 7
239000013078 crystal Substances 0.000 description 7
239000006260 foam Substances 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
229910000042 hydrogen bromide Inorganic materials 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000007787 solid Substances 0.000 description 6
239000002585 base Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
238000001228 spectrum Methods 0.000 description 5
238000005406 washing Methods 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
-1 alkali metal amide Chemical class 0.000 description 4
229950002641 brovincamine Drugs 0.000 description 4
239000006227 byproduct Substances 0.000 description 4
239000001569 carbon dioxide Substances 0.000 description 4
229910002092 carbon dioxide Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
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 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 3
229910001488 sodium perchlorate Inorganic materials 0.000 description 3
239000007858 starting material Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
238000009835 boiling Methods 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000006378 damage Effects 0.000 description 2
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
229910000043 hydrogen iodide Inorganic materials 0.000 description 2
150000007975 iminium salts Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
239000000155 melt Substances 0.000 description 2
150000002902 organometallic compounds Chemical class 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 2
229920000137 polyphosphoric acid Polymers 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
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 2
239000002994 raw material Substances 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000012546 transfer Methods 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
MFWFPCPYBKTJDV-JOCHJYFZSA-N (3s)-3-(diethoxymethyl)-3-ethyl-1-[2-(5-fluoro-1h-indol-3-yl)ethyl]piperidin-2-one Chemical compound O=C1[C@@](C(OCC)OCC)(CC)CCCN1CCC1=CNC2=CC=C(F)C=C12 MFWFPCPYBKTJDV-JOCHJYFZSA-N 0.000 description 1
NVRQFIVFOGYXSC-SFHVURJKSA-N (3s)-3-ethyl-1-[2-(5-fluoro-1h-indol-3-yl)ethyl]-2-oxopiperidine-3-carbaldehyde Chemical compound O=C1[C@](CC)(C=O)CCCN1CCC1=CNC2=CC=C(F)C=C12 NVRQFIVFOGYXSC-SFHVURJKSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
ZKIORVIXEWIOGB-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)ethanamine Chemical compound C1=C(F)C=C2C(CCN)=CNC2=C1 ZKIORVIXEWIOGB-UHFFFAOYSA-N 0.000 description 1
229940097276 5-methoxytryptamine Drugs 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
229910021576 Iron(III) bromide Inorganic materials 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010062519 Poor quality sleep Diseases 0.000 description 1
241000700159 Rattus Species 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
230000037396 body weight Effects 0.000 description 1
SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Chemical class [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000003925 fat Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000010438 heat treatment Methods 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
238000005984 hydrogenation reaction Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 1
230000007794 irritation Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
KYMUNKMWGDJFHK-UHFFFAOYSA-N methyl 2-(dimethoxyphosphorylmethoxy)acetate Chemical compound COC(=O)COCP(=O)(OC)OC KYMUNKMWGDJFHK-UHFFFAOYSA-N 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000012552 review Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000000126 substance Substances 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
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
208000009999 tuberous sclerosis Diseases 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
General Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Psychiatry (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hospice & Palliative Care (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO744456A 1973-12-18 1974-12-10 NO744456L (da)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CH1768973A CH588488A5 (en)	1973-12-18	1973-12-18	Vincamine derivs for treating behaviour disorders - by ring closure of indoloquinolizine deriv
CH162174A CH596207A5 (en)	1974-02-06	1974-02-06	Vincamine derivs for treating behaviour disorders
CH176574A CH593283A5 (en)	1974-02-08	1974-02-08	Vincamine derivs for treating behaviour disorders - by ring closure of indoloquinolizine deriv

Publications (1)

Publication Number	Publication Date
NO744456L true NO744456L (da)	1975-07-14

Family

ID=27173122

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO744456A NO744456L (da)	1973-12-18	1974-12-10

Country Status (16)

