BMS-250749

Chemical Name: 3,9-Difluoro-12-(4-deoxy-4-fluoro-beta-D-glucopyranosyl)-5,6,12,13-tetrahydroindolo[2,3- a]pyrrolo[3,4-c]carbazole-5,7-dione
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Maleimide (I) was brominated in the presence of benzoyl peroxide to give 3,4-dibromomaleimide (II).Alkylation of (II) with 4-(tert-butyl)benzyl bromide (III) in the presence of potassium carbonate afforded the N-(tert-butylbenzyl) derivative (IV).Coupling of the dibromomaleimide (IV) with the indolylmagnesium iodide resulting from 5-fluoroindole (V) and MeMgI furnished the bis-indolyl maleimide (VI).Oxidative cyclization of (VI) using dicyanodichlorobenzoquinone yielded the target indolopyrrolocarbazole system (VIII).Glycosylation of (VIII) with the protected fluoro glucose derivative (VIII) under Mitsunobu conditions afforded adduct (IX).The O-benzyl protecting groups were then removed by transfer hydrogenation with cyclohexene and Pd(OH)2 to give (X).The tert-butylbenzyl group was finally removed by basic hydrolysis followed by recyclization with fused ammonium acetate.