DD278793A5 - Verfahren zur herstellung eines unsymmetrischen ester-derivates der 1,4-dihydropyridin-3,5-dicarbonsaeure - Google Patents
Verfahren zur herstellung eines unsymmetrischen ester-derivates der 1,4-dihydropyridin-3,5-dicarbonsaeure Download PDFInfo
- Publication number
- DD278793A5 DD278793A5 DD87325139A DD32513987A DD278793A5 DD 278793 A5 DD278793 A5 DD 278793A5 DD 87325139 A DD87325139 A DD 87325139A DD 32513987 A DD32513987 A DD 32513987A DD 278793 A5 DD278793 A5 DD 278793A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- preparation
- acid
- mixture
- general formula
- carbon atoms
- Prior art date
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- 238000004519 manufacturing process Methods 0.000 title claims description 26
- 239000002253 acid Substances 0.000 title claims description 5
- 150000002148 esters Chemical class 0.000 title abstract description 4
- -1 ester derivative of 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 22
- 238000010992 reflux Methods 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 150000002009 diols Chemical class 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 2
- 125000005879 dioxolanyl group Chemical group 0.000 claims 1
- 239000002798 polar solvent Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 56
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 7
- 150000003839 salts Chemical class 0.000 abstract description 6
- 230000003287 optical effect Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
- 239000000047 product Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- FZJCXIDLUFPGPP-UHFFFAOYSA-N propan-2-ol;toluene Chemical compound CC(C)O.CC1=CC=CC=C1 FZJCXIDLUFPGPP-UHFFFAOYSA-N 0.000 description 8
- 239000012429 reaction media Substances 0.000 description 8
- 239000006260 foam Substances 0.000 description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- TZDPJNSHSWMCPN-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 TZDPJNSHSWMCPN-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 229960001783 nicardipine Drugs 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000004873 systolic arterial blood pressure Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 3
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 3
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- PAWSVPVNIXFKOS-IHWYPQMZSA-N (Z)-2-aminobutenoic acid Chemical compound C\C=C(/N)C(O)=O PAWSVPVNIXFKOS-IHWYPQMZSA-N 0.000 description 2
- COLPLFZHPXIFCQ-UHFFFAOYSA-N 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class OC(=O)C1=CNC=C(C(O)=O)C1 COLPLFZHPXIFCQ-UHFFFAOYSA-N 0.000 description 2
- SUPUBCWGOUYLIG-UHFFFAOYSA-N 1-(4-chlorophenyl)piperidin-4-one Chemical compound C1=CC(Cl)=CC=C1N1CCC(=O)CC1 SUPUBCWGOUYLIG-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 1
- PAKCOSURAUIXFG-LURJTMIESA-N (2s)-3-prop-2-enoxypropane-1,2-diol Chemical compound OC[C@H](O)COCC=C PAKCOSURAUIXFG-LURJTMIESA-N 0.000 description 1
- DOKVFNMLKTUXTP-UHFFFAOYSA-N (8-phenyl-1,4-dioxa-8-azaspiro[4.5]decan-3-yl)methanol Chemical compound O1C(CO)COC11CCN(C=2C=CC=CC=2)CC1 DOKVFNMLKTUXTP-UHFFFAOYSA-N 0.000 description 1
- RHLPIVFFQDQVAN-UHFFFAOYSA-N (8-phenyl-1,4-dioxa-8-azaspiro[4.5]decan-3-yl)methyl 3-oxobutanoate Chemical compound O1C(COC(=O)CC(=O)C)COC11CCN(C=2C=CC=CC=2)CC1 RHLPIVFFQDQVAN-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- JUKBFIBHTNWOMG-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)piperidin-4-one Chemical compound ClC1=CC(Cl)=CC=C1N1CCC(=O)CC1 JUKBFIBHTNWOMG-UHFFFAOYSA-N 0.000 description 1
- NKDMZHXGTPQTRF-UHFFFAOYSA-N 1-(4-hydroxyphenyl)piperidin-4-one Chemical compound C1=CC(O)=CC=C1N1CCC(=O)CC1 NKDMZHXGTPQTRF-UHFFFAOYSA-N 0.000 description 1
- JWWPZSUQVZPAHD-UHFFFAOYSA-N 1-(4-methylphenyl)piperidin-4-one Chemical compound C1=CC(C)=CC=C1N1CCC(=O)CC1 JWWPZSUQVZPAHD-UHFFFAOYSA-N 0.000 description 1
- VPGLFNOKHAIGEC-UHFFFAOYSA-N 1-phenylpiperidin-4-one Chemical compound C1CC(=O)CCN1C1=CC=CC=C1 VPGLFNOKHAIGEC-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 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
