DE2625116C2 - Verfahren zur Herstellung von 4-Hydroxy-aporphin-Derivaten - Google Patents
Verfahren zur Herstellung von 4-Hydroxy-aporphin-DerivatenInfo
- Publication number
- DE2625116C2 DE2625116C2 DE2625116A DE2625116A DE2625116C2 DE 2625116 C2 DE2625116 C2 DE 2625116C2 DE 2625116 A DE2625116 A DE 2625116A DE 2625116 A DE2625116 A DE 2625116A DE 2625116 C2 DE2625116 C2 DE 2625116C2
- Authority
- DE
- Germany
- Prior art keywords
- trifluoroacetic acid
- acid
- chj
- hydroxy
- vanadyl
- Prior art date
- 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
Links
- 238000000034 method Methods 0.000 title claims description 14
- SIMIGYXMQWAMGC-UHFFFAOYSA-N 6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-4-ol Chemical class C12=CC=CC=C2CC2N(C)CC(O)C3=CC=CC1=C32 SIMIGYXMQWAMGC-UHFFFAOYSA-N 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- -1 vanadyl fluoride Chemical compound 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- HHQFLEDKAVLHOM-UHFFFAOYSA-N oxovanadium;trihydrofluoride Chemical compound F.F.F.[V]=O HHQFLEDKAVLHOM-UHFFFAOYSA-N 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- XFQYJNINHLZMIU-UHFFFAOYSA-N cataline Natural products CN1CC(O)C2=CC(OC)=C(OC)C3=C2C1CC1=C3C=C(OC)C(OC)=C1 XFQYJNINHLZMIU-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000005287 vanadyl group Chemical group 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KGPAYJZAMGEDIQ-KRWDZBQOSA-N Laudanosine Chemical compound C1=C(OC)C(OC)=CC=C1C[C@H]1C2=CC(OC)=C(OC)C=C2CCN1C KGPAYJZAMGEDIQ-KRWDZBQOSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- BZKUYNBAFQJRDM-UHFFFAOYSA-N aporphine Chemical compound C12=CC=CC=C2CC2N(C)CCC3=CC=CC1=C32 BZKUYNBAFQJRDM-UHFFFAOYSA-N 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
- 239000013078 crystal Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- KGPAYJZAMGEDIQ-UHFFFAOYSA-N laudanosine Natural products C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCN1C KGPAYJZAMGEDIQ-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- ZYXKNPNUJNUFET-UHFFFAOYSA-N 1,2,9,10-tetraethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-4-ol Chemical compound CN1CC(O)C2=CC(OCC)=C(OCC)C3=C2C1CC1=C3C=C(OCC)C(OCC)=C1 ZYXKNPNUJNUFET-UHFFFAOYSA-N 0.000 description 2
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 2
- MVRYYBFJTYHDQY-UHFFFAOYSA-N 6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-1-ol Chemical class C12=CC=CC=C2CC2N(C)CCC3=CC=C(O)C1=C32 MVRYYBFJTYHDQY-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 2
- MAWRLMCDVKBYJB-UHFFFAOYSA-N (+-)-normecambroline Natural products C12=C3C4=CC(O)=CC=C4CC2NCCC1=CC1=C3OCO1 MAWRLMCDVKBYJB-UHFFFAOYSA-N 0.000 description 1
- 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
- RUZIUYOSRDWYQF-HNNXBMFYSA-N (S)-glaucine Chemical compound CN1CCC2=CC(OC)=C(OC)C3=C2[C@@H]1CC1=C3C=C(OC)C(OC)=C1 RUZIUYOSRDWYQF-HNNXBMFYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZIVNVIZPOKSNGZ-UHFFFAOYSA-N 1,2,9,10-tetramethoxy-6-propyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-4-ol Chemical compound C12=CC(OC)=C(OC)C=C2CC2N(CCC)CC(O)C3=CC(OC)=C(OC)C1=C32 ZIVNVIZPOKSNGZ-UHFFFAOYSA-N 0.000 description 1
- HXVWWPSVYMTSQW-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-propyl-3,4-dihydro-1h-isoquinoline Chemical compound CCCN1CCC2=CC(OC)=C(OC)C=C2C1CC1=CC=C(OC)C(OC)=C1 HXVWWPSVYMTSQW-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 125000006185 3,4-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920000818 Catalin Polymers 0.000 description 1
- ZTXGGRMVULLHNF-UHFFFAOYSA-N Dehydroneolitsine Natural products CN1CCc2cc3OCOc3c4c5cc6OCOc6cc5cc1c24 ZTXGGRMVULLHNF-UHFFFAOYSA-N 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
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 240000005086 Glaucium flavum Species 0.000 description 1
- 235000000629 Glaucium flavum Nutrition 0.000 description 1
