CS255876B2 - Process for preparing new 10 alpha-methoxy-6-methyl-ergolines - Google Patents
Process for preparing new 10 alpha-methoxy-6-methyl-ergolines Download PDFInfo
- Publication number
- CS255876B2 CS255876B2 CS864585A CS458586A CS255876B2 CS 255876 B2 CS255876 B2 CS 255876B2 CS 864585 A CS864585 A CS 864585A CS 458586 A CS458586 A CS 458586A CS 255876 B2 CS255876 B2 CS 255876B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methyl
- formula
- hydrogen
- lumilysergol
- halo
- Prior art date
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- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 10
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 10
- 239000000460 chlorine Chemical group 0.000 claims abstract description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052740 iodine Chemical group 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- -1 5-bromo-nicotinoyl group Chemical group 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
- 150000002148 esters Chemical class 0.000 claims description 9
- 230000032050 esterification Effects 0.000 claims description 8
- 238000005886 esterification reaction Methods 0.000 claims description 8
- 238000006552 photochemical reaction Methods 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- QCCLDOMKAQLVCM-IIWDCPNDSA-N (6aR,10aR)-9-methoxy-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline Chemical class COC1CN([C@@H]2CC3=CNC4=CC=CC([C@H]2C1)=C34)C QCCLDOMKAQLVCM-IIWDCPNDSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- YSEXMKHXIOCEJA-FVFQAYNVSA-N Nicergoline Chemical compound C([C@@H]1C[C@]2([C@H](N(C)C1)CC=1C3=C2C=CC=C3N(C)C=1)OC)OC(=O)C1=CN=CC(Br)=C1 YSEXMKHXIOCEJA-FVFQAYNVSA-N 0.000 abstract description 11
- 229960003642 nicergoline Drugs 0.000 abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000903 blocking effect Effects 0.000 abstract description 3
- 239000011630 iodine Chemical group 0.000 abstract description 3
- 238000006198 methoxylation reaction Methods 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 2
- 239000000810 peripheral vasodilating agent Substances 0.000 abstract description 2
- 229960002116 peripheral vasodilator Drugs 0.000 abstract description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- 101150049660 DRD2 gene Proteins 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 238000012986 modification Methods 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- BIXJFIJYBLJTMK-UHFFFAOYSA-N Lysergol Natural products C1=CC(C2=CC(CO)CN(C2C2)C)=C3C2=CNC3=C1 BIXJFIJYBLJTMK-UHFFFAOYSA-N 0.000 description 7
- 239000000010 aprotic solvent Substances 0.000 description 7
- BIXJFIJYBLJTMK-MEBBXXQBSA-N lysergol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=CNC3=C1 BIXJFIJYBLJTMK-MEBBXXQBSA-N 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000007069 methylation reaction Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- FQIUCPGDKPXSLL-UHFFFAOYSA-N 5-bromopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(Br)=C1 FQIUCPGDKPXSLL-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical group O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
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- 239000002244 precipitate Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
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- ZOUBAHRISDTOBN-YMTOWFKASA-N [(6ar,9r)-5-bromo-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]methanol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=C(Br)NC3=C1 ZOUBAHRISDTOBN-YMTOWFKASA-N 0.000 description 3
- UDIJSKHBACNYIE-YMTOWFKASA-N [(6ar,9r)-5-chloro-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]methanol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=C(Cl)NC3=C1 UDIJSKHBACNYIE-YMTOWFKASA-N 0.000 description 3
- MOYIIEKIOZCSQI-YMTOWFKASA-N [(6ar,9r)-5-chloro-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]methyl dihydrogen phosphate Chemical compound C1=CC(C2=C[C@@H](COP(O)(O)=O)CN([C@@H]2C2)C)=C3C2=C(Cl)NC3=C1 MOYIIEKIOZCSQI-YMTOWFKASA-N 0.000 description 3
