VB-19026

Chemical Name: N-[3-[3(S)-Benzyl-5-oxo-1,4-diazaspiro[5.5]undec-4-yl]-2(S)-hydroxypropyl]-N-(cyclopentylmethyl)-4-methoxybenzenesulfonamide
项目整合开发状态: Biological Testing
项目研究机构: Vertex (Originator)
合成路线:N-Cbz-L-Phenylalaninol (I) was converted to mesylate (II) on treatment with methanesulfonyl chloride and Et3N,and then treated with benzylamine (III) in the presence of NaI to give (IV).Subsequent deprotection of the Cbz group of (IV) with HBr in AcOH afforded diamine (V),which was treated with carbonyl diimidazole to produce the cyclic urea (VI).Finally,condensation with the epoxisulfonamide (VII) in the presence of NaH in DMF provided the target compound.

合成路线:Reductive alkylation of aminoester (I) with N-Cbz-L-phenylalaninal (II) using NaBH3CN and AcOH in DMF provided compound (III).Subsequent deprotection of the Cbz group of (III) with HBr in AcOH afforded the diamine salt (IV),which upon basification with diisopropylamine resulted in lactamization to produce piperazinone (V).The secondary amine of (V) was then protected by alkylation with benzyl bromide to give (VI),which was condensed with the epoxisulfonamide (VII) in the presence of NaH in DMF to furnish (VIII).Finally,hydrogenolysis of the N-benzyl group in the presence of Pd(OH)2 yielded the target compound.