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【结 构 式】 
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【分子编号】30745 【品名】3-[[(2-amino-1,3-thiazol-4-yl)methyl]sulfanyl]propanenitrile 【CA登记号】76823-89-7 |
【 分 子 式 】C7H9N3S2 【 分 子 量 】199.30068 【元素组成】C 42.19% H 4.55% N 21.08% S 32.18% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction ot S-(2-aminothiazol-4-ylmethyl)isothiourea (I) with 3-chloropropionitrile (II) by means of NaOH in ethanol - water gives 3-(2-aminothiazol-4-ylmethylthio)propionitrile (III), which is condensed with benzoyl isothiocyanate (IV) in refluxing acetone to afford 3-[2-(3-benzoylthioureido)thiazol-4-ylmethylthio]propionitrile (V). The hydrolysis of (V) with K2CO3 in acetone - methanol - water yields 3-(2-thioureidothiazonl-4-ylmethylthio)propionitrile (VI), which by methylation with methyl iodide in refluxing ethanol is converted into 3-[2-(S-methylisothioureido)thiazol-4-ylmethylthio]propionitrile hydroiodide (VII). The reaction of (VII) with NH3 and NH4Cl in methanol at 90 C in a pressure vessel affords 3-(2-guanidinothiazol-4-ylmethylthio)propionitrile (VIII), which by partial alcoholysis with methanol by means of dry HCl in CHCl3 is converted into methyl 3-(2-guanidinothiazol-4-ylmethylthio)propionimidate (IX). Finally, this compound is treated with sulfamide in refluxing methanol.
| 【1】 Isomura, Y.; Ishii, Y.; Ito, N.; Takeda, M.; Yanagisawa, I.; Hirata, Y.; Tsukamoto, S. (Yamanouchi Pharmaceutical Co., Ltd.); Guanidinothiazole cpds., process for preparation and gastric inhibiting compsns. containing them. US 4283408 . |
| 【2】 Hirata Y.; et al. (Yamanouchi Pharmaceutical Co., Ltd.); Novel amidine derivative and its preparation. BE 0882071; DE 2951675; DE 3008056; FR 2450827; GB 2052478; GB 2055800; JP 55118476; NL 7909321; NL 8001361 . |
| 【3】 Blancafort, P.; Castaner, J.; Hillier, K.; Serradell, M.N.; Famotidine. Drugs Fut 1983, 8, 1, 14. |
| 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) | 30743 | 2-amino-4-([[amino(imino)methyl]sulfanyl]methyl)-1,3-thiazole | C5H8N4S2 | 详情 | 详情 | |
| (II) | 30744 | 3-chloropropanenitrile | 542-76-7 | C3H4ClN | 详情 | 详情 |
| (III) | 30745 | 3-[[(2-amino-1,3-thiazol-4-yl)methyl]sulfanyl]propanenitrile | 76823-89-7 | C7H9N3S2 | 详情 | 详情 |
| (IV) | 23530 | benzoyl isothiocyanate | 532-55-8 | C8H5NOS | 详情 | 详情 |
| (V) | 30746 | N-benzoyl-N'-(4-[[(2-cyanoethyl)sulfanyl]methyl]-1,3-thiazol-2-yl)thiourea | C15H14N4OS3 | 详情 | 详情 | |
| (VI) | 30747 | N-(4-[[(2-cyanoethyl)sulfanyl]methyl]-1,3-thiazol-2-yl)thiourea | C8H10N4S3 | 详情 | 详情 | |
| (VII) | 30748 | 4-[[(2-cyanoethyl)sulfanyl]methyl]-2-[[imino(methylsulfanyl)methyl]amino]-1,3-thiazole | C9H12N4S3 | 详情 | 详情 | |
| (VIII) | 30749 | N''-(4-[[(2-cyanoethyl)sulfanyl]methyl]-1,3-thiazol-2-yl)guanidine; 2-[4-(2-Cyanoethyl)methylthio]thioazolyl guanidine | 76823-93-3 | C8H11N5S2 | 详情 | 详情 |
| (IX) | 30750 | methyl 3-[([2-[(diaminomethylene)amino]-1,3-thiazol-4-yl]methyl)sulfanyl]propanimidoate | C9H15N5OS2 | 详情 | 详情 |