AT-1459

Chemical Name: 4-[1-[2-[2(S)-[2-(6-Amidino-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidin-1-yl]-2-oxoethyl]-2-oxohexahydro-1H-azepin-3(S)-ylamino]butyric acid
CAS No. 294658-50-7
项目整合开发状态: Preclinical
项目研究机构: C & C Research (Originator), Chugai (Codevelopment)
合成路线:The reaction of perhydroazepinone (I) with ethyl 2-bromoacetate (II) by means of LiHMDS in THF,followed by hydrolysis with KOH in methanol/water,gives the perhydroazepinylacetic acid (III),which is condensed with the pyrrolidine derivative (IV) by means of HOBt,WSCl and DIEA in dichloromethane to yield the adduct (V).The cleavage of the carbamate group of (V) with TFA in dichloromethane affords the 3-aminoperhydroazepinone (VI),which is condensed with ethyl 4-bromobutyrate (VII) by means of DIEA in acetonitrile to provide the 4-aminobutyrate derivative (VIII).The reaction of the cyano group of (VIII) with HCl in ethanol,followed by amonolysis with NH3 in the same solvent,gives the carboxamidine derivative (IX),which is hydrolyzed with KOH in ethanol/water to yield the target butyric acid derivative.