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【结 构 式】 
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【分子编号】16603 【品名】ethyl 1,3-thiazole-5-carboxylate 【CA登记号】32955-22-9 |
【 分 子 式 】C6H7NO2S 【 分 子 量 】157.19312 【元素组成】C 45.85% H 4.49% N 8.91% O 20.36% S 20.4% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The thiazolyl carbonate (XI) has been synthesized as follows: The reaction of formamide (XIV) with P2S5 in ethyl ether gives thioformamide (XV), which is cyclized with 2-chloro-3-oxopropionic acid ethyl ester (XVI) [obtained by condensation of ethyl chloroacetate (XVII) with ethyl formate (XVIII) by means of t-BuOK in THF] yielding thiazol-5-carboxylic acid ethyl ester (XIX). The reduction of (XIX) with LiAlH4 in THF affords 5-thiazolylmethanol (XX), which is then esterified with 4-nitrophenyl chloroformate (XXI) by means of 4-methylmorpholine (MPH) in dichloromethane to give the desired product (XI).
| 【1】 Graul, A.; Castañer, J.; Ritonavir. Drugs Fut 1996, 21, 7, 700. |
| 【2】 Kempf, D.J.; Norbeck, D.W.; Sham, H.L.; Zhao, C.; Sowin, T.J.; Reno, D.S.; Haight, A.R.; Cooper, A.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds. EP 0674513; EP 0727419; JP 1996505844; JP 1997118679; JP 1998087639; WO 9414436 . |
| 【3】 Al-Razzak, L.; Marsh, K.C.; Manning, L.P.; Kaul, D. (Abbott Laboratories Inc.); Pharmaceutical compsns. containing HIV protease inhibitors. EP 0732923; US 5484801; WO 9520384 . |
| 【4】 Flentge, C.; Kempf, D.; Marsh, K.; et al.; Symmetry-based inhibitors of HIV protease with high oral bioavailability. 207th ACS Natl Meet (March 13-17, San Diego) 1994, Abst MEDI 35. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 16595 | 4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate | 144163-97-3 | C11H8N2O5S | 详情 | 详情 |
| (XIV) | 16598 | Formamide | 75-12-7 | CH3NO | 详情 | 详情 |
| (XV) | 16599 | Thioformamide | CH3NS | 详情 | 详情 | |
| (XVI) | 16600 | ethyl 2-chloro-3-oxopropanoate | C5H7ClO3 | 详情 | 详情 | |
| (XVII) | 16601 | ethyl chloroacetate; ethyl 2-chloroacetate | 105-39-5 | C4H7ClO2 | 详情 | 详情 |
| (XVIII) | 16602 | ethyl formate | 109-94-4 | C3H6O2 | 详情 | 详情 |
| (XIX) | 16603 | ethyl 1,3-thiazole-5-carboxylate | 32955-22-9 | C6H7NO2S | 详情 | 详情 |
| (XX) | 16604 | 1,3-thiazol-5-ylmethanol;5-thiazolylmethanol;Thiazole-5-methanol | 38585-74-9 | C4H5NOS | 详情 | 详情 |
| (XXI) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |