新产品编号:916487

Chemical Name: N-(2,5-Difluorobenzyl)-4-[4-[2-[2(S)-hydroxy-3-[4-hydroxy-3-(methylsulfonamido)phenoxy]propylamino]ethyl]phenylamino]piperidine-1-carboxamide
CAS No. 392630-57-8
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:The chiral epoxide (VIII) was prepared as follows.4-Hydroxy-3-nitroacetophenone (I) was protected as the silyl derivative (II) and then subjected to a Baeyer-Villiger rearrangement to afford the phenol acetate ester (III).Hydrogenation of the nitro group of (III) over Raney nickel provided aniline (IV),which was acylated by methanesulfonyl chloride producing sulfonamide (V).After protection of the sulfonamide NH of (V) with Boc2O,basic hydrolysis of the acetate ester furnished phenol (VI).Mitsunobu coupling between phenol (VI) and (R)-glycidol (VII) led to the glycidyl ether (VIII).

合成路线:4-Aminophenethylamine (IX) was selectively protected at the aliphatic amino group by means of Boc2O to afford (X).Reductive alkylation of aniline (X) with N-benzyl-4-piperidone (XI) in the presence of NaBH(OAc)3 furnished the secondary amine (XII).Subsequent N-benzyl group cleavage in (XI) by transfer hydrogenolysis gave rise to diamine (XIII),which was further converted to urea (XV) by coupling with isocyanate (XIV).The N-Boc group of (XV) was then cleaved by means of formic acid,yielding amine (XVI).The title compound was then obtained by condensation of amine (XVI) with epoxide (VIII),followed by removal of the N-Boc and silyl protecting groups.