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【结 构 式】 
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【药物名称】Oxmetidine Hydrochloride, SK&F-92994-J2(mesylate), SK&F-92994(free base), SK&F-92994-A2 【化学名称】5-(1,3-Benzodioxol-5-ylmethyl)-2-[[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]amino]-4-(1H)-pyrimidinone dihydrochloride 【CA登记号】63204-23-9, 72830-39-8 (free base), 84455-52-7 (mesylate) 【 分 子 式 】C19H23Cl2N5O3S 【 分 子 量 】472.39686 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiulcer Drugs, GASTROINTESTINAL DRUGS, Histamine H2 Receptor Antagonists |
合成路线1
The cyclization of ethyl 2-formyl-3-(3,4-methylenedioxyphenyl)propionate (I) with nitroguanidine (II) by means of sodium methoxide in refluxing methanol gives 2-nitroamino-5-(3,4-methylenedioxybenzyl)-4-pyrimidone (III), which is then condensed with 2-(5-methyl-4-imidazolylmethylthio)ethylamine (IV) in refluxing ethanol.
| 【1】 Brown, T.H. (SmithKline Beecham plc); Process for preparing 2-aminopyrimidones, intermediate 2-nitroaminopyrimidones and a process for their preparation. EP 0004793 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Oxmetidine hydrochloride. Drugs Fut 1982, 7, 10, 749. |
| 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) | 37081 | ethyl 3-(1,3-benzodioxol-5-yl)-2-formylpropanoate | C13H14O5 | 详情 | 详情 | |
| (II) | 15496 | nitroguanidine | 556-88-7 | CH4N4O2 | 详情 | 详情 |
| (III) | 37082 | 5-(1,3-Benzodioxol-5-ylmethyl)-2-(nitroamino)-1H-pyrimidin-4-one | 72716-71-3 | C12H10N4O5 | 详情 | 详情 |
| (IV) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 |
合成路线2
The cyclization of ethyl 3-(3,4-ethylenedioxyphenyl)propionate (V), ethyl formate (VI) and thiourea (VII) by means of Na in ether and ethanol gives 5-(3,4-methylenedioxyphenyl)-2-thiouracil (VIII), which by reaction with methyl iodide and NaOH in ethanol-water is converted into 5-(3,4-methylenedioxybenzyl)-2-methylthio-4-pyrimidone (IX). Finally, this compound is condensed with (IV) by heating at 150 C.
| 【1】 Brown, T.H.; DE 2660563 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Oxmetidine hydrochloride. Drugs Fut 1982, 7, 10, 749. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 | |
| (V) | 37083 | ethyl 3-(1,3-benzodioxol-5-yl)propanoate | C12H14O4 | 详情 | 详情 | |
| (VII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VIII) | 37084 | 5-(1,3-benzodioxol-5-ylmethyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H10N2O3S | 详情 | 详情 | |
| (IX) | 37085 | 5-(1,3-benzodioxol-5-ylmethyl)-2-(methylsulfanyl)-4(1H)-pyrimidinone | C13H12N2O3S | 详情 | 详情 |