- GCUMHOAQJSSYSV-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC(Cl)=C1Cl GCUMHOAQJSSYSV-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical class COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 229960001413 acetanilide Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 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
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- FNIATMYXUPOJRW-UHFFFAOYSA-N cyclohexylidene Chemical group [C]1CCCCC1 FNIATMYXUPOJRW-UHFFFAOYSA-N 0.000 description 1
- PWAPCRSSMCLZHG-UHFFFAOYSA-N cyclopentylidene Chemical group [C]1CCCC1 PWAPCRSSMCLZHG-UHFFFAOYSA-N 0.000 description 1
- MPFLRYZEEAQMLQ-UHFFFAOYSA-N dinicotinic acid Chemical compound OC(=O)C1=CN=CC(C(O)=O)=C1 MPFLRYZEEAQMLQ-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000005907 ketalization reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- 229940101209 mercuric oxide Drugs 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QQXPSPWWWCQBFM-RMKNXTFCSA-N methyl (2e)-2-[(2,3-dichlorophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(\C(C)=O)=C\C1=CC=CC(Cl)=C1Cl QQXPSPWWWCQBFM-RMKNXTFCSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- CSYNQJPENMOLHR-UHFFFAOYSA-N n,n-diethylethanamine;ethyl acetate Chemical compound CCOC(C)=O.CCN(CC)CC CSYNQJPENMOLHR-UHFFFAOYSA-N 0.000 description 1
- IJDIONYCFIJYLK-UHFFFAOYSA-N n,n-diethylethanamine;propan-2-ol Chemical compound CC(C)O.CCN(CC)CC IJDIONYCFIJYLK-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003810 piperidione Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- 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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Photoreceptors In Electrophotography (AREA)
- Coloring (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Laminated Bodies (AREA)
- Preventing Corrosion Or Incrustation Of Metals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8604685A FR2596760B1 (fr) | 1986-04-02 | 1986-04-02 | Derives dissymetriques de l'acide 1,4-dihydropyridine-3,5-dicarboxylique, procedes de preparation et utilisation en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD278793A5 true DD278793A5 (de) | 1990-05-16 |
Family
ID=9333794
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD87325139A DD278793A5 (de) | 1986-04-02 | 1987-04-01 | Verfahren zur herstellung eines unsymmetrischen ester-derivates der 1,4-dihydropyridin-3,5-dicarbonsaeure |
| DD87301364A DD263291A5 (de) | 1986-04-02 | 1987-04-01 | Verfahren zur herstellung eines unsymmetrischen, heterocyclischen ester-derivaten |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD87301364A DD263291A5 (de) | 1986-04-02 | 1987-04-01 | Verfahren zur herstellung eines unsymmetrischen, heterocyclischen ester-derivaten |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US4806544A (cs) |
| EP (1) | EP0240398B1 (cs) |
| JP (1) | JPS6317883A (cs) |
| KR (1) | KR900005956B1 (cs) |
| CN (1) | CN1015460B (cs) |
| AT (1) | ATE63555T1 (cs) |
| AU (2) | AU590690B2 (cs) |
| CS (1) | CS268828B2 (cs) |
| DD (2) | DD278793A5 (cs) |
| DE (1) | DE3770037D1 (cs) |
| DK (1) | DK161787A (cs) |
| ES (1) | ES2028886T3 (cs) |
| FI (1) | FI86302C (cs) |
| FR (1) | FR2596760B1 (cs) |
| GR (1) | GR3002267T3 (cs) |
| HU (2) | HU199479B (cs) |
| IL (1) | IL81933A (cs) |
| NO (1) | NO167029C (cs) |
| NZ (1) | NZ219758A (cs) |
| OA (1) | OA08508A (cs) |
| PT (1) | PT84560B (cs) |
| SU (1) | SU1586515A3 (cs) |
| TN (1) | TNSN87043A1 (cs) |
| YU (2) | YU57287A (cs) |
| ZA (1) | ZA872258B (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4092406D2 (en) * | 1989-12-22 | 1993-04-01 | Byk Gulden Lomberg Chem Fab | Neue dihydropyridine |
| DE4125271A1 (de) * | 1991-07-31 | 1993-02-11 | Bayer Ag | Neue n-alkylierte 1,4-dihydropyridindicarbonsaeureester |
| WO1993006082A1 (en) * | 1991-09-13 | 1993-04-01 | Merck & Co., Inc. | Process for the preparation of 4-substituted-1,4-dihydropyridines |
