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【结 构 式】 
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【分子编号】69444 【品名】potassium 2-ethoxy-2-oxoacetate;potassium ethyl oxalate;Oxalic acid 1-ethyl 2-potassium salt 【CA登记号】1906-57-6 |
【 分 子 式 】C4H6KO4 【 分 子 量 】157.188 【元素组成】C 53.56% H 3.85% K 24.87% O 40.71% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)Aminocyclohexanecarboxylic acid ethyl ester (IV) and some synthetic precursors are prepared as follows. Acylation of 2-amino-5-chloropyridine (XXVII) with either potassium ethyl oxalate (XXVIII) by means of EDC and HOBt in DMF or with methyl oxalyl chloride (XXIX) in the presence of NaHCO3 in THF or CH2Cl2 or Et3N in CH2Cl2 provides the corresponding N-(5-chloro-2-pyridyl)-oxamic acid esters (XXI) and (XXX), respectively. The lithium oxamate (VI) has been prepared by hydrolysis of the methyl ester (XXX) with LiOH in aqueous THF . Coupling of the ehtyl pyridyloxamate (XXI) with the monoprotected diamine (XV) (previously derivatized as the corresponding malate or oxalate salt) in the presence of Et3N in acetonitrile at 65-70 ℃ yields oxamide (XXXI), which is finally deprotected to give intermediate (IV) by removing the N-Boc-protecting group by means of methanesulfonic acid in acetonitrile .
| 【1】 Ohta, T., Komoyira, S., Yoshimo, T. et al. (Daiichi Sankyo Co., Ltd.).Diamine derivatives. CA 2451605, CA 2456841, EP 1405852, EP 1415992, JP 2008143905, US 2005020645, US 2005119486, US 2005245565, US 2008015215, US 2009270446, US 7342014, US 7365205, WO 2003000657, WO 2003000680, WO 2003016302. |
| 【2】 Ohta, T., Komoriya, S., Yoshino, T. et al. (Daiichi Sankyo Co., Ltd.). Diamine derivatives. CA 2511493, EP 1577301, JP 2007070369, JP 2008138011, US 2006252837, US 2009281074, US 7576135, WO 2004058715. |
| 【3】 Schwartz, H.M., Wu, W.-S., Marr, P.W., Jones, J.B. Predicting the enantiomeric selectivity of chymotrypsin. Homologous series of ester substances. J Am Chem Soc 1978, 100(16): 5199-203. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 69423 | (1S,2R,4S)-ethyl 3-amino-4-(2-((5-chloropyridin-2-yl)amino)-2-oxoacetamido)cyclohexanecarboxylate | C16H21ClN4O4 | 详情 | 详情 | |
| (VI) | 69425 | N-(5-chloro-2-pyridyl)oxamic acid lithium salt;lithium 2-((5-chloropyridin-2-yl)amino)-2-oxoacetate | C7H4ClLiN2O3 | 详情 | 详情 | |
| (XV) | 69432 | (1R,3R,4S)-ethyl 4-amino-3-((tert-butoxycarbonyl)amino)cyclohexanecarboxylate | C14H26N2O4 | 详情 | 详情 | |
| (XXI) | 69438 | ethyl N-(5-chloro-2-pyridyl)oxamate;ethyl 2-((5-chloropyridin-2-yl)amino)-2-oxoacetate | C9H9ClN2O3 | 详情 | 详情 | |
| (XXVII) | 18559 | 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine | 1072-98-6 | C5H5ClN2 | 详情 | 详情 |
| (XXVIII) | 69444 | potassium 2-ethoxy-2-oxoacetate;potassium ethyl oxalate;Oxalic acid 1-ethyl 2-potassium salt | 1906-57-6 | C4H6KO4 | 详情 | 详情 |
| (XXIX) | 26971 | 2-methoxy-2-oxoacetyl chloride | 5781-53-3 | C3H3ClO3 | 详情 | 详情 |
| (XXX) | 69446 | methyl 2-((5-chloropyridin-2-yl)amino)-2-oxoacetate | C8H7ClN2O3 | 详情 | 详情 | |
| (XXXI) | 69445 | (1R,3S,4R)-ethyl 3-((tert-butoxycarbonyl)amino)-4-(2-((5-chloropyridin-2-yl)amino)-2-oxoacetamido)cyclohexanecarboxylate | C21H29ClN4O6 | 详情 | 详情 |