IL103010A - Preparation of 1,4-converted dihydropyridines - Google Patents

Preparation of 1,4-converted dihydropyridines

Info

Publication number: IL103010A
Authority: IL; Israel
Prior art keywords: dam48; alkyl; compound; hydrogen; formula
Prior art date: 1991-09-13

Application number

IL10301092A

Other languages

English (en)

Hebrew (he)

Other versions

IL103010A0 (en

Original Assignee

Merck & Co Inc

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.)

1991-09-13

Filing date

1992-09-01

Publication date

1996-10-31

1992-07-28 Priority claimed from US07/920,701 external-priority patent/US5310917A/en

1992-09-01 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1993-02-21 Publication of IL103010A0 publication Critical patent/IL103010A0/xx

1996-10-31 Publication of IL103010A publication Critical patent/IL103010A/en

Links

-1 4-substituted-1,4- dihydropyridines Chemical class 0.000 title claims abstract description 13
238000002360 preparation method Methods 0.000 title claims description 22
239000002253 acid Substances 0.000 claims abstract description 34
229960003580 felodipine Drugs 0.000 claims abstract description 34
RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims abstract description 33
YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 claims abstract description 10
238000001914 filtration Methods 0.000 claims abstract description 10
238000000034 method Methods 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 34
239000002904 solvent Substances 0.000 claims description 32
239000011541 reaction mixture Substances 0.000 claims description 27
150000001875 compounds Chemical class 0.000 claims description 26
238000010438 heat treatment Methods 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
238000001816 cooling Methods 0.000 claims description 6
125000004188 dichlorophenyl group Chemical group 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 claims description 3
UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 claims description 3
101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 claims description 3
101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 claims description 3
101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 claims description 3
101150111293 cor-1 gene Proteins 0.000 claims description 3
229960004340 lacidipine Drugs 0.000 claims description 3
GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 claims description 3
VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 claims description 3
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 3
229960001597 nifedipine Drugs 0.000 claims description 3
229960005366 nilvadipine Drugs 0.000 claims description 3
229960000715 nimodipine Drugs 0.000 claims description 3
229960000227 nisoldipine Drugs 0.000 claims description 3
229960005425 nitrendipine Drugs 0.000 claims description 3
LBSRZVRITCRLIU-UHFFFAOYSA-N 3-o-ethyl 5-o-(2-piperidin-1-ylethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCCCC2)C1C1=CC=CC([N+]([O-])=O)=C1 LBSRZVRITCRLIU-UHFFFAOYSA-N 0.000 claims description 2
BFLVNSZFGLVPLU-UHFFFAOYSA-N 3-o-methyl 5-o-[[5-(piperidin-1-ylmethyl)furan-2-yl]methyl] 4-(2-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC=2OC(CN3CCCCC3)=CC=2)C1C1=CC=CC=C1F BFLVNSZFGLVPLU-UHFFFAOYSA-N 0.000 claims description 2
CNIJVNPIIHWRRP-WKDCXCOVSA-N 5-o-[[8-(4-chlorophenyl)-1,4-dioxa-8-azaspiro[4.5]decan-3-yl]methyl] 3-o-methyl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OCC2OC3(CCN(CC3)C=3C=CC(Cl)=CC=3)OC2)=CC=CC([N+]([O-])=O)=C1 CNIJVNPIIHWRRP-WKDCXCOVSA-N 0.000 claims description 2
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 claims description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
229960002992 barnidipine Drugs 0.000 claims description 2
VXMOONUMYLCFJD-DHLKQENFSA-N barnidipine Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@@H]2CN(CC=3C=CC=CC=3)CC2)=CC=CC([N+]([O-])=O)=C1 VXMOONUMYLCFJD-DHLKQENFSA-N 0.000 claims description 2
229950000309 cronidipine Drugs 0.000 claims description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 2
229960003963 manidipine Drugs 0.000 claims description 2
ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 claims description 2
229960001783 nicardipine Drugs 0.000 claims description 2
229950010959 sagandipine Drugs 0.000 claims description 2
FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 claims 2
125000003710 aryl alkyl group Chemical group 0.000 claims 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 1
230000000630 rising effect Effects 0.000 claims 1
238000006243 chemical reaction Methods 0.000 abstract description 26
238000006352 cycloaddition reaction Methods 0.000 abstract description 6
238000007363 ring formation reaction Methods 0.000 abstract description 3
229940124549 vasodilator Drugs 0.000 abstract description 2
239000003071 vasodilator agent Substances 0.000 abstract description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
239000000243 solution Substances 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 20
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
239000000047 product Substances 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
238000004128 high performance liquid chromatography Methods 0.000 description 11
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
229960004592 isopropanol Drugs 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
238000007171 acid catalysis Methods 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
239000012535 impurity Substances 0.000 description 6
238000010626 work up procedure Methods 0.000 description 6
239000011260 aqueous acid Substances 0.000 description 5
239000012300 argon atmosphere Substances 0.000 description 5
229940098779 methanesulfonic acid Drugs 0.000 description 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
238000002955 isolation Methods 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000007789 gas Substances 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
239000011707 mineral Substances 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
238000010899 nucleation Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
LLMLNAVBOAMOEE-UHFFFAOYSA-N 2,3-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1Cl LLMLNAVBOAMOEE-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
150000003934 aromatic aldehydes Chemical class 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
UKVYVZLTGQVOPX-IHWYPQMZSA-N (z)-3-aminobut-2-enoic acid Chemical class C\C(N)=C\C(O)=O UKVYVZLTGQVOPX-IHWYPQMZSA-N 0.000 description 1
MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
TVHJYCAIPMCLKS-UHFFFAOYSA-N 3,5-diethyl-1,2-dihydropyridine Chemical compound CCC1=CC(CC)=CNC1 TVHJYCAIPMCLKS-UHFFFAOYSA-N 0.000 description 1
CTAANKPFWDAPSQ-UHFFFAOYSA-N 3,5-dimethyl-1,2-dihydropyridine Chemical compound CC1=CC(C)=CNC1 CTAANKPFWDAPSQ-UHFFFAOYSA-N 0.000 description 1
ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000003935 benzaldehydes Chemical class 0.000 description 1
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 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
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
239000000480 calcium channel blocker Substances 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
229940106681 chloroacetic acid Drugs 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
AOUWUICQFLPQPK-UHFFFAOYSA-N cyclopropyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC1CC1 AOUWUICQFLPQPK-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
229960005215 dichloroacetic acid Drugs 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
PBWZKZYHONABLN-UHFFFAOYSA-N difluoroacetic acid Chemical compound OC(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-N 0.000 description 1
125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000012035 limiting reagent Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
238000007040 multi-step synthesis reaction Methods 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
230000007935 neutral effect Effects 0.000 description 1
KJWGEXJCWCYEMI-UHFFFAOYSA-N nilvadipine Chemical compound COC(=O)C1=C(C#N)N=C(C)C(C(=O)OC(C)C)C1C1=CC=CC(N(=O)=O)=C1 KJWGEXJCWCYEMI-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229940074355 nitric acid Drugs 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000002002 slurry Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
229960004319 trichloroacetic acid Drugs 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

