新产品编号:70117

Chemical Name: N-[5-(N-Hydroxyacetamido)pentyl]-N-hydroxy-2-(3-hydroxypyridin-2-yl)-4,5-dihydrothiazole-4(S)-carboxamide
CAS No. 155880-00-5
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator), University of Florida (Originator)
合成路线:The reaction of 1,5-dichloropentane (I) with N-(benzyloxy)carbamic tert-butyl ester (II) by means of NaH in DMF gives N-(benzyloxy)-N-(5-chloropentyl)carbamic acid tert-butyl ester (III),which is treated with TFA in dichloromethane to yield the O-(benzyloxy)hydroxylamine (IV).The acylation of (IV) with AcCl and NaOH in dichloromethane affords the acetamide (V),which is condensed with (II) by means of NaH in DMF giving the acetamidopentyl carbamate (VI),which is debenzylated with H2 over Pd/C in methanol providing the dihydroxy compound (VII).The treatment of (VII) with TFA in dichloromethane gives the free hydroxylamine derivative (VIII),which is finally condensed with the thiazolinecarboxylic acid (IX) by means of BOP and DIEA in DMF to furnish the target compound.Alternatively the condensation of intermediate N-(benzyloxy)-N-(5-chloropentyl) carbamic acid tert-butyl ester (III) with N-(benzyloxy)acetamide (XI) by means of NaH in DMF gives directly the previously described acetamidopentyl carbamate (VI).The intermediate the thiazolinecarboxylic acid (IX) has been obtained by cyclization of D-cysteine (XI) with 3-hydroxypyridine-2-carbonitrile (XII) by means of NaOH in water.