【药物名称】TCV-309
化学结构式(Chemical Structure):
参考文献No.12958
标题:Pyridinium nitrate, its production and use
作者:Tsushima, S.; Takatani, M.; Nishikawa, K. (Takeda Chemical Industries, Ltd.)
来源:EP 0382380; JP 1990275876; US 4981860
合成路线图解说明:

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-).

参考文献No.215475
标题:TCV-309
作者:Mealy, N.; Prous, J.; Casta馿r, J.
来源:Drugs Fut 1993,18(8),721
合成路线图解说明:

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-).

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