TA-993

(-)-(2R,3R)-3-乙氧基-5-[2-(二甲氨基)乙基]-8-甲基-2-(4-甲基苯基)-2,3,4,5-四氢-1,5-苯并噻西平-4-一马来酸盐Chemical Name: (-)-(2R,3R)-3-Acetoxy-5-[2-(dimethylamino)ethyl]-8-methyl-2-(4-methylphenyl)-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one maleate
CAS No. 150591-06-3
项目整合开发状态: Phase II
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:The required 2-amino-5-methylthiophenol (III) was obtained by basic hydrolysis of the aminobenzothiazole (II),which was prepared from p-toluidine (I) and in situ generated thiocyanogen.Reaction of thiophenol (III) with the arylglycidic ester (IV) produced the racemic threo-amino ester (V).After basic hydrolysis of the ester group of (V),the resultant amino acid was resolved by means of D-(4-hydroxyphenyl)glycine methyl ester.The required amino acid enantiomer (VI) was then cyclized to lactam (VII) by heating in xylene with azeotropic removal of water.N-alkylation of benzothiazepinone (VII) with 2-(dimethylamino)ethyl chloride (VIII) provided (IX).The secondary alcohol of (IX) was esterified with acetic anhydride,and the resultant compound was finally isolated as the corresponding maleate salt.