IL10301092A 1991-09-13 1992-09-01 Preparation of 1,4-converted dihydropyridines IL103010A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US75902691A	1991-09-13	1991-09-13
US07/920,701 US5310917A (en)	1991-09-13	1992-07-28	Process for the preparation of 4-substituted-1,4-dihydropydrines

Publications (2)

Publication Number	Publication Date
IL103010A0 IL103010A0 (en)	1993-02-21
IL103010A true IL103010A (en)	1996-10-31

Family

ID=27116618

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10301092A IL103010A (en)	1991-09-13	1992-09-01	Preparation of 1,4-converted dihydropyridines

Country Status (15)

Country	Link
EP (1)	EP0534520B1 (de)
JP (1)	JPH0751562B2 (de)
CN (1)	CN1070907A (de)
AT (1)	ATE150456T1 (de)
AU (1)	AU654387B2 (de)
CA (1)	CA2077919A1 (de)
DE (1)	DE69218330T2 (de)
DK (1)	DK0534520T3 (de)
ES (1)	ES2101027T3 (de)
GR (1)	GR3022877T3 (de)
IL (1)	IL103010A (de)
LV (1)	LV12072B (de)
MX (1)	MX9205215A (de)
NZ (1)	NZ244130A (de)
WO (1)	WO1993006082A1 (de)

