【结 构 式】 |
【药物名称】SX-5216, AC-5216 【化学名称】N-Benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide 【CA登记号】226954-04-7 【 分 子 式 】C23H23N5O2 【 分 子 量 】401.47206 |
【开发单位】Dainippon Pharmaceutical (Originator), Novartis (Licensee) 【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, GABA(A) BZ Site Receptor Agonists |
合成路线1
Pyrimidinone (III) was formed by condensation of benzamidine hydrochloride (I) with diethyl (ethoxymethylene)malonate (II). Subsequent reaction with glycinamide derivative (V) in the presence of p-tosyl chloride and Et3N afforded the aminopyrimidine (VI) (1). Alternatively, aminopyrimidine (VI) was prepared by chlorination of pyrimidinone (III) with POCl3, followed by displacement of the resulting chloropyrimidine (IV) with glycinamide (V) (2). Basic hydrolysis of the ethyl ester group of (VI) furnished pyrimidinecarboxylic acid (VII). This was then subjected to a Curtius rearrangement employing diphenyl phosphoryl azide (DPPA) to produce the 8-oxopurine system (VIII). Finally, N-alkylation of (VIII) with iodomethane gave rise to the title compound.
【1】 Masumoto, K.; et al.; SX-5216, highly potent and selective mitochondrial benzodiazepine receptor ligand as a potential anxiolytic agent. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 113. |
【2】 Matsumoto, K.; Kondo, K.; Furukawa, K.; Murata, T.; Oka, M. (Dainippon Pharmaceutical Co., Ltd.); 2-Aryl-8-oxodihydropurine derivs., process for producing the same, medicinal compsns. containing the same, and intermediates thereof. EP 1036794; WO 9928320 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 37052 | Benzamidine; benzenecarboximidamide | C7H8N2 | 详情 | 详情 | |
(II) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
(III) | 40809 | ethyl 6-oxo-2-phenyl-1,6-dihydro-5-pyrimidinecarboxylate | C13H12N2O3 | 详情 | 详情 | |
(IV) | 40810 | ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate | C13H11ClN2O2 | 详情 | 详情 | |
(V) | 40811 | 2-amino-N-benzyl-N-ethylacetamide | C11H16N2O | 详情 | 详情 | |
(VI) | 40812 | ethyl 4-([2-[benzyl(ethyl)amino]-2-oxoethyl]amino)-2-phenyl-5-pyrimidinecarboxylate | C24H26N4O3 | 详情 | 详情 | |
(VII) | 40813 | 4-([2-[benzyl(ethyl)amino]-2-oxoethyl]amino)-2-phenyl-5-pyrimidinecarboxylic acid | C22H22N4O3 | 详情 | 详情 | |
(VIII) | 40814 | N-benzyl-N-ethyl-2-(8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide | C22H21N5O2 | 详情 | 详情 |