Process to prepare, 1,4-dihydropyridine intermediates and derivatives thereof
First Claim
1. A process for the manufacture of a benzylidene intermediate of formula wherein R1 is C1 to C12 alkyl which is optionally substituted by a C1-C4 alkoxyl, a trifluroromethyl or (C6H5CH2)(CH3)N and X and Y are independently selected from the group consisting of H, C1 to C6 alkyl, C1 to C6 alkoxy, C1 to C6 alkylaryl, halo, aryl, substituted aryl, and nitro, comprising the condensation reaction of an aldehyde of formula
with an acetoacetate of formula
in the presence of catalytic amounts of a pyridyl carboxylic acid of formula
and a secondary amine.
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Accused Products
Abstract
An improved catalyst is disclosed for a process involving the preparation of benzylidene intermediates useful in the preparation of 1,4-dihydropyridine compounds and derivatives thereof useful as medicines such as for example felodipine. This is accomplished by the condensation of an aldehyde and an acetoacetate in the presence of a novel catalyst system that includes a pyridyl carboxylic acid and a secondary amine. It has been found that through the use of the present invention the purity and yield of the desired isomer of the benzylidene intermediate can be maximized, thus avoiding the requirement of additional purification steps. The use of these intermediates can then be further reacted to form the required dihydropyridines, again having a very high purity and yield compared with the prior art.
3 Citations
21 Claims
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1. A process for the manufacture of a benzylidene intermediate of formula
wherein R1 is C1 to C12 alkyl which is optionally substituted by a C1-C4 alkoxyl, a trifluroromethyl or (C6H5CH2)(CH3)N and X and Y are independently selected from the group consisting of H, C1 to C6 alkyl, C1 to C6 alkoxy, C1 to C6 alkylaryl, halo, aryl, substituted aryl, and nitro, comprising the condensation reaction of an aldehyde of formula with an acetoacetate of formula in the presence of catalytic amounts of a pyridyl carboxylic acid of formula and a secondary amine.
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9. A process for the preparation of felodipine comprising:
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(a) the condensation reaction of an aldehyde of formula
with an acetoacetate of formula
in the presence of catalytic amounts of a pyridyl carboxylic acid of formula
and a secondary amine; and
(b) the reaction of the resulting product with an enamine of formula wherein R1 and R2 are methyl and ethyl respectively or ethyl and methyl respectively. - View Dependent Claims (10, 11, 12, 13)
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14. A process for the preparation of nitrendipine comprising:
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(a) the condensation reaction of an aldehyde of formula
with an acetoacetate of formula
in the presence of catalytic amounts of a pyridyl carboxylic acid of formula
and a secondary amine; and
(b) the reaction of the resulting product with an enamine of formula
wherein R1 and R2 are methyl and ethyl respectively or ethyl and methyl respectively. - View Dependent Claims (15, 16, 17, 18)
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Specification
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- Resources
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Current AssigneeApotex Pharmachem India PVT Limited (Apotex Holdings Incorporated)
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Original AssigneeApotex Pharmachem India PVT Limited (Apotex Holdings Incorporated)
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InventorsGuntoori, Bhaskar Reddy, Che, Daqing, Murthy, K. S. Keshava
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Primary Examiner(s)Killos, Paul J.
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Application NumberUS10/819,910Publication NumberTime in Patent Office320 DaysField of Search560/23, 560/51, 560/53, 546/249, 546/321US Class Current560/53CPC Class CodesC07D 211/90 Carbon atoms having three b...
