T-1172

Chemical Name: N-[1-(2-Fluorophenyl)-6-methoxy-3(S)-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-9H-beta-carboline-3-carboxamide methanesulfonate; N-[1-(2-Fluorophenyl)-6-methoxy-3(S)-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-9H-pyrido[3,4-b]indole-3-carboxamide methanesulfonate
CAS No. 169200-57-1 ((+)-enantiomer), 169200-56-0 ((+)-enantiomer, free base), 154058-68-1 (undefined stereoch.), 154058-67-0 (undefined stereoch., free base)
项目整合开发状态: Preclinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:The isatin derivative (III) was prepared by acylation of diarylamine (I) with oxalyl chloride,followed by intramolecular cyclization of the intermediate (II) under Friedel-Crafts reaction conditions.Treatment of (III) with hydroxylamine led to formation of the oxime (IV),which was further reduced to amine (V) by catalytic hydrogenation over Pd/C.After protection of amine (V) as the benzyl carbamate (VI),alkylation with iodomethane in the presence of K2CO3 produced the 3-methyl oxindole (VII).Removal of the N-carbobenzoxy group of (VII) was achieved by catalytic hydrogenation over Pd/C to yield the deprotected amine,which was resolved by means of dibenzoyl-L-tartaric acid.The target (S)-amine (VIII) was finally acylated with beta-carboline-3-carbonyl chloride (IX) to furnish the title amide.