Country	Link
JP (1)	JPS5817474B2 (da)
CA (1)	CA1051899A (da)
DD (1)	DD116043A5 (da)
DE (1)	DE2458164A1 (da)
DK (1)	DK139358B (da)
ES (3)	ES432952A1 (da)
FI (1)	FI59096C (da)
FR (1)	FR2254342B1 (da)
GB (1)	GB1492579A (da)
HK (1)	HK53980A (da)
IE (1)	IE40791B1 (da)
MY (1)	MY8100186A (da)
NL (1)	NL7416237A (da)
NO (1)	NO744456L (da)
PH (1)	PH12927A (da)
SE (1)	SE422798B (da)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2396759A1 (fr) *	1977-07-06	1979-02-02	Omnium Chimique Sa	Nouveaux composes heterocycliques, derives de la vincamine, leur preparation et leur application comme medicaments, notamment dans le domaine des insuffisances cardio-circulatoires, cerebro-vasculaires ou respiratoires
HU177498B (en) *	1977-07-27	1981-10-28	Richter Gedeon Vegyeszet	Process for preparing new vincinic acid and apovincinic acid esters
FR2423493A1 (fr) *	1977-10-19	1979-11-16	Omnium Chimique Sa	Nouveaux composes heterocycliques derives de l'apo-vincamine, leur preparation et leur application comme medicaments, notamment dans le domaine des insuffisances cardio-circulatoires, cerebro-vasculaires et respiratoires
FR2407931A1 (fr) *	1977-11-02	1979-06-01	Synthelabo	Derives de l'eburnamenine et leur application en therapeutique
JPS5493000A (en) *	1977-12-28	1979-07-23	Sandoz Ag	Improvement of organic compound
DE2800063A1 (de) *	1978-01-02	1979-07-12	Sandoz Ag	10-bromvincamin, seine herstellung und verwendung
US4315011A (en) *	1978-07-12	1982-02-09	Richter Gedeon Vegyeszeti Gyar Rt.	1-Alkyl-9-bromohexahydroindolo quinolizium salts and use thereof to increase blood flow
FR2445328A1 (fr) *	1978-07-12	1980-07-25	Richter Gedeon Vegyeszet	Derives du 14-oxo-e-homo-eburnane, leur procede de preparation et leur utilisation comme medicament
US4285949A (en) *	1978-12-11	1981-08-25	Omnichem Societe Anonyme	Vincamine derivatives, their preparation and therapeutical use
HU177732B (en) *	1978-12-15	1981-12-28	Richter Gedeon Vegyeszet	Process for producing 10-bromo-vincamine and acid additional salts thereof,and 10-bromo-14-epivincamine
HU180928B (en) *	1979-08-06	1983-05-30	Richter Gedeon Vegyeszet	Process for preparing new brominated 15-hydroxy-e-homo-eburane derivatives
HU180929B (en) *	1979-08-13	1983-05-30	Richter Gedeon Vegyeszet	Process for producing new bromo-vincamone derivatives
HU185305B (en) *	1981-08-23	1985-01-28	Richter Gedeon Vegyeszet	Process for preparing vincine and apovincine
HU183326B (en) *	1981-02-11	1984-04-28	Richter Gedeon Vegyeszet	Process for preparing new apovincaminol-3',4',5'-trimethoxy-benzoates substituted in the a ring and acid addition salts thereof
ES8604952A1 (es) *	1985-11-05	1986-03-16	Covex Sa	Procedimiento para la preparacion de los compuestos 10-11 bromo-14,15-dihidro-14 b-hidroxi-(3x,16x)-eburnamenina-14- carboxilato de metilo
US4883876A (en) *	1987-09-07	1989-11-28	Taisho Pharmaceutical Co., Ltd.	Acylated vincaminic acid derivatives

1974
- 1974-12-09 DK DK639774AA patent/DK139358B/da not_active IP Right Cessation
- 1974-12-09 DE DE19742458164 patent/DE2458164A1/de active Granted
- 1974-12-09 SE SE7415416A patent/SE422798B/xx not_active IP Right Cessation
- 1974-12-10 NO NO744456A patent/NO744456L/no unknown
- 1974-12-10 FI FI3552/74A patent/FI59096C/fi active
- 1974-12-13 NL NL7416237A patent/NL7416237A/xx not_active Application Discontinuation
- 1974-12-16 GB GB54159/74A patent/GB1492579A/en not_active Expired
- 1974-12-16 PH PH16634A patent/PH12927A/en unknown
- 1974-12-16 IE IE2591/74A patent/IE40791B1/xx unknown
- 1974-12-16 ES ES432952A patent/ES432952A1/es not_active Expired
- 1974-12-17 CA CA216,230A patent/CA1051899A/en not_active Expired
- 1974-12-17 JP JP49144170A patent/JPS5817474B2/ja not_active Expired
- 1974-12-17 DD DD183107A patent/DD116043A5/xx unknown
- 1974-12-18 FR FR7441717A patent/FR2254342B1/fr not_active Expired
1976
- 1976-08-16 ES ES450741A patent/ES450741A1/es not_active Expired
- 1976-08-16 ES ES450740A patent/ES450740A1/es not_active Expired
1980
- 1980-09-25 HK HK539/80A patent/HK53980A/xx unknown
1981
- 1981-12-30 MY MY186/81A patent/MY8100186A/xx unknown

