Abstract: Process for the preparation of Flecainide, its pharmaceutically acceptable salts and important intermediates thereof that involves the use of the 2-halobenzoic acid and its derivatives as a starting material. The use of this process also allows for the synthesis of a novel intermediate useful in the production of Flecainide. This new process is an inexpensive and efficient process for the manufacture of these compounds.
Abstract: A process for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester comprising: (a) reduction of 5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-oxo-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester; (b) hydrolysis of (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester using an alkali base in a solvent to form the acid; (c) alkylation of the acid forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester.
Type:
Grant
Filed:
March 16, 2004
Date of Patent:
March 20, 2007
Assignee:
Apotex Pharmachem Inc.
Inventors:
Bhaskar Reddy Guntoori, Daqing Che, Fan Wang, Yajun Zhao, K. S. Keshava Murthy, Stephen E. Horne
Abstract: A process for the industrial scale manufacture of 4-(4-fluorophenyl)-N-alkylnipecotinate esters by the addition of 4-fluorophenylmagnesium halide in tetrahydrofuran to 3,4-unsaturated-3-piperidine esters.
Type:
Grant
Filed:
May 17, 2002
Date of Patent:
November 21, 2006
Assignee:
Apotex Pharmachem Inc.
Inventors:
Allan W. Rey, K. S. Keshava Murthy, Bruno K. Radatus, Yajun Zhao, Tania E. Nish
Abstract: A process for preparing Oxcarbazepine III comprising: a) reacting oximinostilbene IV ?with chlorosulfonyl isocyanate in an inert organic solvent and isolating compound V b) hydrolyzing compound V to form crude Oxcarbazepine III c) purifying oxcarbazepine.
Type:
Grant
Filed:
June 16, 2005
Date of Patent:
October 24, 2006
Assignee:
Apotex Pharmachem Inc.
Inventors:
Daqing Che, Nadia Corelli-Rennie, Bhaskar Reddy Guntoori, Jodi Faught
Abstract: A process is provided for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 comprising: (a) reacting the aldehyde 1 with the enolate form of (S)-2-hydroxy-1,2,2-triphenylethyl acetate substituent in a chelating co-solvent; (b) hydrolysis of (R,S)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (S)-2-hydroxy-1,2,2-triphenylethyl ester (2a and 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the carboxylic acid 7; (c) treating the acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt; (d) alkylation of the (R)-7 chiral base salt or the free base derived from (R)-7, forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid,
Type:
Grant
Filed:
April 6, 2005
Date of Patent:
September 26, 2006
Assignee:
Apotex Pharmachem Inc.
Inventors:
Fan Wang, Daqing Che, Bhaskar Reddy Guntoori, Yajun Zhao, Aaron C. Kinsman, Jody Faught, Alan Chow
Abstract: The present invention relates to new and useful processes for the preparation of the anhydrate form of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride.
Type:
Grant
Filed:
August 30, 2004
Date of Patent:
August 8, 2006
Assignee:
Apotex Pharmachem Inc.
Inventors:
Carlos Zetina-Rocha, Allan W. Rey, Stephen E. Horne
Abstract: A process for the preparation of tetrahydrothieno[3,2-c]pyridine compound of formula 6: or their pharmaceutically acceptable salts, wherein the meaning of X is carboxyl, alkoxycarbonyl, aryloxycarbonyl, or carbamoyl of formula wherein R1 and R2 can be individually or simultaneously hydrogen, alkyl or part of a heterocyclic structure; Z can be hydrogen, halogen, alkyl, aryl, aryloxy or alkoxy group, the process comprising conducting a dehydroxylation reaction on the compound of formula 5 in order to obtain a compound of formula 6, wherein said dehydroxylation reaction is effected by iodosilane represented by the formula Si(R3)3I, wherein R3 selected from an alkyl, alkenyl, alkynyl, aromatic group, or combinations of thereof
Abstract: A process for the preparation of a polypeptide designated in the present invention as 1, composed of the following amino acid units in the structure, namely: L-alanine, L-glutamic acid, L-lysine and L-tyrosine randomly arranged in the polypeptide 1, or pharmaceutically acceptable salts thereof, comprising the steps of: (a) polymerization of a mixture of the N-carboxyanhydrides of L-alanine, L-tyrosine, a protected L-glutamate and a protected L-lysine to obtain protected copolymer 6 or salt thereof; (b) deprotection of the protected copolymer 6 (or salt thereof) to produce polypeptide 1 or a pharmaceutically acceptable salt thereof in one single step; (c) separation and purification of the polypeptide 1 (or a pharmaceutically acceptable salt) to obtain a purified polypeptide 1
Type:
Grant
Filed:
December 24, 2002
Date of Patent:
May 23, 2006
Assignee:
Apotex Pharmachem Inc.
Inventors:
Elena Bejan, Gamini Weeratunga, Stephen E. Horne
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.
Type:
Grant
Filed:
April 8, 2004
Date of Patent:
February 22, 2005
Assignee:
Apotex Pharmachem Inc.
Inventors:
Daqing Che, Bhaskar Reddy Guntoori, K. S. Keshava Murthy