化学合成。
化学合成
合成路线 1(1. 合成:16269-66-2)
产率:99%
合成条件:With oxalyl dichloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 2.50 h; Reflux
实验步骤:制备实施例3-3 4-氯 - 噻吩并[3,2-d]嘧啶的合成将二甲基甲酰胺(15.4ml,197.13mmol)加入到150ml二氯乙烷中,同时将温度降至0℃,加入草酰氯( 缓慢加入25毫升,295.70毫摩尔)。 当开始形成白色凝胶类型时,加入3H-噻吩并[3,2-d]嘧啶-4-酮(15g,98.57mmol)。 在反应混合物反射2.5小时后,将温度降至室温。 加入水后,用二氯甲烷(3×300ml)萃取反应混合物并用无水硫酸镁干燥。 真空浓缩后,用200ml己烷研磨,得到标题化合物(16.7g,99%),为深棕色固体。 1H NMR(400MHz,DMSO-d6); δ9.06(s,1H),8.61(d,J = 5.2Hz,1H),7.78(d,J = 5.2Hz,1H); LC-MS 173.2(MH +)
参考文献:
- [1] Patent: US2013/72482, 2013, A1. Location in patent: Paragraph 0211; 0216; 0217 [2] Patent: WO2005/51304, 2005, A2. Location in patent: Page/Page column 67-68 [3] Patent: WO2005/51304, 2005, A2. Location in patent: Page/Page column 67-68 [4] Patent: WO2006/10264, 2006, A1. Location in patent: Page/Page column 51; 67-68 [5] MedChemComm, 2015, vol. 6, # 2, p. 339 - 346 [6] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537 [7] Journal of Medicinal Chemistry, 1998, vol. 41, # 21, p. 4021 - 4035 [8] Bulletin de la Societe Chimique de France, 1970, p. 3630 - 3636 [9] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 1, p. 21 - 24 [10] Heterocyclic Communications, 2007, vol. 13, # 1, p. 33 - 34 [11] Bulletin de la Societe Chimique de France, 1970, p. 3630 - 3636 [12] Patent: US2003/225111, 2003, A1. Location in patent: Page 50, 51 [13] Patent: WO2009/7421, 2009, A1. Location in patent: Page/Page column 31; 34 [14] Patent: WO2009/7422, 2009, A1. Location in patent: Page/Page column 32; 35 [15] Heterocycles, 2008, vol. 75, # 12, p. 3091 - 3097 [16] Patent: US6806274, 2004, B1. Location in patent: Page/Page column 86 [17] Patent: WO2013/119895, 2013, A1. Location in patent: Page/Page column 76 [18] Heterocyclic Communications, 2017, vol. 23, # 4, p. 281 - 285 [19] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 1, p. 245 - 256