公开(公告)号：US20060217561A1

公开(公告)日：2006-09-28

申请号：US11242640

申请日：2005-10-03

申请人： Mukund Chorghade ,  Rayomand Gimi ,  Peter McDonnell ,  Paul Wolstenholme-Hogg

发明人： Mukund Chorghade ,  Rayomand Gimi ,  Peter McDonnell ,  Paul Wolstenholme-Hogg

IPC分类号： C07D277/14

CPC分类号： C07C227/18 ,  C07B2200/07 ,  C07C229/36 ,  C07C255/53 ,  C07C255/54 ,  C07C257/08 ,  C07C319/02 ,  C07C319/06 ,  C07C319/12 ,  C07C319/20 ,  C07D277/12 ,  C07D303/24 ,  C07C323/58

摘要： A useful and efficient method of preparing an alkylated thiazoline carboxylic acid, or a derivative thereof, comprises coupling a substituted aryl nitrile such as, for example, 2,4-dimethoxybenzonitrile or 4-methoxybenzonitrile, with a cysteine ester to form a substituted thiazoline carboxylic acid ester; optionally hydrolyzing the substituted thiazoline carboxylic acid ester to form a substituted thiazoline carboxylic acid; optionally, protecting the carboxyl group; alkylating the thiazoline ring at the 4-carbon position, as indicated in Structural Formula (I), with a compound of the formula R1-L, wherein R1 is as defined above and L is a leaving group, in the presence of a phase transfer catalyst; and, optionally, deprotecting the carboxyl group. In one embodiment of the present invention, a cinchona-alkaloid derived phase transfer catalyst is used to alkylate a protected substituted thiazoline carboxylic acid.

公开(公告)号：US20060281926A1

公开(公告)日：2006-12-14

申请号：US11508679

申请日：2006-08-23

申请人： Rayomand Gimi ,  Mukund Chorghade

发明人： Rayomand Gimi ,  Mukund Chorghade

IPC分类号： C07D277/10

CPC分类号： C07C227/18 ,  C07B2200/07 ,  C07C229/36 ,  C07C255/53 ,  C07C255/54 ,  C07C257/08 ,  C07C319/02 ,  C07C319/06 ,  C07C319/12 ,  C07C319/20 ,  C07D277/12 ,  C07D303/24 ,  C07C323/58

摘要： Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. In one embodiment, the present invention provides methods of preparing 2-alkylcysteine derivatives. In another embodiment, the method comprises forming a 2-alkylcysteine derivative from a cysteine derivative in the presence of a phase transfer catalyst. In particular, the present invention provides methods for preparing 2-methylcysteine derivatives. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In one aspect, an aryl nitrile or imidate is condensed with cysteine or a 2-alkyl cysteine. The present invention also relates to the preparation of 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-alkyl-thiazole-4-carboxylic acids, such as 4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-thiazole-4-carboxylic acid.