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【结 构 式】

【分子编号】15625

【品名】1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid

【CA登记号】

【 分 子 式 】C8H11N3O4

【 分 子 量 】213.19316

【元素组成】C 45.07% H 5.2% N 19.71% O 30.02%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester (I) with hot dimethyl sulfate gives 1-methyl-3-propylpyrazole-5-carboxylic acid ethyl ester (II), which is hydrolyzed with aqueous NaOH to the corresponding free acid (III). The nitration of (III) with oleum/fuming nitric acid yields the 4-nitro derivative (IV), which is treated first with refluxing SOCl2 and then with NH4OH to afford the corresponding carboxamide (V). The reduction of the nitro group of (V) with SnCl2 dihydrate in refluxing ethanol gives 4-amino-1-methyl-3-propylpyrazole-5-carboxamide (VI), which is acylated with 2-ethoxybenzoyl chloride (VII) by means of triethylamine in dichloromethane yielding 4-(2-ethoxybenzamido)-1-methyl-3-propylpyrazole-5-carboxamide (VIII). The cyclization of (VIII) by means of NaOH and H2O2 in refluxing ethanol affords 5-(2-ethoxyphenyl)-1-methyl-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-7-one (IX), which is sulfonated with chlorosulfonic acid affording the chlorosulfonyl derivative (X). Finally, this compound is condensed with 1-methylpiperazine in ethanol at room temperature.

1 Martel, A.M.; Graul, A.; Rabasseda, X.; Castaner, R.M.; Sildenafil. Drugs Fut 1997, 22, 2, 138.
2 Terrett, N.K.; Bell, A.S.; Brown, D.; Ellis, P.; Sildenafil (Viagra(TM)), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett 1996, 6, 15, 1819-24.
3 Bell, A.S.; Brown, D.; Terrett, N.K. (Pfizer Inc.); Pyrazolopyrimidinone antianginal agents. EP 0463756; JP 1994041133; US 5250534; US 5346901 .
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) 15622 ethyl 3-propyl-1H-pyrazole-5-carboxylate C9H14N2O2 详情 详情
(II) 15623 ethyl 1-methyl-3-propyl-1H-pyrazole-5-carboxylate C10H16N2O2 详情 详情
(III) 15624 1-methyl-3-propyl-1H-pyrazole-5-carboxylic acid C8H12N2O2 详情 详情
(IV) 15625 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid C8H11N3O4 详情 详情
(V) 15626 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxamide; 4-Nitro-1-methyl-3-propyl-5-pyrazolecarboxamide 139756-01-8 C8H12N4O3 详情 详情
(VI) 15627 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide; 4-amino-1-methyl-3-propyl-5-pyrazolecarboxamide 139756-02-8 C8H14N4O 详情 详情
(VII) 15628 2-ethoxybenzoyl chloride 42926-52-3 C9H9ClO2 详情 详情
(VIII) 15629 4-[(2-ethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-carboxamide C17H22N4O3 详情 详情
(IX) 15630 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one; 5-(2-ethoxyphenyl)-1,6-dihydro-1-methyl-3-propyl-7H-pyrazolo[4,3-d]pyrimidin-7-one 139756-21-1 C17H20N4O2 详情 详情
(X) 15631 4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonyl chloride C17H19ClN4O4S 详情 详情
(XI) 10061 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine 109-01-3 C5H12N2 详情 详情
Extended Information