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DE4342196A1 (de) *	1993-12-10	1995-06-14	Bayer Ag	Neue 4-Phenyl-substituierte 1,4-Dihydropyridine
EP0657432B1 (de)	1993-12-10	2003-03-12	Bayer Ag	Phenyl-substituierte 1,4-Dihydropyridine mit cerebraler Aktivität
DE4423445A1 (de) *	1994-07-05	1996-01-11	Bayer Ag	Katalysatorverfahren zur Herstellung von Nifedipin
US5554621A (en) *	1995-06-07	1996-09-10	Bristol-Myers Squibb Company	Dihydropyridine NPY antagonists: nitrogen heterocyclic derivatives
US5668151A (en) *	1995-06-07	1997-09-16	Bristol-Myers Squibb Company	Dihydropyridine NPY antagonists: piperidine derivatives
US5977369A (en) *	1995-12-28	1999-11-02	Napp Technologies, Inc.	Process to prepare dihydropyridine and derivatives thereof
IT1283793B1 (it) *	1996-08-23	1998-04-30	Lusochimica Spa	Processo per la preparazione di diidropiridine
US5889016A (en) *	1997-06-26	1999-03-30	Bristol-Myers Squibb Company	Dihydropyrimidone derivatives as NPY antagonists
HUP9900353A3 (en) *	1999-02-15	2002-01-28	Egis Gyogyszergyar Nyilvanosan	Process for producing asymmetric esters of 1,4-dihydropyridine-dicarboxylic acids
RU2161156C1 (ru) *	1999-06-01	2000-12-27	Джи.Б.Кемикалс Энд Фармасьютикалс Лтд	Способ получения 3-этил-5-метиловый эфир 2-[2-(n-фталимидо)-этоксиметил]-4-(2-хлорфенил)-1,4-дигидро-6-метил-3,5- пиридиндикарбоновой кислоты
EP1202738A4 (de)	1999-06-21	2002-08-14	Bristol Myers Squibb Co	Dihydropyrazin derivate als npy antagonisten
PL362660A1 (en)	2000-12-29	2004-11-02	Pfizer Limited	Process for making amlodipine maleate
US7335380B2 (en)	2000-12-29	2008-02-26	Synthon Ip Inc.	Amlodipine free base
AT5874U1 (de)	2000-12-29	2003-01-27	Bioorg Bv	Pharmazeutische zubereitungen enthaltend amlodipinmaleat
EP1309557B9 (de)	2000-12-29	2006-11-15	Pfizer Limited	Amlodipin-hemimaleat
WO2002053540A1 (en)	2000-12-29	2002-07-11	Pfizer Limited	Aspartate derivative of amlodipine as calcium channel antagonist
US6653481B2 (en)	2000-12-29	2003-11-25	Synthon Bv	Process for making amlodipine
EP1309556B1 (de)	2000-12-29	2004-11-24	Pfizer Limited	Amlodipinfumarat
WO2002054062A2 (en)	2000-12-29	2002-07-11	Pfizer Limited	Reference standards and processes for determining the purity or stability of amlodipine maleate
CA2433193C (en)	2000-12-29	2006-01-31	Pfizer Limited	Amide derivative of amlodipine
MXPA03005882A (es)	2000-12-29	2005-04-19	Pfizer Ltd	Derivado amida de amlodipina.
WO2010039977A2 (en)	2008-10-01	2010-04-08	Amira Pharmaceuticals, Inc.	Heteroaryl antagonists of prostaglandin d2 receptors
CN101613280B (zh) *	2009-05-13	2012-10-17	合肥立方制药股份有限公司	非洛地平合成中间体2,3-二氯亚苄基乙酰乙酸甲酯的制备方法
CN103951608B (zh) *	2009-08-04	2016-04-27	喜德生（苏州）医药科技有限公司	尼伐地平晶型及其制备方法
WO2012123966A1 (en)	2011-03-04	2012-09-20	Arch Pharmalabs Limited	Process for the preparation of 4 -substituted -1, 4-dihydropyridines
CN102285911B (zh) *	2011-07-12	2015-06-17	绍兴文理学院	非洛地平的制备方法
CN102304079B (zh) *	2011-09-29	2013-09-25	合肥立方制药股份有限公司	一种非洛地平环合反应液直接水析纯化方法
US8889730B2 (en)	2012-04-10	2014-11-18	Pfizer Inc.	Indole and indazole compounds that activate AMPK
EP2970177A1 (de)	2013-03-15	2016-01-20	Pfizer Inc.	Indolverbindungen zur ampk-aktivierung

