UR-12947

Chemical Name: 3-[4-Isopropyl-2-[4-(4-piperidinyl)piperidin-1-yl]thiazol-5-ylcarboxamido]-2(S)-(phenylsulfonamido)propionic acid
项目整合开发状态: Preclinical
项目研究机构: Uriach (Originator)
合成路线:The selective monoprotection of 4-(4-piperidyl)piperidine (I) gives the carbamate (II),which is condensed with the isothiocyante (III) in chloroform to yield the N-(ethoxycarbonyl)carbothioamide (IV).Decarboxylation of (IV) by means of NaOH in ethanol affords the free thioamide (V),which is cyclized with 2-chloro-4-methyl-3-oxopentanoic acid ethyl ester (VI) by means of triethylamine in ethanol to provide the thiazole derivative (VII).Hydrolysis of theester group of (VII) with NaOH in ethanol gives the carboxylic acid (VIII),which is condensed with 3-amino-2(S)-(phenylsulfonamido)propionic acid methyl ester (IX),by means of DCC,HOBT and triethylamine in DMF yielding the protected target compound (X).Finally,this compound is hydrolyzed and deprotected by a treatment with HCl in ethanol.The intermediate 3-amino-2(S)-(phenylsulfonamido)propionic acid methyl ester (IX) has been obtained as follows: The reaction of L-asparagine (XI) with benzenesulfonyl chloride (XII) by means of NaOH in dioxane/water gives the sulfonated asparagine (XIII),which is submitted to Hofmann degradation with Br2 and NaOH in water and finally esterified with SOCl2 and methanol.