W-3646

Chemical Name: 3-[3-[N-Isopropyl-N-(4-methoxyphenylsulfonyl)amino]phenyl]-3-(3-pyridyl)-2(E)-propenohydroxamic acid
项目整合开发状态: Preclinical
项目研究机构: Wakunaga (Originator)
合成路线:Nitration of 3-benzoylpyridine (I) with KNO3 in sulfuric acid yielded the meta-nitrobenzoyl derivative (II).Wadsworth-Emmons reaction of ketone (II) with triethyl phosphonoacetate produced the unsaturated ester (IIIa-b) as a mixture of geometric isomers.Nitro group reduction in (IIIa-b) employing Fe and HCl gave aniline (IVa-b),which was condensed with 4-methoxybenzenesulfonyl chloride (V) to afford sulfonamide (VIa-b).After conversion of the pyridine ring of (VIa-b) to the corresponding N-oxide (VIIa-b) with m-chloroperbenzoic acid,the sulfonamide N atom of (VIIa-b) was alkylated with isopropyl iodide and K2CO3 to produce (VIIIa-b).Reduction of the N-oxide of (VIIIa-b) by means of Fe and HOAc,followed by basic hydrolysis of the ethyl ester,furnished acid (IXa-b).This was then coupled with O-t-butyldimethylsilyl hydroxylamine to provide,after separation of the Z/E isomeric mixture,the desired hydroxamic acid.