【结 构 式】 |
【分子编号】25099 【品名】methyl (2S)-2-[(butoxycarbonyl)amino]-3-[([3-[(4-cyanobenzyl)oxy]-5-isoxazolyl]carbonyl)amino]propanoate 【CA登记号】 |
【 分 子 式 】C21H24N4O7 【 分 子 量 】444.44432 【元素组成】C 56.75% H 5.44% N 12.61% O 25.2% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The esterification of (S)-3-amino-2-(benzyloxycarbonylamino)propionic acid (I) with methanol/HCl gives the expected methyl ester (II), which is protected with di-tert-butyl dicarbonate and triethylamine in chloroform to the fully protected compound (III). The debenzylation of (III) by treatment with formic acid over Pd/C in methanol yields the 2-amino compound (IV), which is acylated with butyl chloroformate and NaHCO3 in THF affording 2(S)-(n-butoxycarbonylamino)-3-(tert-butoxycarbonylamino)propionic acid methyl ester (V).The selctive deacylation of (V) with trifluoroacetic acid in dichloromethane affords the 3-amino-2(S)-(n-butoxycarbonylamino)propionic ester (VI), which is acylated with 3-(4-cyanobenzyloxy)isoxazole-5-carboxylic acid (VII) by means of BOP or TBTU and triethylamine or DIEA in DMF giving the cyanobenzyl derivative (VIII). Finally, this compound treated first with HCl in methanol, and then with NH3 in the same solvent to provide the target compound.
【1】 Xue, C.-B.; Roderick, J.; Mousa, S.; Olson, R.E.; DeGrado, W.F.; Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists. Bioorg Med Chem Lett 1998, 8, 24, 3499. |
【2】 Degrado, W.F.; Xue, C.-B. (DuPont Pharmaceuticals Co.); Cpds. containing basic and acidic termini useful as fibrinogen receptor antagonists. US 5563158; WO 9518111 . |
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) | 18008 | (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid | 35761-26-3 | C11H14N2O4 | 详情 | 详情 |
(II) | 25093 | methyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate | C12H16N2O4 | 详情 | 详情 | |
(III) | 25094 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[(tert-butoxycarbonyl)amino]propanoate | C17H24N2O6 | 详情 | 详情 | |
(IV) | 25095 | methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate | C9H18N2O4 | 详情 | 详情 | |
(V) | 25096 | methyl (2S)-3-[(tert-butoxycarbonyl)amino]-2-[(butoxycarbonyl)amino]propanoate | C14H26N2O6 | 详情 | 详情 | |
(VI) | 25097 | methyl (2S)-3-amino-2-[(butoxycarbonyl)amino]propanoate | C9H18N2O4 | 详情 | 详情 | |
(VII) | 25098 | 3-[(4-cyanobenzyl)oxy]-5-isoxazolecarboxylic acid | C12H8N2O4 | 详情 | 详情 | |
(VIII) | 25099 | methyl (2S)-2-[(butoxycarbonyl)amino]-3-[([3-[(4-cyanobenzyl)oxy]-5-isoxazolyl]carbonyl)amino]propanoate | C21H24N4O7 | 详情 | 详情 | |
(X) | 25100 | methyl (2S)-3-([[3-([4-[amino(imino)methyl]benzyl]oxy)-5-isoxazolyl]carbonyl]amino)-2-[(butoxycarbonyl)amino]propanoate | C21H27N5O7 | 详情 | 详情 |