SB-656104(free base), SB-656104-A

Chemical Name: 6-[2(R)-[2-[4-(4-Chlorophenoxy)piperidin-1-yl]ethyl]pyrrolidin-1-ylsulfonyl]-1H-indole hydrochloride
CAS No. 446020-51-5 (free base)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Oxidation of N-Boc-D-prolinol (I) with pyridinium dichromate affords aldehyde (II).This is subjected to Wittig condensation with methylene triphenylphosphorane to furnish N-Boc-2-vinylpyrrolidine (III).Hydroboration of (III) with 9-borabicyclononane,followed by oxidative work-up,leads to the primary alcohol (IV).Subsequent acidic Boc group cleavage in (IV) provides 2-pyrrolidinyl ethanol (V).Acylation of amine (V) with 4-methyl-3-nitrobenzenesulfonyl chloride (VI) gives sulfonamide (VII).The hydroxyl group of (VII) is further protected with methoxymethyl chloride,producing the methoxymethyl ether (VIII).Conversion of the ortho-nitrotoluene system (VIII) into indole (X) is then accomplished according to the Leimgruber-Batcho procedure,by condensation of (VIII) with dimethylformamide dimethylacetal,followed by reduction of the resultant nitro enamine (IX) with hydrazine in the presence of Raney nickel.Protection of the indole N of (X) with benzenesulfonyl chloride and NaH affords sulfonamide (XI).After acidic hydrolysis of the methoxymethyl protecting group of (XI),the N-phenylsulfonyl group is removed under alkaline conditions to yield indole (XII)

合成路线:Conversion of alcohol (XII) into alkyl bromide (XIII) is carried out by treatment with carbon tetrabromide and triphenylphosphine.Then condensation of bromide (XIII) with 4-(4-chlorophenoxy)piperidine (XIV) in the presence of NaI and NaHCO3 produces the title compound