Rafabegron, TAK-677, AJ-9677, AD-9677

2-[[3-[(2R)-2-[[(2R)-2-(3-氯苯基)-2-羟基-乙基]氨基]丙基]-1H-吲哚-7-基]氧基]乙酸Chemical Name: 2-[3-[2(R)-[2-(3-Chlorophenyl)-2(R)-hydroxyethylamino]propyl]-1H-indol-7-yloxy]acetic acid
CAS No. 244081-42-3, 179819-89-7 (undefined isomer)
项目整合开发状态: Discontinued
项目研究机构: Dainippon Pharmaceutical (Originator), Takeda (Licensee)
合成路线:Alkylation of 7-hydroxyindole (I) with methyl chloroacetate (II) provided indolyl ether (III).Conjugate addition of 2-nitropropene (IV) to indole (III) in refluxing benzene,afforded the 3-(2-nitropropyl)indole (V),which was further reduced to the corresponding amine (VI) by catalytic hydrogenation over Raney nickel.Ring opening of the chiral epoxide (VII) with the racemic amine (VI) gave rise to a diastereomeric mixture of amino alcohols (VIII).After isolation of the desired (R,R)-isomer by column chromatography,basic hydrolysis of the methyl ester function yielded the title carboxylic acid.