Also Published As

Publication number	Publication date
IE40791L (en)	1975-06-18
ES450740A1 (es)	1977-12-16
FR2254342A1 (da)	1975-07-11
DK139358B (da)	1979-02-05
DE2458164C2 (da)	1991-04-18
ES450741A1 (es)	1978-03-16
IE40791B1 (en)	1979-08-15
ES432952A1 (es)	1977-02-16
SE7415416L (da)	1975-06-19
HK53980A (en)	1980-10-03
MY8100186A (en)	1981-12-31
DK139358C (da)	1979-07-09
GB1492579A (en)	1977-11-23
DD116043A5 (da)	1975-11-05
DE2458164A1 (de)	1975-06-26
NL7416237A (nl)	1975-06-20
AU7648374A (en)	1976-06-17
JPS50105700A (da)	1975-08-20
DK639774A (da)	1975-08-25
FI59096B (fi)	1981-02-27
JPS5817474B2 (ja)	1983-04-07
SE422798B (sv)	1982-03-29
FI355274A (da)	1975-06-19
FI59096C (fi)	1981-06-10
PH12927A (en)	1979-10-10
CA1051899A (en)	1979-04-03
FR2254342B1 (da)	1978-07-21

Publication	Publication Date	Title
NO744456L (da)	1975-07-14
JP2716146B2 (ja)	1998-02-18	縮合インドール誘導体およびその製造方法
Grunwell et al.	1991	The formal oxidative addition of electron-rich transoid dienes to bromonaphthoquinones
DK2504334T3 (da)	2014-12-08	Fremgangsmåde til oprensning af methyl-{4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamat
EP0204349A2 (de)	1986-12-10	Neue heteroaromatische Aminderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
IE902657A1 (en)	1991-02-27	New substituted 1H-indazole-3-carboxamides
EP1546099B1 (en)	2008-12-31	3,6-disubstituted azabicyclo 3.1.0 hexane derivatives useful as muscarinic receptor antagonists
NO175259B (no)	1994-06-13	Analogifremgangsmåte for fremstilling av terapeutisk aktive triazolo-1,4-diazepinforbindelser
KR930011038B1 (ko)	1993-11-20	테트라하이드로 벤즈이미다졸 유도체 및 이의 제조방법
AU597996B2 (en)	1990-06-14	New 1H,3H-pyrrolo{1,2-c}thiazole derivatives, preparation thereof and pharmaceutical compositions containing them
US20090082358A1 (en)	2009-03-26	Vanilloid receptor ligands and their use in treatments
EP2794607B1 (en)	2017-05-10	Derivatives of aza adamantane and uses thereof
EP3770148A1 (en)	2021-01-27	Receptor inhibitor, pharmaceutical composition comprising same, and use thereof
FR2631625A1 (fr)	1989-11-24	Derives de phenyl-6 piperazinylalkyl-3 1h,3h-pyrimidinedione-2,4, leur preparation et leur application en therapeutique
JP3040182B2 (ja)	2000-05-08	イミダゾピリダジン誘導体、その用途及び製造法
CA2096138A1 (en)	1993-03-14	.beta.-carboline derivatives their production and use in pharmaceutical agents
CH630629A5 (fr)	1982-06-30	Derives de la morphine, leur procede de preparation et leur application comme medicament.
JPS62111983A (ja)	1987-05-22	１２−および１３−臭素−エルゴリン誘導体、その製法およびこれを含有する抑うつ性疾患症候群の精神障害の治療剤
LU86743A1 (fr)	1987-09-03	Nouvelles 8a-acylamino-ergolines,leur preparation et leur utilisation comme medicaments
US3086972A (en)	1963-04-23	Aza-thiaxanthene derivatives
Wren et al.	1916	XLVI.—Studies in the phenylsuccinic acid series. Part III. The optically active phenylsuccinic acids and their derivatives
EP0402232A1 (fr)	1990-12-12	Dérivés de pyridobenzoindole, leur préparation et les compositions qui les contiennent
US3882119A (en)	1975-05-06	Tetracyclic substituted phthalazine compounds
JPS61137885A (ja)	1986-06-25	１，８−ナフチリジン誘導体、そのエステルおよびその塩
US4851420A (en)	1989-07-25	2,6-diamino-3-halobenzylpyridines and processes for their manufacture as well as their use in pharmaceuticals