新产品编号:2397239

Chemical Name: 4-[4-[3-[4(R)-Methyl-2,5-dioxo-3-phenylimidazolidin-1-yl]propoxy]phenylsulfonyl]tetrahydro-2H-pyran-4-carbohydroxamic acid
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Tetrahydropyran-4-carboxylic acid tert-butyl ester (I) is treated with 4-fluorophenyl disulfide (II) in the presence of LDA to produce sulfide (III),which is further oxidized to the corresponding sulfone (IV) utilizing m-chloroperbenzoic acid.Displacement of the aryl fluoride (IV) with the sodium alkoxide of 3-(dibenzylamino)-1-propanol (V) affords the amino ether (VI).Debenzylation of (VI) by hydrogenation in the presence of Pd(OH)2/C gives the primary amine (VII).This is coupled with N-Boc-D-alanine (VIII) employing EDC to provide amide (IX).Cyclization of (IX) in the presence of DMAP,NMM and Boc2O leads to the N-protected hydantoin (X).The N-Boc group of (X) is then selectively removed by HCl in dioxane to furnish (XI).

合成路线:N-Arylation of hydantoin (XI) with phenylboronic acid in the presence of cupric acetate gives rise to the N-phenyl hydantoin (XII).Subsequent hydrolysis of the tert-butyl ester with trifluoroacetic acid in CH2Cl2 affords acid (XIII).This is then coupled with O-(tetrahydropyranyl)-hydroxylamine,yielding the tetrahydropyranyl-protected hydroxamic acid (XIV).Finally,removal of the tetrahydropyranyl protecting group of (XIV) under acidic conditions provides the title compound.