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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- 230000011987 methylation Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ZAGRKAFMISFKIO-UHFFFAOYSA-N Isolysergic acid Natural products C1=CC(C2=CC(CN(C2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
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- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
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- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 239000000126 substance Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 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
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU852446A HU193781B (en) | 1985-06-21 | 1985-06-21 | Process for producing 10alpha-methoxy-6-methylergoline derivatives and acid additional salts thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS255876B2 true CS255876B2 (en) | 1988-03-15 |
Family
ID=10959396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS864585A CS255876B2 (en) | 1985-06-21 | 1986-06-20 | Process for preparing new 10 alpha-methoxy-6-methyl-ergolines |
Country Status (14)
| Country | Link |
|---|---|
| BE (1) | BE904956A (hu) |
| CS (1) | CS255876B2 (hu) |
| DD (1) | DD246110A5 (hu) |
| DE (1) | DE3620487A1 (hu) |
| DK (1) | DK291986A (hu) |
| ES (1) | ES8801263A1 (hu) |
| FR (1) | FR2583755B1 (hu) |
| GB (1) | GB2177090B (hu) |
| GR (1) | GR861619B (hu) |
| HU (1) | HU193781B (hu) |
| IT (1) | IT1190135B (hu) |
| LU (1) | LU86486A1 (hu) |
| NL (1) | NL8601584A (hu) |
| PT (1) | PT82807B (hu) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU196598B (en) * | 1986-04-25 | 1988-12-28 | Richter Gedeon Vegyeszet | Process for producing 1- and/or 8-substituted 2-halogenated ergoline derivatives and pharmaceutics comprising such compounds |
| GB9603226D0 (en) * | 1996-02-15 | 1996-04-17 | Pharmacia Spa | Heterocyclyl-ergoline derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1094965B (it) * | 1978-04-05 | 1985-08-10 | Corvi Mora E | Procedimento di preparazione di derivati del lisergolo |
| HU193782B (en) * | 1985-06-21 | 1987-11-30 | Richter Gedeon Vegyeszet | Process for producing 2-halogeno-nicergoline derivatives and acid additional salts thereof |
-
1985
- 1985-06-21 HU HU852446A patent/HU193781B/hu not_active IP Right Cessation
-
1986
- 1986-06-19 FR FR868608869A patent/FR2583755B1/fr not_active Expired - Lifetime
- 1986-06-19 DE DE19863620487 patent/DE3620487A1/de not_active Withdrawn
- 1986-06-19 BE BE0/216805A patent/BE904956A/fr not_active IP Right Cessation
- 1986-06-19 IT IT20854/86A patent/IT1190135B/it active
- 1986-06-19 NL NL8601584A patent/NL8601584A/nl not_active Application Discontinuation
- 1986-06-20 LU LU86486A patent/LU86486A1/de unknown
- 1986-06-20 ES ES556358A patent/ES8801263A1/es not_active Expired
- 1986-06-20 GR GR861619A patent/GR861619B/el unknown
- 1986-06-20 DK DK291986A patent/DK291986A/da not_active Application Discontinuation
- 1986-06-20 PT PT82807A patent/PT82807B/pt not_active IP Right Cessation
- 1986-06-20 DD DD86291508A patent/DD246110A5/de not_active IP Right Cessation
- 1986-06-20 GB GB8615121A patent/GB2177090B/en not_active Expired
- 1986-06-20 CS CS864585A patent/CS255876B2/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES8801263A1 (es) | 1988-01-01 |
| GB2177090A (en) | 1987-01-14 |
| DK291986A (da) | 1986-12-22 |
| IT8620854A0 (it) | 1986-06-19 |
| DD246110A5 (de) | 1987-05-27 |
| PT82807B (pt) | 1988-04-21 |
| GB2177090B (en) | 1989-07-12 |
| FR2583755B1 (fr) | 1990-06-22 |
| BE904956A (fr) | 1986-12-19 |
| FR2583755A1 (fr) | 1986-12-26 |
| DE3620487A1 (de) | 1987-01-02 |
| NL8601584A (nl) | 1987-01-16 |
| GB8615121D0 (en) | 1986-07-23 |
| ES556358A0 (es) | 1988-01-01 |
| IT1190135B (it) | 1988-02-10 |
| HUT41023A (en) | 1987-03-30 |
| HU193781B (en) | 1987-11-30 |
| LU86486A1 (de) | 1986-12-02 |
| GR861619B (en) | 1986-10-21 |
| DK291986D0 (da) | 1986-06-20 |
| PT82807A (en) | 1986-07-01 |
| IT8620854A1 (it) | 1987-12-19 |
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