新产品编号:209333

Chemical Name: 2-(2-Amidino-1,2,3,4-tetrahydroisoquinolin-7-yloxy)-2-[4-(1-amidino-4-piperidinyloxy)phenyl]acetic acid dihydrochloride
CAS No. 188576-47-8
项目整合开发状态: Biological Testing
项目研究机构: Roche (Originator)
合成路线:The reaction of 7-hydroxy-1,2,3,4-tetrahydroisoquinoline (I) with di-tert-butyl dicarbonate and triethylamine in dichloromethane gives 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl ester (II),which is condensed with 2-(4-benzyloxyphenyl)-2-chloroacetic acid ethyl ester (III) (obtained by chlorination of 2-(4-benzyloxyphenyl)acetic acid ethyl ester (IV) with PCl5),by means of K2CO3 in refluxing acetonitrile yields the disubstituted acetate (V).The selective debenzylation of (V) with H2 over Pd/C in ethyl acetate affords the phenol (VI),which is alkylated with 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (VII) by means of diethyl azodicarboxylate (AZE) and triphenyl phosphine providing the protected intermediate (VIII).The deprotection of (VIII) with HCl in ethanol gives intermediate (IX) with two free NH groups,which is treated with pyrazole-1-carboxamidine (X) and diisopropylethylamine (DIEA) in DMF yielding the bis amidino derivative (XI),which is finally hydrolyzed with NaOH in ethanol/water.