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【结 构 式】 
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【分子编号】24397 【品名】5-amino-1,3,4-thiadiazole-2(3H)-thione 【CA登记号】2349-67-9 |
【 分 子 式 】C2H3N3S2 【 分 子 量 】133.19804 【元素组成】C 18.03% H 2.27% N 31.55% S 48.15% |
合成路线1
该中间体在本合成路线中的序号：(III)Pentafluorophenylalanine methyl ester (I) was treated with phosgene and pyridine to afford isocyanate (II), which was condensed with 5-aminothiadiazole-2-thione (III) to provide urea (IV). Then, displacement of the ester function of (IV) with 1-(2-pyridyl)piperazine (V) furnished the title amide.
| 【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525. |
| 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) | 24395 | methyl (2S)-2-amino-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C10H8F5NO2 | 详情 | 详情 | |
| (II) | 24396 | methyl (2S)-2-isocyanato-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C11H6F5NO3 | 详情 | 详情 | |
| (III) | 24397 | 5-amino-1,3,4-thiadiazole-2(3H)-thione | 2349-67-9 | C2H3N3S2 | 详情 | 详情 |
| (IV) | 24398 | methyl (2S)-3-(2,3,4,5,6-pentafluorophenyl)-2-([[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino)propanoate | C13H9F5N4O3S2 | 详情 | 详情 | |
| (V) | 24399 | 1-(2-pyridinyl)piperazine | 34803-66-2 | C9H13N3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Pentafluorophenylalanine methyl ester (I) was treated with phosgene and pyridine to afford isocyanate (II), which was condensed with 5-aminothiadiazole-2-thione (III) to provide urea (IV). Then, displacement of the ester function of (IV) with methylamine furnished the title amide.
| 【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525. |
| 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) | 24395 | methyl (2S)-2-amino-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C10H8F5NO2 | 详情 | 详情 | |
| (II) | 24396 | methyl (2S)-2-isocyanato-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C11H6F5NO3 | 详情 | 详情 | |
| (III) | 24397 | 5-amino-1,3,4-thiadiazole-2(3H)-thione | 2349-67-9 | C2H3N3S2 | 详情 | 详情 |
| (IV) | 24398 | methyl (2S)-3-(2,3,4,5,6-pentafluorophenyl)-2-([[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino)propanoate | C13H9F5N4O3S2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)The reaction of L-phenylalanine methyl ester (I) with phosgene and pyridine in dichloromethane gives the isocyanate (II) (1), which is condensed with 5-amino-1,3,4-thiadiazol-2(3H)-thione (III) in THF to yield the urea (IV). Finally, this compound is treated with methylamine in ethanol to affords the target compound.
| 【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525. |
| 【2】 Jacobsen, E.J.; Mitchell, M.A.; Schostarez, H.J.; Harper, D.E. (Pharmacia & Upjohn AB); Thiadiazolyl(thio)ureas useful as matrix metalloprotease inhibitors. EP 0900211; JP 2000509039; WO 9740031 . |
| 【3】 Mitchell, M.A.; Schostarez, H.J.; Harper, D.E.; Jacobsen, E.J. (Pharmacia Corp.); Thiadiazole derivs. useful for the treatment of diseases related to connective tissue degradation. US 5847148 . |
| 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) | 12324 | methyl (2R)-2-amino-3-phenylpropanoate | 21685-51-8 | C10H13NO2 | 详情 | 详情 |
| (II) | 38888 | methyl (2S)-2-isocyanato-3-phenylpropanoate | 40203-94-9 | C11H11NO3 | 详情 | 详情 |
| (III) | 24397 | 5-amino-1,3,4-thiadiazole-2(3H)-thione | 2349-67-9 | C2H3N3S2 | 详情 | 详情 |
| (IV) | 38889 | methyl (2S)-3-phenyl-2-([[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino)propanoate | C13H14N4O3S2 | 详情 | 详情 |