4-METHYL-2-[1-(TERT-BUTOXYCARBONYL)PIPERID-4-YL]-1,3-THIAZOLE-5-CARBOXYLIC ACID synthesis

Yield:1083418-79-4 25%

Reaction Conditions:

Stage #1: 4-(5-carboxy-4-methyl-thiazol-2-yl)-piperidine-1-carboxylic acid tert-butyl esterwith dmap;1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in dichloromethane; for 0.166667 h;
Stage #2: 3-(2-amino-4-chlorophenyl)-4H-[1,2,4]oxadiazol-5-one in dichloromethane at 20;

Steps:

4-{5-[5-Chloro-2-(5-oxo-4, 5-dihydro-[1 , 2, 4]oxadiazol-3-yl)-phenylcarbamoyl]-4-methyl- thiazol-2-yl}-piperidine-1-carboxylic acid tert-butyl ester (26)To a suspension of commercial 4-(5-carboxy-4-methyl-thiazol-2-yl)- piperidine-1 -carboxylic acid tert-butyl ester (0.25 g, 1 eq) in DCM (10 ml), EDCηCI (0.2937 g, 2 eq) and DMAP (0.2807 g, 3 eq) are added. The resulting solution is stirred for 10 min and 3-(2-amino-4-chloro-phenyl)-4H-[1 ,2,4]oxadiazol-5-one (0.1621 g, 1 eq) (prepared as described by Valgeirsson et al. in Journal of Medicinal Chemistry 2004 47 (27) 6948-6957) is added. The solution is stirred at room 5 temperature overnight, diluted with DCM (20 ml), washed with 1.5 N HCI (30 ml) and water (30 ml), dried and evaporated to dryness, to give a solid residue (-0.370 g) that is purified by preparative LCMS, to afford the title compound as white powder (0.101 g, -25% yield). LC-ESI-HRMS of [M+H]+ shows 520.1411 Da. CaIc. 520.142144 Da, dev. -2 ppm.10

References:

WO2008/138917,2008,A1 Location in patent:Page/Page column 33-34