| EP2410854B1 (en) | 2009-03-27 | 2016-06-29 | Council of Scientific & Industrial Research | Substituted 1, 4-dioxa-8-azaspiro ý4,5¨decanes useful as fungicides and a process for the preparation thereof |
| WO2012123966A1 (en) | 2011-03-04 | 2012-09-20 | Arch Pharmalabs Limited | Process for the preparation of 4 -substituted -1, 4-dihydropyridines |
| CN102796111B (zh) * | 2012-09-10 | 2014-09-24 | 贵州大学 | 氧氮杂螺环酰胺基团的羧(磺)酸酯类化合物及制备方法和用途 |
| CN104860873A (zh) * | 2015-05-28 | 2015-08-26 | 石家庄学院 | 一种(s)-1,4-二氢吡啶钙离子拮抗剂的制备方法 |
| WO2017063307A1 (zh) * | 2015-10-13 | 2017-04-20 | 山东轩竹医药科技有限公司 | 1，4-二氢吡啶-3，5-二羧酸酯衍生物的制备方法及中间体 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670824C3 (de) * | 1967-03-20 | 1978-08-03 | Bayer Ag, 5090 Leverkusen | 1,4-Dihydropyridin-33-dicarbonsäurealkylester |
| GB1245087A (en) * | 1967-10-26 | 1971-09-02 | Wyeth John & Brother Ltd | Heterocyclic compounds |
| JPS4932542B1 (cs) * | 1970-08-17 | 1974-08-31 | ||
| GB1591089A (en) * | 1976-12-17 | 1981-06-10 | Fujisawa Pharmaceutical Co | 1,4-dihydropyridine derivatives and process for preparation thereof |
| US4250312A (en) * | 1979-12-28 | 1981-02-10 | Argus Chemical Corp. | Process for preparing 4-piperidone spiroketal compounds |
| US4250313A (en) * | 1980-02-01 | 1981-02-10 | Argus Chemical Corp. | Process for preparing 4-piperidone spiroketal compounds |
| DE3208628A1 (de) * | 1982-03-10 | 1983-09-22 | Bayer Ag, 5090 Leverkusen | Neue verbindungen, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| WO1983003249A1 (fr) * | 1982-03-17 | 1983-09-29 | Yoshitomi Pharmaceutical | Derives de 1,4-dihydropyridine-3,5-dicarboxylate |
| JPS58159462A (ja) * | 1982-03-17 | 1983-09-21 | Yoshitomi Pharmaceut Ind Ltd | １，４−ジヒドロピリジン−３，５−ジカルボン酸エステル誘導体 |
| FR2577552B1 (fr) * | 1985-02-20 | 1987-09-04 | Sori Soc Rech Ind | Esters heterocycliques dissymetriques d'acides 1,4-dihydropyridine-3,5-dicarboxyliques, procede de preparation et utilisation en therapeutique |
-
1986
- 1986-04-02 FR FR8604685A patent/FR2596760B1/fr not_active Expired
-
1987
- 1987-03-18 EP EP87400598A patent/EP0240398B1/fr not_active Expired - Lifetime
- 1987-03-18 IL IL81933A patent/IL81933A/xx unknown
- 1987-03-18 US US07/027,262 patent/US4806544A/en not_active Expired - Fee Related
- 1987-03-18 DE DE8787400598T patent/DE3770037D1/de not_active Expired - Fee Related
- 1987-03-18 AT AT87400598T patent/ATE63555T1/de not_active IP Right Cessation
- 1987-03-18 ES ES198787400598T patent/ES2028886T3/es not_active Expired - Lifetime
- 1987-03-19 AU AU70410/87A patent/AU590690B2/en not_active Ceased
- 1987-03-24 NZ NZ219758A patent/NZ219758A/xx unknown
- 1987-03-25 FI FI871316A patent/FI86302C/fi not_active IP Right Cessation
- 1987-03-25 TN TNTNSN87043A patent/TNSN87043A1/fr unknown
- 1987-03-26 PT PT84560A patent/PT84560B/pt not_active IP Right Cessation
- 1987-03-27 ZA ZA872258A patent/ZA872258B/xx unknown
- 1987-03-30 DK DK161787A patent/DK161787A/da not_active IP Right Cessation
- 1987-03-31 OA OA59099A patent/OA08508A/xx unknown
- 1987-03-31 NO NO871339A patent/NO167029C/no unknown
- 1987-04-01 CS CS872292A patent/CS268828B2/cs unknown
- 1987-04-01 HU HU871403A patent/HU199479B/hu unknown
- 1987-04-01 DD DD87325139A patent/DD278793A5/de not_active IP Right Cessation
- 1987-04-01 YU YU00572/87A patent/YU57287A/xx unknown
- 1987-04-01 KR KR1019870003078A patent/KR900005956B1/ko not_active Expired
- 1987-04-01 CN CN87102452A patent/CN1015460B/zh not_active Expired
- 1987-04-01 SU SU874202348A patent/SU1586515A3/ru active
- 1987-04-01 HU HU893897A patent/HUT53080A/hu unknown
- 1987-04-01 DD DD87301364A patent/DD263291A5/de not_active IP Right Cessation
- 1987-04-02 JP JP62083694A patent/JPS6317883A/ja active Pending
-
1988
- 1988-03-09 YU YU480/88A patent/YU44714B/xx unknown
- 1988-09-22 US US07/249,402 patent/US4900833A/en not_active Expired - Fee Related
-
1989
- 1989-09-11 AU AU41263/89A patent/AU610753B2/en not_active Ceased
-
1991
- 1991-07-05 GR GR91400959T patent/GR3002267T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ENJ | Ceased due to non-payment of renewal fee |