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DK224786A (da) *	1985-06-21	1986-12-22	Hoffmann La Roche	Dihydropyridinderivater
US4780538A (en) *	1986-02-12	1988-10-25	Merck & Co., Inc.	Process for 1,4-dihydropyridine compounds using a titanamine catalyst
FR2596760B1 (fr) *	1986-04-02	1988-12-09	Sori Soc Rech Ind	Derives dissymetriques de l'acide 1,4-dihydropyridine-3,5-dicarboxylique, procedes de preparation et utilisation en therapeutique
JPH02149563A (ja) *	1988-11-30	1990-06-08	Nisshin Flour Milling Co Ltd	２−ハロエトキシカルボニル基を含有する１，４−ジヒドロピリジン誘導体の製造法
JPH04211060A (ja) *	1990-03-07	1992-08-03	Tokawa Tetsuo	２，６−ジメチル−４−（ｍ−ニトロフェニル）−１，４−ジヒドロピリジン−３，５−ジカルボン酸−３−メチルエステル−５−β−（Ｎ−ベンジル−Ｎ−メチルアミノ）エチルエステルの新規製造方法
DE4011695A1 (de) *	1990-04-11	1991-10-17	Bayer Ag	Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsaeureestern als arzneimittel, neue verbindungen und verfahren zu ihrer herstellung

1992
- 1992-08-26 WO PCT/US1992/007220 patent/WO1993006082A1/en not_active Ceased
- 1992-08-28 NZ NZ244130A patent/NZ244130A/en unknown
- 1992-09-01 IL IL10301092A patent/IL103010A/en not_active IP Right Cessation
- 1992-09-05 DK DK92202690.1T patent/DK0534520T3/da active
- 1992-09-05 DE DE69218330T patent/DE69218330T2/de not_active Expired - Fee Related
- 1992-09-05 EP EP92202690A patent/EP0534520B1/de not_active Expired - Lifetime
- 1992-09-05 AT AT92202690T patent/ATE150456T1/de not_active IP Right Cessation
- 1992-09-05 ES ES92202690T patent/ES2101027T3/es not_active Expired - Lifetime
- 1992-09-07 JP JP4238429A patent/JPH0751562B2/ja not_active Expired - Fee Related
- 1992-09-10 CA CA002077919A patent/CA2077919A1/en not_active Abandoned
- 1992-09-11 CN CN92110385.9A patent/CN1070907A/zh active Pending
- 1992-09-11 MX MX9205215A patent/MX9205215A/es not_active IP Right Cessation
- 1992-09-11 AU AU23552/92A patent/AU654387B2/en not_active Ceased
1997
- 1997-03-20 GR GR970400486T patent/GR3022877T3/el unknown
1998
- 1998-03-06 LV LVP-98-44A patent/LV12072B/en unknown

Also Published As

Publication number	Publication date
ATE150456T1 (de)	1997-04-15
CN1070907A (zh)	1993-04-14
LV12072B (en)	1998-09-20
JPH0751562B2 (ja)	1995-06-05
AU2355292A (en)	1993-03-18
DE69218330T2 (de)	1997-09-18
GR3022877T3 (en)	1997-06-30
LV12072A (lv)	1998-06-20
DE69218330D1 (de)	1997-04-24
DK0534520T3 (da)	1997-09-08
ES2101027T3 (es)	1997-07-01
EP0534520B1 (de)	1997-03-19
MX9205215A (es)	1993-03-01
JPH05221984A (ja)	1993-08-31
IL103010A0 (en)	1993-02-21
NZ244130A (en)	1994-10-26
WO1993006082A1 (en)	1993-04-01
CA2077919A1 (en)	1993-03-14
EP0534520A2 (de)	1993-03-31
EP0534520A3 (en)	1993-05-05
AU654387B2 (en)	1994-11-03

Legal Events

Date	Code	Title
1997-03-18	FF	Patent granted
1997-07-13	KB	Patent renewed
1999-01-26	KB	Patent renewed
2002-11-10	KB	Patent renewed
2007-07-24	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0534520B1 (de)	1997-03-19	Verfahren zur Herstellung von an 4-Position substituierten 1,4-Dihydropyridinen
EP1799644B1 (de)	2014-02-12	Lercanidipinsalze
US5389654A (en)	1995-02-14	3-ethyl 5-methyl(±)2-[2-(N-tritylamino)ethoxymethyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-6-methyl-3,5-pyridinedicarboxylate
EP0599220B1 (de)	1996-08-14	Verfahren zur Herstellung von amlodipin-Benzolsulfonat
EP1125924B1 (de)	2005-12-21	Zwischenstufe für die synthese von amlodipin, herstellungsverfahren und entsprechende anwendung
AU777565B2 (en)	2004-10-21	Process for preparing amlodipine benzenesulphonate
US5310917A (en)	1994-05-10	Process for the preparation of 4-substituted-1,4-dihydropydrines
JPH08295678A (ja)	1996-11-12	１−（フェニル）−１−ヒドロキシ−２−アミノ−３−フルオロプロパン誘導体製造用中間体
CA2425561C (en)	2007-09-18	Process to prepare 1,4-dihydropyridine intermediates and derivatives thereof
NO166712B (no)	1991-05-21	Fremgangsmaate ved fremstilling av pyrrolidonderivater.
JPH0521105B2 (de)	1993-03-23
KR100646670B1 (ko)	2006-11-23	레르카니디핀 염화수소의 개선된 제조방법
Valenti et al.	1998	Coumarin 1, 4-dihydropyridine derivatives
KR930001404B1 (ko)	1993-02-27	디아릴 화합물의 제조방법
NO842092L (no)	1984-11-28	Fremgangsmaate for fremstilling av 2,6-disubstituerte-1,4-dihydropyridin-derivater
RU2146672C1 (ru)	2000-03-20	Способ получения 3-этил-5-метил(±)2[2-аминоэтокси)-метил]-4-(2-хлорфенил)-1,4-дигидро- 6-метил-3,5-пиридиндикарбоксилат монобензолсульфоната
CA1261338A (en)	1989-09-26	Esters of 1,4-dihydro-2,6-dimethyl-3-(alkoxycarbonyl or alkoxyalkoxycarbonyl)-4-(substituted phenyl)- pyridine-5-carboxylic acid
KR100469030B1 (ko)	2005-01-31	시사프라이드의 합성방법
KR910001440B1 (ko)	1991-03-07	2-(N-벤질-N-메틸아미노)에틸메틸 2,6-디메틸-4-(m-니트로페닐)-1,4-디히드로피리딘-3,5-디카르복실레이트 및 그의 염산염의 제조방법
CA1067496A (en)	1979-12-04	1-(2-cyano-ethyl)-1,2,3,4,6,7-hexahydro-12h-indolo(2,3-a) quinolizino compounds
JPH07126251A (ja)	1995-05-16	１、４−ジヒドロピリジンモノカルボン酸類の製造方法
JPH0155268B2 (de)	1989-11-22
KR100559800B1 (ko)	2006-03-10	메틸1,1,질소-트리메틸-(3,3-디페닐프로필)-2-아미노에틸-1,4-디하이드로-2,6-디메틸-4(3-니트로페닐)-피리딘-3,5-디카르복실레이트 하이드로클로라이드의 새로운 제조방법
RS49947B (sr)	2008-09-29	Postupak za sintezu 1,4-dihidropiridinskih derivata
JPH0527624B2 (de)	1993-04-21