- DABPOQZSGVNAAS-UHFFFAOYSA-N Glaucocalactone Natural products O=CC12C3C(C4)OC(=O)C2C(C)(C)CCC1OC(=O)C13CC4C(=C)C1OC(=O)C DABPOQZSGVNAAS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- OKPNYGAWTYOBFZ-UHFFFAOYSA-N Pirenoxine Chemical compound C12=NC3=CC=CC=C3OC2=CC(=O)C2=C1C(=O)C=C(C(=O)O)N2 OKPNYGAWTYOBFZ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- QCMQEZNBBPGFKQ-UHFFFAOYSA-N Thalisopynine Natural products CN1CCC2=C(OC)C(OC)=C(OC)C3=C2C1CC1=C3C=C(OC)C(O)=C1 QCMQEZNBBPGFKQ-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 150000008441 aporphines Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 125000001743 benzylic group Chemical group 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
- 239000006227 byproduct Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229930004041 glaucine Natural products 0.000 description 1
- 229940113086 glaucine Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- FVRABHGHBLRNNR-UHFFFAOYSA-N liriodenine Natural products O=C1C=CC=c2c1cc3nccc4cc5OCOc5c2c34 FVRABHGHBLRNNR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-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
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 230000017105 transposition Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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)
- Health & Medical Sciences (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2625116A DE2625116C2 (de) | 1976-06-04 | 1976-06-04 | Verfahren zur Herstellung von 4-Hydroxy-aporphin-Derivaten |
| US05/800,492 US4120964A (en) | 1976-06-04 | 1977-05-25 | Aporphine derivatives |
| IE1110/77A IE44937B1 (en) | 1976-06-04 | 1977-05-30 | 4-hydroxy-aporphine derivatives |
| GB23115/77A GB1521020A (en) | 1976-06-04 | 1977-06-01 | 4-hydrox-aporphine derivatives |
| SE7706488A SE433212B (sv) | 1976-06-04 | 1977-06-03 | Forfarande for framstellning av 4-hydroxi-aporfin-derivat |
| NL7706180A NL7706180A (nl) | 1976-06-04 | 1977-06-03 | Werkwijze voor de bereiding van nieuwe aporfine- verbindingen. |
| BE6046041A BE855412A (fr) | 1976-06-04 | 1977-06-03 | Derives nouveaux de 4-hydroxy-aporphine et leur mode de preparation |
| AU25809/77A AU508171B2 (en) | 1976-06-04 | 1977-06-03 | 4 hydroxy-aporphine derivatives |
| CH691177A CH629782A5 (de) | 1976-06-04 | 1977-06-03 | Verfahren zur herstellung von 4-hydroxy-aporphinderivaten. |
| FR7716976A FR2353534A1 (fr) | 1976-06-04 | 1977-06-03 | Derives nouveaux de 4-hydroxy-aporphine, leur mode preparation et leur application pharmacologique |
| LU77482A LU77482A1 (enExample) | 1976-06-04 | 1977-06-03 | |
| JP6561677A JPS535169A (en) | 1976-06-04 | 1977-06-03 | Production of novel 44 hydroxyyapolphine derivatiles |
| DK248277A DK248277A (da) | 1976-06-04 | 1977-06-03 | 4-hydroxy-aporphinderivater samt deres fremstilling og anvendelse |
| ES459504A ES459504A1 (es) | 1976-06-04 | 1977-06-04 | Procedimiento para la preparacion de derivados de la 4-hi- droxi-aporfina. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2625116A DE2625116C2 (de) | 1976-06-04 | 1976-06-04 | Verfahren zur Herstellung von 4-Hydroxy-aporphin-Derivaten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2625116A1 DE2625116A1 (de) | 1977-12-22 |
| DE2625116C2 true DE2625116C2 (de) | 1984-01-26 |
Family
ID=5979808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2625116A Expired DE2625116C2 (de) | 1976-06-04 | 1976-06-04 | Verfahren zur Herstellung von 4-Hydroxy-aporphin-Derivaten |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4120964A (enExample) |
| JP (1) | JPS535169A (enExample) |
| AU (1) | AU508171B2 (enExample) |
| BE (1) | BE855412A (enExample) |
| CH (1) | CH629782A5 (enExample) |
| DE (1) | DE2625116C2 (enExample) |
| DK (1) | DK248277A (enExample) |
| ES (1) | ES459504A1 (enExample) |
| FR (1) | FR2353534A1 (enExample) |
| GB (1) | GB1521020A (enExample) |
| IE (1) | IE44937B1 (enExample) |
| LU (1) | LU77482A1 (enExample) |
| NL (1) | NL7706180A (enExample) |
