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【结 构 式】 
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【分子编号】33082 【品名】tert-butyl 2-[[(2-amino-5-sulfanyl-1,3-thiazol-4-yl)methyl]sulfanyl]ethylcarbamate 【CA登记号】 |
【 分 子 式 】C11H19N3O2S3 【 分 子 量 】321.48888 【元素组成】C 41.1% H 5.96% N 13.07% O 9.95% S 29.92% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of 1,3-dichloroacetone (I) with thiourea (II) provided 2-amino-4-(chloromethyl)thiazole (III). Further displacement of the chlorine atom of (III) with N-Boc-2-mercaptoethylamine (IV) gave thioether (V). Thiocyanation of the thiazole ring of (V) using thiocyanogen, generated from KSCN and Br2, provided (VI). Reductive cleavage of the thiocyanate group of (VI) with NaBH4 gave rise to the mercaptothiazole (VII), which was subsequently coupled with the chlorocephem (VIII) to yield adduct (IX). Incorporation of a N-Boc-alanine unit to (IX) to afford (XI) was then achieved by condensation with N-Boc-alanine pentafluorophenyl ester (X) in 1,2-dichloroethane. Finally, the protecting groups of (XI) were cleaved by treatment with trifluoroacetic acid in the presence of triethylsilane.
| 【1】 Glinka, T.; Price, M.; Halas, S.; Calkins,T.; Frith, R.; Nudelman, G.; Whitehead, C.; Cho, A.; Hecker, S.; Ludwikow, M.; Chamberland, S.; Crawford, J.; Lee, V.; Design, synthesis and in vitro antibacterial properties of novel 3-heteroarylthio cephems with anti-MRSA activity: Amino acid prodrug approach to solubility improvement. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F391. |
| 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) | 63907 | 1,3-dichloroacetone | C3H4Cl2O | 详情 | 详情 | |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 33078 | 4-(chloromethyl)-1,3-thiazol-2-amine; 4-(chloromethyl)-1,3-thiazol-2-ylamine | C4H5ClN2S | 详情 | 详情 | |
| (IV) | 33079 | tert-butyl 2-sulfanylethylcarbamate | C7H15NO2S | 详情 | 详情 | |
| (V) | 33080 | tert-butyl 2-[[(2-amino-1,3-thiazol-4-yl)methyl]sulfanyl]ethylcarbamate | C11H19N3O2S2 | 详情 | 详情 | |
| (VI) | 33081 | tert-butyl 2-([[2-amino-5-(cyanosulfanyl)-1,3-thiazol-4-yl]methyl]sulfanyl)ethylcarbamate | C12H18N4O2S3 | 详情 | 详情 | |
| (VII) | 33082 | tert-butyl 2-[[(2-amino-5-sulfanyl-1,3-thiazol-4-yl)methyl]sulfanyl]ethylcarbamate | C11H19N3O2S3 | 详情 | 详情 | |
| (VIII) | 33083 | benzyl 3-chloro-7-([2-[4-chloro-2-(tritylamino)-1,3-thiazol-5-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C57H43Cl2N5O5S2 | 详情 | 详情 | |
| (IX) | 33084 | benzyl 3-([2-amino-4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-1,3-thiazol-5-yl]sulfanyl)-7-([2-[4-chloro-2-(tritylamino)-1,3-thiazol-5-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C68H61ClN8O7S5 | 详情 | 详情 | |
| (X) | 33085 | 2,3,4,5,6-pentafluorophenyl (2S)-2-[(tert-butoxycarbonyl)amino]propanoate | C14H14F5NO4 | 详情 | 详情 | |
| (XI) | 33086 | benzyl 3-[[4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-2-([(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-1,3-thiazol-5-yl]sulfanyl]-7-([2-[4-chloro-2-(tritylamino)-1,3-thiazol-5-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; benzyl 3-[[4-[([2-[(tert-butoxycarbonyl)amino]ethyl]sulfanyl)methyl]-2-([(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-1,3-thiazol-5-yl]sulfanyl]-7-([2-[4-chloro-2-(tritylamino)-1,3-thiazol-5-yl]-2-[(trityloxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C76H74ClN9O10S5 | 详情 | 详情 |