- 2-氯-4-(4-吗啉基)噻吩并[3,2-D]嘧啶为嘧啶类衍生物,可用作医药化工中间体。
- 制备
以噻吩并[3,2-d]嘧啶-2,4-二醇为起始物料,经氯代反应制备得到目标化合物2,4-二氯-噻吩[3,2-D]嘧啶,后与吗啉发生取代反应制备得到目标化合物2-氯-4-(4-吗啉基)噻吩并[3,2-D]嘧啶。其合成反应式如下图:
医药化工
合成路线 1(1. 合成:16234-15-4)
产率:100%
合成条件:at 20℃; for 1 h;
实验步骤:参考实施例2:2-氯-4-吗啉-4-基 - 噻吩并[3,2-d]嘧啶(65)(65)2,4-二氯 - 噻吩并[3,2-d]嘧啶(64)的混合物,( 将8.68g,42.34mmol),吗啉(8.1mL,2.2当量)和MeOH(150mL)在室温下搅拌1小时。 然后过滤反应混合物,用水和MeOH洗涤,得到标题化合物,为白色固体(11.04g,100%)。 EPO 1H NMR(400MHz,J6-DMSO)3.74(4H,t,J = 4.9Hz),3.90(4H,t,J = 4.9Hz),7.40(1H,d,J = 5.6Hz),8.30(IH) ,d,J = 5.6Hz)。
参考文献:
- [1] Patent: WO2006/46031, 2006, A1. Location in patent: Page/Page column 29-30 [2] Patent: US2008/76768, 2008, A1. Location in patent: Page/Page column 7 [3] Patent: US2008/76758, 2008, A1. Location in patent: Page/Page column 73 [4] Patent: WO2008/70740, 2008, A1. Location in patent: Page/Page column 133 [5] Patent: WO2008/73785, 2008, A2. Location in patent: Page/Page column 160 [6] Patent: WO2009/53715, 2009, A1. Location in patent: Page/Page column 64 [7] Patent: US2010/233164, 2010, A1 [8] Patent: WO2011/130628, 2011, A1. Location in patent: Page/Page column 129 [9] Patent: US2013/102595, 2013, A1. Location in patent: Paragraph 0176 [10] Patent: US9335320, 2016, B2. Location in patent: Page/Page column 70; 71 [11] Patent: JP2015/187145, 2015, A. Location in patent: Paragraph 0174 [12] Patent: JP5658565, 2015, B2. Location in patent: Paragraph 0334-0335 [13] Patent: WO2007/122410, 2007, A1. Location in patent: Page/Page column 62-63 [14] Patent: WO2007/127183, 2007, A1. Location in patent: Page/Page column 135-136 [15] Patent: WO2017/90058, 2017, A1. Location in patent: Page/Page column 17 [16] Chemical and Pharmaceutical Bulletin, 2012, vol. 60, # 8, p. 1037 - 1045 [17] European Journal of Medicinal Chemistry, 2012, vol. 57, p. 162 - 175 [18] European Journal of Medicinal Chemistry, 2015, vol. 93, p. 64 - 73 [19] Organic Process Research and Development, 2013, vol. 17, # 1, p. 97 - 107 [20] Patent: US9249156, 2016, B2. Location in patent: Page/Page column 37 [21] Patent: WO2018/85342, 2018, A1. Location in patent: Page/Page column 25; 30; 31 [22] European Journal of Medicinal Chemistry, 2018, vol. 151, p. 836 - 848 [23] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2408 - 2411 [24] Patent: US2011/230476, 2011, A1. Location in patent: Page/Page column 247 [25] Chinese Chemical Letters, 2012, vol. 23, # 6, p. 703 - 706 [26] Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7686 - 7695 [27] Patent: US2011/269244, 2011, A1. Location in patent: Page/Page column [28] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 358 - 365 [29] Patent: CN103980287, 2016, B. Location in patent: Paragraph 0117; 0122; 0123 [30] Patent: CN104292242, 2017, B. Location in patent: Paragraph 0123; 0124; 0125