| SE (1) | SE433212B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2757335C3 (de) * | 1977-12-22 | 1982-03-25 | Gödecke AG, 1000 Berlin | Verfahren zur O-Methylierung von Hydroxyaporphinen |
| DE2757281C3 (de) * | 1977-12-22 | 1980-10-23 | Goedecke Ag, 1000 Berlin | Verfahren zur Herstellung von 1 -Hydroxy-Aporphinderivaten |
| FI68813C (fi) * | 1978-08-21 | 1985-11-11 | Dow Chemical Co | Foerfarande foer framstaellning av terapeutiskt effektiva 1- och d,1-glausinfosfatsalter |
| DE3324089A1 (de) * | 1983-07-05 | 1985-01-17 | Basf Ag, 6700 Ludwigshafen | Elektrophotographische aufzeichnungsmaterialien mit verbesserter photoempfindlichkeit |
| DE3324090A1 (de) * | 1983-07-05 | 1985-01-17 | Basf Ag, 6700 Ludwigshafen | Elektrophotographische aufzeichnungsmaterialien mit verbesserter photoempfindlichkeit |
| US5156847A (en) * | 1990-09-20 | 1992-10-20 | Walter H. Lewis | Wound-healing composition |
| US5474782A (en) * | 1994-05-20 | 1995-12-12 | Woundfast Pharmaceuticals, Inc. | Wound-healing composition and method |
| US5659037A (en) * | 1994-08-18 | 1997-08-19 | Abbott Laboratories | Process for preparing chiral tetracyclic dopaminergic compounds |
| DE19535762A1 (de) * | 1995-09-26 | 1997-03-27 | Basf Ag | Verfahren zur Racematspaltung |
| US5932617A (en) * | 1998-02-06 | 1999-08-03 | Woundfast Pharmaceuticals Inc. | Wound-treating composition and method |
| US6210680B1 (en) | 1999-06-11 | 2001-04-03 | Univera Pharmaceuticals, Inc. | Method for the prevention and treatment of chronic venous insufficiency |
| US20030187011A1 (en) * | 2001-12-20 | 2003-10-02 | Lashuel Hilal A. | Apomorphine inhibitors of amyloid-beta (Abeta) fibril formation and their use in amyloidosis based disease |
| TWI404536B (zh) * | 2008-06-20 | 2013-08-11 | Standard Chem & Pharm Co Ltd | 阿朴芬化合物及其醫藥用途 |
| CN105315208A (zh) * | 2014-07-17 | 2016-02-10 | 中国科学院兰州化学物理研究所 | 阿朴菲类生物碱及其制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3131191A (en) * | 1962-08-08 | 1964-04-28 | Smith Kline French Lab | Process for the preparation of noraporphines |
-
1976
- 1976-06-04 DE DE2625116A patent/DE2625116C2/de not_active Expired
-
1977
- 1977-05-25 US US05/800,492 patent/US4120964A/en not_active Expired - Lifetime
- 1977-05-30 IE IE1110/77A patent/IE44937B1/en unknown
- 1977-06-01 GB GB23115/77A patent/GB1521020A/en not_active Expired
- 1977-06-03 BE BE6046041A patent/BE855412A/xx not_active IP Right Cessation
- 1977-06-03 FR FR7716976A patent/FR2353534A1/fr active Granted
- 1977-06-03 SE SE7706488A patent/SE433212B/xx unknown
- 1977-06-03 JP JP6561677A patent/JPS535169A/ja active Pending
- 1977-06-03 LU LU77482A patent/LU77482A1/xx unknown
- 1977-06-03 CH CH691177A patent/CH629782A5/de not_active IP Right Cessation
- 1977-06-03 AU AU25809/77A patent/AU508171B2/en not_active Expired
- 1977-06-03 DK DK248277A patent/DK248277A/da not_active Application Discontinuation
- 1977-06-03 NL NL7706180A patent/NL7706180A/xx not_active Application Discontinuation
- 1977-06-04 ES ES459504A patent/ES459504A1/es not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| NICHTS-ERMITTELT |
Also Published As
| Publication number | Publication date |
|---|---|
| DK248277A (da) | 1977-12-05 |
| IE44937L (en) | 1977-12-04 |
| JPS535169A (en) | 1978-01-18 |
| FR2353534B1 (enExample) | 1980-03-07 |
| BE855412A (fr) | 1977-12-05 |
| CH629782A5 (de) | 1982-05-14 |
| AU508171B2 (en) | 1980-03-13 |
| IE44937B1 (en) | 1982-05-19 |
| LU77482A1 (enExample) | 1977-09-22 |
| FR2353534A1 (fr) | 1977-12-30 |
| SE433212B (sv) | 1984-05-14 |
| ES459504A1 (es) | 1978-05-01 |
| GB1521020A (en) | 1978-08-09 |
| AU2580977A (en) | 1978-12-07 |
| DE2625116A1 (de) | 1977-12-22 |
| US4120964A (en) | 1978-10-17 |
| SE7706488L (sv) | 1977-12-05 |
| NL7706180A (nl) | 1977-12-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OC | Search report available | ||
| 8110 | Request for examination paragraph 44 | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |