CA2536608C - Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs - Google Patents

Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs Download PDF

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Publication number: CA2536608C
Authority: CA; Canada
Prior art keywords: carbon atoms; chain; straight; branched alkyl; phenyl
Prior art date: 1994-12-05
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 - Fee Related

Application number

CA002536608A

Other languages

English (en)

Other versions

CA2536608A1 (fr

Inventor

Joachim Mittendorf

Peter Fey

Bodo Junge

Johannes Kaulen

Kai Van Laak

Heinrich Meier

Rudolf Schohe-Loop

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Pharma AG

Original Assignee

Bayer AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-12-05

Filing date

1995-12-01

Publication date

2007-11-20

1994-12-05 Priority claimed from DE4443168A external-priority patent/DE4443168A1/de

1995-12-01 Application filed by Bayer AG filed Critical Bayer AG

1996-06-06 Publication of CA2536608A1 publication Critical patent/CA2536608A1/fr

2007-11-20 Application granted granted Critical

2007-11-20 Publication of CA2536608C publication Critical patent/CA2536608C/fr

2015-12-01 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

-1 phenyl-substituted 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class 0.000 title claims abstract description 23
238000002360 preparation method Methods 0.000 title claims abstract description 10
238000000034 method Methods 0.000 title description 26
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 37
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
125000001424 substituent group Chemical group 0.000 claims abstract description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims abstract description 9
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims abstract description 6
150000003839 salts Chemical class 0.000 claims abstract description 6
125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
125000006193 alkinyl group Chemical group 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 4
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
150000001875 compounds Chemical class 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 13
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 12
239000000203 mixture Substances 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
239000000243 solution Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
150000003923 2,5-pyrrolediones Chemical class 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
150000003863 ammonium salts Chemical class 0.000 description 4
239000012043 crude product Substances 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
XFRBXZCBOYNMJP-UHFFFAOYSA-N 2,2,6-trimethyl-1,3-dioxin-4-one Chemical compound CC1=CC(=O)OC(C)(C)O1 XFRBXZCBOYNMJP-UHFFFAOYSA-N 0.000 description 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
239000007832 Na2SO4 Substances 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
150000002430 hydrocarbons Chemical class 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
IQPINWFJWRBQRY-UHFFFAOYSA-N 2,2,6-triethyl-1,3-dioxin-4-one Chemical compound CCC1=CC(=O)OC(CC)(CC)O1 IQPINWFJWRBQRY-UHFFFAOYSA-N 0.000 description 1
LIALQTZNSARKNP-UHFFFAOYSA-N 2-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CCN=C=NC(C)CN(C)C LIALQTZNSARKNP-UHFFFAOYSA-N 0.000 description 1
MVYGQIWGZGMFAU-UHFFFAOYSA-N 2-chloro-3-formylbenzonitrile Chemical compound ClC1=C(C=O)C=CC=C1C#N MVYGQIWGZGMFAU-UHFFFAOYSA-N 0.000 description 1
CRPFKUKPDCBUIX-UHFFFAOYSA-N 2-ethyl-5-phenyl-1,2-oxazol-2-ium-3-sulfonate Chemical compound [O-]S(=O)(=O)C1=[N+](CC)OC(C=2C=CC=CC=2)=C1 CRPFKUKPDCBUIX-UHFFFAOYSA-N 0.000 description 1
XJOLYWNYMOPRKQ-WAYWQWQTSA-N 2-methoxyethyl (z)-3-aminobut-2-enoate Chemical compound COCCOC(=O)\C=C(\C)N XJOLYWNYMOPRKQ-WAYWQWQTSA-N 0.000 description 1
UIENECRHSIJLDI-UHFFFAOYSA-N 2-methoxyethyl 2-[(2-chloro-3-cyanophenyl)methylidene]-3-oxobutanoate Chemical compound COCCOC(=O)C(C(C)=O)=CC1=CC=CC(C#N)=C1Cl UIENECRHSIJLDI-UHFFFAOYSA-N 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 1
GTIKSQYSAKETQA-LJQANCHMSA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4r)-4-(2-chloro-3-cyanophenyl)-2,6-dimethyl-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(C#N)=C1Cl GTIKSQYSAKETQA-LJQANCHMSA-N 0.000 description 1
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
XIGCUCWPRLAFFR-UHFFFAOYSA-N 4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class OC(=O)C1=CNC=C(C(O)=O)C1C1=CC=CC=C1 XIGCUCWPRLAFFR-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
150000001243 acetic acids Chemical class 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000006399 behavior Effects 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 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
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
239000003814 drug Substances 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1

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Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002536608A 1994-12-05 1995-12-01 Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs Expired - Fee Related CA2536608C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DEP4443168.6		1994-12-05
DE4443168A DE4443168A1 (de)	1994-12-05	1994-12-05	Neues hochselektives Verfahren zur Herstellung von enantiomerenreinen phenylsubstituierten 1,4-Dihydropyridin-3,5-dicarbonsäurederivaten
CA002164276A CA2164276C (fr)	1994-12-05	1995-12-01	Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002164276A Division CA2164276C (fr)	1994-12-05	1995-12-01	Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs

Publications (2)

Publication Number	Publication Date
CA2536608A1 CA2536608A1 (fr)	1996-06-06
CA2536608C true CA2536608C (fr)	2007-11-20

Family

ID=36283178

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002536608A Expired - Fee Related CA2536608C (fr)	1994-12-05	1995-12-01	Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs

Country Status (1)

Country	Link
CA (1)	CA2536608C (fr)

1995
- 1995-12-01 CA CA002536608A patent/CA2536608C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2536608A1 (fr)	1996-06-06

Legal Events

Date	Code	Title	Description
2006-02-27	EEER	Examination request
2013-01-15	MKLA	Lapsed	Effective date: 20121203

Publication	Publication Date	Title
US5438145A (en)	1995-08-01	Process for the preparation of amlodipine benzenesulphonate
EP0599220B1 (fr)	1996-08-14	Procédé pour la préparation du benzènesulfonate d'amlodipine
EP1125924B1 (fr)	2005-12-21	Produit intermediaire pour la synthese d'amlodipine, et procede de preparation et d'utilisation correspondants
AU596382B2 (en)	1990-05-03	Flavone derivatives
HU204786B (en)	1992-02-28	Process for producing new dihydropyridine amide derivatives and pharmaceutical compositions comprising such compounds
CA2164276C (fr)	2007-04-10	Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs
CA2536608C (fr)	2007-11-20	Methode tres selective pour la preparation de derives de substitution phenyliques d'acide 1,4-dihydropyridine-3,5-dicarboxylique, sous forme d'enantiomeres purs
JPH02149563A (ja)	1990-06-08	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
JP3100444B2 (ja)	2000-10-16	１，４−ジヒドロピリジン誘導体及びその製造方法
US20020132834A1 (en)	2002-09-19	Method for preparing amlodipine
FI94242B (fi)	1995-04-28	Menetelmä heterosyklisten johdannaisten valmistamiseksi
JPH0641063A (ja)	1994-02-15	ピロリジン誘導体
EP0109049A2 (fr)	1984-05-23	Procédé de préparation de dérivés de dihydropyridine et les intermédiaires nécessaires
KR100354806B1 (ko)	2002-10-05	암로디핀 베실레이트의 신규 중간체 및 그의 제조방법
JPH07196612A (ja)	1995-08-01	１，４−ジヒドロピリジン誘導体及びそれを用いる１，４−ジヒドロピリジンカルボン酸誘導体の製造方法
JPH0455426B2 (fr)	1992-09-03