Hh-Ag 1.2

Chemical Name: 3-Chloro-N-(4'-cyano-6-methoxybiphenyl-3-ylmethyl)-N-[4-(methylamino)cyclohexyl]-1-benzothiophene-2-carboxamide
CAS No. 364590-54-5, 364590-91-0 (hydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Curis (Originator), Elan (Codevelopment)
合成路线:This compound can be obtained by two related ways:1) The hydrogenation of 4-(diisopropylamino)-2-phenyl-2-(2-pyridyl)butyramide (I) with H2 over PtO2 in acidic water gives the corresponding piperidine derivative (II),which is acetylated with acetic anhydride to the acetylpiperidine (III).Finally,this compound is cyclized by means of KOH in DMSO.2) The cyclization of piperidine derivative (II) whith dimethylacetamide dimethyl ketal (IV) at 80 C also yields the final product.

合成路线:1,4-Diaminocyclohexane (I) is converted into the mono-carbamate (II) employing di-tert-butyl dicarbonate in cold THF.Subsequent reduction of carbamate (II) by means of LiAlH4 leads to the N-methyl amine (III).After blocking the primary amino group of (III) as the corresponding benzaldimine (IV),treatment with di-tert-butyl dicarbonate gives rise to the mono-protected diamine (V).(1,2)

合成路线:Suzuki coupling between 2-methoxy-5-formylphenylboronic acid (VI) and 4-bromobenzonitrile (VII) affords the biphenyl aldehyde (VIII).This is then reductively condensed with amine (V) in the presence of NaBH(OAc)3 to furnish (IX).Acylation of amine (IX) with 3-chlorobenzo[b]thiophene-2-carbonyl chloride (X) leads to amide (XI).The N-Boc protecting group of (XI) is finally removed with ethanolic HCl to provide the title compound.(1,2)