ST-1455(free base)

Chemical Name: (?-7-Chloro-9-(4-methylpiperazin-1-yl)-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepine dihydrochloride
CAS No. 214270-71-0 (free base)
项目整合开发状态: Preclinical
项目研究机构: Sigma-Tau (Originator)
合成路线:Friedel-Crafts acetylation of 4-chlorothioanisole (I) gave acetophenone (II),which was then brominated to afford the corresponding bromoketone (III).Further reaction of (III) with hexamethylenetetramine,followed by acid hydrolysis yielded the aminoketone (IV).The Clauson-Kaas reaction of amine (IV) with 2,5-dimethoxytetrahydrofuran (V) in the presence of AcOH-AcONa provided pyrrole (VI),and then the thioether function of (VI) was oxidized to sulfoxide (VII) with sodium periodate.The subsequent Pummerer cyclization using trifluoroacetic anhydride produced an intermediate tricyclic sulfonium salt (VIII) that,upon losing a methyl group,yielded the pyrrolobenzothiazepine (IX).Reduction of the ketone function of (IX) to alcohol (X) with NaBH4,followed by treatment with PBr3,furnished bromide (XI).Finally,displacement of the bromide of (XI) at 130 C with N-methylpiperazine (XII) provided the title compound,which was isolated as the dihydrochloride salt on treating with methanolic HCl.