新产品编号:489347

Chemical Name: (6S,8aS)-N-[1(S)-(1-Carbamimidoylpiperidin-4-yl)-2-oxo-2-(2-thiazolyl)ethyl]-4-oxo-2-(3-phenylpropionyl)octahydropyrrolo[1,2-a]pyrazine-6-carboxamide
CAS No. 219832-87-8
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator), Shire BioChem (Originator)
合成路线:The condensation of 1-(benzyloxycarbonyl)piperidin-4-one with N-(tert-butoxycarbonyl)-2-phosphonoglycine trimethyl ester (II) by means of DBU in dichloromethane gives 2-[1-(benzyloxycarbonyl)piperidin-4-ylidene]-N-(tert-butoxycarbonyl)glycine methyl ester (III),which is selectively deprotected and reduced by hydrogenation with H2 over Pd/C in methanol yielding N-(tert-butoxycarbonyl)-2-(4-piperidyl)glycine methyl ester (IV).The reaction of (IV) with N,N'-di(tert-butoxycarbonyl)pyrazole-1-carboxamidine (V) by means of DIEA in dichloromethane gives the protected piperidine-1-carboxamidine (VI),which is treated with LiOH in methanol/water to obtain (VII) with a free carboxy group.The reaction of (VII) with O,N-dimethylhydroxylamine affords the hydroxamic ester (VIII),which is condensed with thiazole (IX) by means of butyllithium in THF yielding the fully protected intermediate (X).The deprotection of (X) with HCl in dioxane gives (XI) with free amino and amidino groups.The conddensation of (XI) with chiral acid (XII) by means of BOP and DIEA in acetonitrile yields amide (XIII) as a diastereomeric mixture that is resolved by preparative reverse-phase HPLC.