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【结 构 式】 
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【药物名称】 【化学名称】N-[1(S)-(5-Methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethyl]-4-oxo-4-phenyl-2(E)-butenamide 【CA登记号】 【 分 子 式 】C19H16N2O4S 【 分 子 量 】368.41437 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs, Protease Inhibitors |
合成路线1
The cyclization of 2-amino-4-methylthiophene-3-carboxylic acid (I) with N-(tert-butoxycarbonyl)-L-alanine (II), by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF gives the protected thienooxazinone (III), which is deprotected with trifluoroacetic acid in dichloro methane yielding 2-(1(S)-aminoethyl)-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one (IV). Finally, this compound is acylated with 4-oxo-4-phenyl-2(E)-butenoic acid (VI) by means of DEC and diisopropylethylamine in DMF.
| 【1】 Jarvest, R.L.; Pinto, I.L.; Clarke, B.; et al.; Inhibition of human cytomegalovirus protease by enedione derivatives of thieno[2,3-d]oxazinones through a novel dual acylation/alkylation mechanism. Bioorg Med Chem Lett 1999, 9, 3, 449. |
| 【2】 Jarvest, R.L.; Jennings, L.J.A.; Pinto, I.L. (SmithKline Beecham plc); Thienoxazinone derivs. useful as antiviral agents. WO 9727200 . |
| 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) | 28658 | 2-amino-4-methyl-3-thiophenecarboxylic acid | C6H7NO2S | 详情 | 详情 | |
| (II) | 26450 | Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid | 15761-38-3 | C8H15NO4 | 详情 | 详情 |
| (III) | 28659 | tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate | C14H18N2O4S | 详情 | 详情 | |
| (IV) | 28660 | 2-[(1S)-1-aminoethyl]-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one | C9H10N2O2S | 详情 | 详情 | |
| (V) | 28661 | (E)-4-oxo-4-phenyl-2-butenoic acid | 583-06-2 | C10H8O3 | 详情 | 详情 |