TCV-309

2-[3-[(2-溴-1-丙基吡啶-4-羰基)-苯基氨基]丙烷胺基]乙基 3,4-二氢-1H-异喹啉-2-羧酸镍trateChemical Name: 3-Bromo-5-[N-phenyl-N-[2-[2-(1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyloxy)ethylcarbamoyl]ethyl]carbamoyl]-1-propylpyridinium nitrate
CAS No. 131311-25-6
项目整合开发状态: Phase II
项目研究机构: Takeda (Originator)
合成路线:Protection of the amino group of 2-aminoethanol (I) with di-tert-butyldicarbonate,followed by reaction with phenylchlorocarbonate,gives 2-(tert-butoxycarbonylamino)ethylphenylcarbonate (II),which on reaction in refluxing 1,2,3,4-tetrahydroisoquinoline (III) yields 1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid 2-(tert-butoxycarbonylamino)ethyl ester (IV).Compound (IV) is deprotected with HCl in methanol to give 1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid 2-aminoethyl ester (V),which is coupled with 3-(N-tert-butoxycarbonyl-N-phenylamino)propanoic acid (VI) in the presence of dicyclohexylcarbodiimide to afford N-[2-(1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyloxy)ethyl]-3-(N'-tert-butoxycarbonyl-N'-phenylamino)propanamide (VII).Deprotection of (VII) with HCl in methanol gives N-[2-(1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyloxy)ethyl]-3-(phenylamino)propanamide (VIII),which is acylated with 5-bromonicotinoyl chloride hydrochloride (IX) in the presence of triethylamine to yield 3-bromo-5-[N-phenyl-N-[2-[2-(1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyloxy)ethylcarbamoyl]ethyl]carbamoyl]pyridine (X).Compound (X) is finally reacted with iodopropane and iodide anion exchanged by nitrate with IRA-410 (NO3-).