化学合成。
医药中间体
合成路线 1（1. 合成：40296-46-6）
产率：90%
合成条件：for 2 h; Reflux
实验步骤：将4,6-二羟基烟酸乙酯（60g，0.328mol）缓慢加入到POCl 3（500mL）中，然后加热回流2小时。 减压蒸馏所得混合物以除去过量的POCl 3。 将残余物倒入冰水中并搅拌30分钟，然后用EtOAc（3x）萃取。 合并的萃取液用盐水洗涤，干燥（MgSO 4）并真空浓缩，得到4,6-二氯烟酸乙酯（65g，90％，收率）。 1H NMR（300MHz，DMSO-d6）：δ8.80（s，1H），7.95（s，1H），4.34（q，J = 6.9Hz，2H），1.31（t，J = 6.9Hz，3H）; MS（ESI）m / z：220.1 [M + H] +。
参考文献：
- [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 7, p. 1487 - 1495 [2] European Journal of Organic Chemistry, 2014, vol. 2014, # 7, p. 1487 - 1495 [3] European Journal of Medicinal Chemistry, 2016, vol. 119, p. 17 - 33 [4] Patent: US8461179, 2013, B1. Location in patent: Page/Page column 66 [5] Patent: WO2013/184119, 2013, A1. Location in patent: Paragraph 0204 [6] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 3, p. 403 - 427 [7] Patent: WO2013/91011, 2013, A1. Location in patent: Page/Page column 66; 67 [8] European Journal of Medicinal Chemistry, 2014, vol. 86, p. 31 - 38 [9] Patent: US2005/49419, 2005, A1. Location in patent: Page/Page column 24 [10] Tetrahedron Letters, 2011, vol. 52, # 4, p. 512 - 514 [11] Antimicrobial Agents and Chemotherapy, 2016, vol. 60, # 8, p. 4442 - 4452 [12] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 7, p. 2355 - 2361 [13] Patent: WO2015/38417, 2015, A1. Location in patent: Page/Page column 76 [14] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690 [15] Journal of Medicinal Chemistry, 2007, vol. 50, # 21, p. 5090 - 5102 [16] Patent: US2004/142930, 2004, A1 [17] Patent: US2005/54701, 2005, A1 [18] Patent: WO2008/51757, 2008, A1. Location in patent: Page/Page column 31-32 [19] Patent: WO2005/34869, 2005, A2. Location in patent: Page/Page column 39-40 [20] Patent: US2007/60577, 2007, A1. Location in patent: Page/Page column 30; 43 [21] Patent: EP1847535, 2007, A1. Location in patent: Page/Page column 122 [22] Patent: WO2011/97526, 2011, A1. Location in patent: Page/Page column 30 [23] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 21, p. 6348 - 6352 [24] Patent: WO2014/52365, 2014, A1. Location in patent: Page/Page column 165-166 [25] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 52 - 62 [26] Patent: WO2007/136465, 2007, A2. Location in patent: Page/Page column 33 [27] Patent: WO2009/105712, 2009, A1. Location in patent: Page/Page column 35-36 [28] Patent: WO2005/34869, 2005, A2. Location in patent: Page/Page column 39-40
