化学合成。
化学合成
合成路线 1（1. 合成：125872-95-9）
产率：91%
合成条件：Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.33 h; Inert atmosphere Stage #2: for 0.33 h; Inert atmosphere
实验步骤：向1个底部烧瓶中加入6-溴-1H-吲哚（14.88g，76mmol）和THF（150ml），得到深栗色溶液。将烧瓶置于2次扫描中，并在15分钟内分几批加入氢化钠（60wt％）（3.64g，91mmol）。将所得混合物搅拌20分钟，然后通过注射器加入碘甲烷（5.94ml，95mmol）。在几分钟内，观察到放热。搅拌20分钟后，将混合物真空浓缩，将残余物溶于饱和的水溶液中。碳酸氢钠溶液，用DCM（3x）萃取。将合并的有机萃取液用硫酸钠干燥，过滤并浓缩。通过硅胶色谱法（0至40％EtOAc /庚烷）纯化粗产物，得到6-溴-1-甲基-1H-吲哚（14.44g，68.7mmol，91％产率），为浅色油状物。 .H NMR（400MHz，CDCl3）δ= 7.51-7.46（m，2H），7.24-7.19（m，1H），7.03（d，J = 3.1Hz，1H），6.47（dd，J = 0.9） ，3.1Hz，1H），3.77（s，3H）。
参考文献：
- [1] European Journal of Organic Chemistry, 2011, # 20-21, p. 3781 - 3793 [2] Helvetica Chimica Acta, 2006, vol. 89, # 5, p. 936 - 946 [3] Patent: WO2013/25883, 2013, A1. Location in patent: Page/Page column 41-42 [4] Journal of the American Chemical Society, 2013, vol. 135, # 30, p. 10978 - 10981 [5] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1062 - 1067 [6] Organic Process Research and Development, 2018, vol. 22, # 11, p. 1489 - 1499 [7] Patent: EP3205650, 2017, A1. Location in patent: Paragraph 0106; 0249; 0250 [8] Patent: US2016/244475, 2016, A1. Location in patent: Paragraph 0278; 0279 [9] Patent: US2018/162822, 2018, A1. Location in patent: Paragraph 0500 [10] Patent: WO2011/103546, 2011, A1. Location in patent: Page/Page column 141-142 [11] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 2, p. 125 - 128 [12] Patent: US2003/125371, 2003, A1 [13] Patent: US6017945, 2000, A [14] Journal of Organometallic Chemistry, 2011, vol. 696, # 5, p. 1072 - 1083 [15] Patent: WO2011/112995, 2011, A1. Location in patent: Page/Page column 72 [16] Organic Letters, 2012, vol. 14, # 16, p. 4130 - 4133 [17] Chemical Communications, 2012, vol. 48, # 89, p. 11023 - 11025 [18] Patent: US2014/148430, 2014, A1. Location in patent: Paragraph 0379 [19] Organic Letters, 2016, vol. 18, # 21, p. 5496 - 5499 [20] Chemical Communications, 2017, vol. 53, # 33, p. 4593 - 4596 [21] Organic Letters, 2018, vol. 20, # 16, p. 4898 - 4901 [22] Chemistry - An Asian Journal, 2018, vol. 13, # 18, p. 2664 - 2670 [23] European Journal of Medicinal Chemistry, 2018, vol. 160, p. 120 - 132
