化学合成。
化学合成
合成路线 1（1. 合成：1440-60-4）
产率：98%
合成条件：With triethylamine In dichloromethane at 0 - 20℃; for 6 h;
实验步骤：通用方法：在0℃下向吗啉（14a; 4.50mL，51.45mmol）和三乙胺（7.90mL，56.68mmol）的CH 2 Cl 2（80mL）溶液中缓慢加入2-氯乙酰氯（6a; 3.70mL，46.45mmol）。 C。 将反应混合物在室温下搅拌6小时，然后用CH 2 Cl 2稀释，用饱和NaHCO 3和盐水洗涤，经MgSO 4干燥并过滤。 减压浓缩残余物，得到 - 氯代酰胺15aa（7.55g，99％），为浅黄色液体。
参考文献：
- [1] Canadian Journal of Chemistry, 2004, vol. 82, # 5, p. 622 - 630 [2] Molecules, 2015, vol. 20, # 11, p. 19984 - 20013 [3] Synthetic Communications, 1998, vol. 28, # 22, p. 4257 - 4272 [4] Patent: WO2012/52843, 2012, A1. Location in patent: Page/Page column 73-74 [5] Chemistry - A European Journal, 2012, vol. 18, # 29, p. 8978 - 8986 [6] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 8, p. 1115 - 1121 [7] Organic Letters, 2005, vol. 7, # 8, p. 1653 - 1656 [8] Tetrahedron, 2007, vol. 63, # 30, p. 7187 - 7212 [9] Chemical Biology and Drug Design, 2012, vol. 80, # 6, p. 918 - 928,11 [10] Chemical Biology and Drug Design, 2012, vol. 80, # 6, p. 918 - 928 [11] Chemical Biology and Drug Design, 2013, vol. 82, # 2, p. 156 - 166 [12] Heterocycles, 1991, vol. 32, # 5, p. 965 - 973 [13] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 13, p. 3405 - 3413 [14] Russian Journal of General Chemistry, 2014, vol. 84, # 8, p. 1539 - 1542 [15] Zhurnal Obshchei Khimii, 2014, vol. 84, # 8, p. 1316 - 1319,4 [16] Journal of the American Chemical Society, 1919, vol. 41, p. 460 [17] Journal of Biological Chemistry, 1915, vol. 21, p. 150 [18] Gazzetta Chimica Italiana, 1951, vol. 81, p. 98,102 [19] Journal of Heterocyclic Chemistry, 1993, vol. 30, # 1, p. 119 - 123 [20] Journal of Heterocyclic Chemistry, 1994, vol. 31, # 2, p. 297 - 303 [21] Arzneimittel-Forschung/Drug Research, 2002, vol. 52, # 11, p. 817 - 821 [22] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 14, p. 3836 - 3840 [23] Patent: WO2011/160084, 2011, A1. Location in patent: Page/Page column 40 [24] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 338 - 347 [25] Tetrahedron Letters, 2015, vol. 56, # 8, p. 1011 - 1014 [26] European Journal of Organic Chemistry, 2015, vol. 2015, # 19, p. 4098 - 4101 [27] Journal of the Serbian Chemical Society, 2015, vol. 80, # 11, p. 1367 - 1374 [28] European Journal of Medicinal Chemistry, 2016, vol. 118, p. 34 - 46 [29] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 608 - 621 [30] Patent: KR2016/7347, 2016, A. Location in patent: Paragraph 0311; 0312; 0318; 0319; 0320 [31] Patent: CN101921247, 2016, B. Location in patent: Paragraph 0024-0026 [32] Patent: CN106146410, 2016, A. Location in patent: Paragraph 0126; 0127 [33] Patent: WO2017/99424, 2017, A1. Location in patent: Paragraph 183; 184 [34] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 234 - 245 [35] Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 968 - 977 [36] Patent: US2018/230123, 2018, A1. Location in patent: Paragraph 0629-0630 [37] Patent: US2654754, 1950,
