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【结 构 式】 
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【药物名称】Oxipurinol, Oxypurinol, NSC-76239, Oxyprim 【化学名称】1H-Pyrazolo[3,4-d]pyrimidine-4,6-diol 【CA登记号】2465-59-0 【 分 子 式 】C5H4N4O2 【 分 子 量 】152.11323 |
【开发单位】Cardiome (Proprietary), Cardiome (Orphan Drug), Ilex Oncology (Orphan Drug) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, METABOLIC DRUGS, Treatment of Disorders of Purine and Pyrimidine Metabolism, Treatment of Gout, Uricosurics, Xanthine Oxidase Inhibitors |
合成路线1
Cyanoacetic acid (I) is condensed with urethane (II) in hot Ac2O to afford N ethoxycarbonyl-cyanoacetamide (III). Subsequent reaction of (III) with triethyl orthoformate yields alpha-cyano-beta-ethoxy-N-ethoxycarbonyl-acrylamide (IV). The ethoxy group of (IV) is then displaced with hydrazine hydrate in EtOH to produce the hydrazino acrylamide (V). Finally, thermal cyclization of (V) gives rise to the title pyrazolopyrimidine (1, 2).
| 【1】 Hildick, B.G.; Shaw, G.; Purines, pyrimidines, and imidazoles. Part XXXVII. Some new syntheses of pyrazolo[3,4-d]pyrimidines, including allopurinol. J Chem Soc 1971, 9, 1610. |
| 【2】 Shaw, G.; Baildon, S.; Lees, P. Sr.; Process for the preparation of biologically active cpds. as well as novel cpds.. DE 1814082 . |
| 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) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (II) | 24199 | Ethyl carbamate; Urethane | 51-79-6 | C3H7NO2 | 详情 | 详情 |
| (III) | 48249 | ethyl 2-cyanoacetylcarbamate | C6H8N2O3 | 详情 | 详情 | |
| (IV) | 63576 | ethyl (E)-2-cyano-3-ethoxy-2-propenoylcarbamate | C9H12N2O4 | 详情 | 详情 | |
| (V) | 63577 | ethyl (E)-2-cyano-3-hydrazino-2-propenoylcarbamate | C7H10N4O3 | 详情 | 详情 |
合成路线2
In an alternative method, chlorination of pyrazole-3,4-dicarboxylic acid (I) with SOCl2 produces acid chloride (II), which is further converted into diamide (III) upon treatment with ammonia. Subsequent Hofmann rearrangement of amide (III) in the presence of sodium hypochlorite leads to the target pyrazolopyrimidine compound (3, 4).
| 【1】 Hitchings, G.H.; Falco, E.A. (GlaxoSmithKline Inc.); Treatment of hyperuricemia in humans. GB 0798646; US 3624205 . |
| 【2】 Hitchings, G.H.; Faco, E.A. (GlaxoSmithKline Inc.); Pyrazolo-(3,4-d) pyrimidines. US 3474098 . |