4-氯-6-硝基喹唑啉主要作为医药合成中间体,用于制备各类含喹唑啉结构的药物分子,在抗疟、抗肿瘤等药物研发中具有重要应用。
医药中间体
合成路线 1(1. 合成:19815-16-8)
产率:93.5%
合成条件:at 90℃; for 3 h;
实验步骤:将4-羟基-6-硝基喹唑啉(化合物5)(3.8g,0.02mol)置于100ml烧瓶中,缓慢加入40ml亚硫酰氯和1ml N,N-二甲基甲酰胺。 将混合物加热至90℃,使固体完全溶解,反应进行3小时(此时发现检测完全),减压蒸发亚硫酰氯,得到棕色固体4 - 氯-6-硝基喹唑啉(化合物6)3.92。 g,产率93.5%,HPLC纯度99.67%。 HNMR(300MHz,CDCl3)89.56(s,1H),8.39(d,J = 1.5Hz 1H),8.76(d,J = 1.5Hz,J = 6.0Hz,1H),8.77(d,J = 6.0Hz,1H)。
参考文献:
- [1] Patent: CN108373452, 2018, A. Location in patent: Paragraph 0010; 0024; 0036-0041; 0050-0053 [2] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 12, p. 3974 - 3980 [3] Chinese Journal of Chemistry, 2014, vol. 32, # 6, p. 538 - 544 [4] Patent: WO2014/177038, 2014, A1. Location in patent: Paragraph 00255-00256 [5] Tetrahedron Letters, 2012, vol. 53, # 6, p. 674 - 677 [6] Journal of Medicinal Chemistry, 2003, vol. 46, # 20, p. 4313 - 4321 [7] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 4, p. 1135 - 1138 [8] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3544 - 3552 [9] Patent: EP2090575, 2009, A1. Location in patent: Page/Page column 59 [10] European Journal of Medicinal Chemistry, 2009, vol. 44, # 10, p. 4021 - 4027 [11] Journal of Medicinal Chemistry, 2009, vol. 52, # 13, p. 3915 - 3926 [12] Journal of the American Chemical Society, 2009, vol. 131, # 37, p. 13286 - 13296 [13] Journal of Medicinal Chemistry, 2013, vol. 56, # 14, p. 5757 - 5772 [14] Medicinal Chemistry Research, 2013, vol. 22, # 9, p. 4096 - 4109 [15] ChemMedChem, 2013, vol. 8, # 6, p. 928 - 933 [16] Patent: WO2014/89546, 2014, A1. Location in patent: Page/Page column 0095 [17] Patent: CN106432205, 2017, A. Location in patent: Paragraph 0043; 0044; 0045