【结 构 式】 |
【药物名称】 【化学名称】N-[2-(1H-Indol-3-yl)ethyl]-7,8-dihydroisoquinoline-6-carboxamide hydrochloride 【CA登记号】227199-46-4 (free base) 【 分 子 式 】C20H20ClN3O 【 分 子 量 】353.8549 |
【开发单位】Shire BioChem (Originator) 【药理作用】Anti-Cytomegalovirus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
Oxidation of 5-hydroxy-5,6,7,8-tetrahydroisoquinoline (I) using CrO3 in pyridine produced the corresponding ketone (II). Subsequent condensation of (II) with methyl cyanoformate (A) in the presence of lithium hexamethyldisilazide gave ketoester (III), which was reduced to hydroxyester (IV) by means of catalytic hydrogenation. Dehydration of (IV) to the unsaturated ester (V) was achieved by treatment with methanesulfonyl chloride and triethylamine, followed by basic elimination with DBU. Saponification of the ester group of (V) produced carboxylic acid (VI). After activation of (VI) as the mixed anhydride (VII) with isopropyl chloroformate (B), coupling with tryptamine (VIII) furnished the title amide, which was finally isolated as the hydrochloride salt.
【1】 May, S.; Chan, L.; Chen, Y.; Jin, H.; Hu, Z.; Bedard, J.; Stefanac, T.; Turcotte, N.; Design and evaluation of dihydroisoquinolines as potent and orally bioavailable human cytomegalovirus inhibitors. Bioorg Med Chem Lett 2000, 10, 13, 1477. |
【2】 Bedard, J.; Rando, R.; Falardeau, G.; Lavallee, J.-F. (BioChem Pharma Inc.); Antiviral cpds.. WO 9929318 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 18001 | methyl 2-nitriloacetate; carbonocyanic acid, methyl ester | 17640-15-2 | C3H3NO2 | 详情 | 详情 |
(B) | 26492 | 2-[(chlorocarbonyl)oxy]propane | 108-23-6 | C4H7ClO2 | 详情 | 详情 |
(I) | 40530 | 5,6,7,8-tetrahydro-5-isoquinolinol | C9H11NO | 详情 | 详情 | |
(II) | 40531 | 7,8-dihydro-5(6H)-isoquinolinone | C9H9NO | 详情 | 详情 | |
(III) | 40532 | methyl 5-hydroxy-7,8-dihydro-6-isoquinolinecarboxylate | C11H11NO3 | 详情 | 详情 | |
(IV) | 40533 | methyl 5-hydroxy-5,6,7,8-tetrahydro-6-isoquinolinecarboxylate | C11H13NO3 | 详情 | 详情 | |
(V) | 40534 | methyl 7,8-dihydro-6-isoquinolinecarboxylate | C11H11NO2 | 详情 | 详情 | |
(VI) | 40535 | 7,8-dihydro-6-isoquinolinecarboxylic acid | C10H9NO2 | 详情 | 详情 | |
(VII) | 40536 | C14H15NO4 | 详情 | 详情 | ||
(VIII) | 40537 | Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine | 61-54-1 | C10H12N2 | 详情 | 详情 |