206257-41-2

基本信息
4-氯-7-溴喹啉-3-羧酸乙酯
Ethyl 4-chloro-7-broMoquinoline-3-carboxylate
7-bromo-4-chloro-3-Quinolinecarboxylic acid ethyl ester
7-BROMO-4-CHLORO-QUINOLINE-3-CARBOXYLIC ACID ETHYL ESTER
3-Quinolinecarboxylic acid, 7-bromo-4-chloro-, ethyl ester
物理化學(xué)性質(zhì)
制備方法

208580-23-8

206257-41-2
以7-溴-4-羥基喹啉-3-羧酸乙酯(DK-I-49-1,11.0 g,37.1 mmol)為原料,在N,N-二甲基甲酰胺(0.1 mL,1.3 mmol)和二氯甲烷(50 mL)的混合溶劑中,加熱至35-40℃。在30分鐘內(nèi)緩慢滴加草酰氯(5.2 g,40.9 mmol)至反應(yīng)混合物中。隨后,將反應(yīng)混合物在回流溫度(38-40℃)下加熱1小時(shí)。反應(yīng)完成后,將所得棕色溶液冷卻至20-25℃。用二氯甲烷(150 mL)稀釋反應(yīng)混合物,然后緩慢加入25%碳酸鉀水溶液(12.5 g碳酸鉀溶于50 mL水)進(jìn)行中和。分離有機(jī)層和水層,水層用二氯甲烷(50 mL)萃取。合并有機(jī)層,用25%碳酸鉀水溶液(12.5 g碳酸鉀溶于50 mL水)洗滌。合并的有機(jī)層用硫酸鎂干燥。通過旋轉(zhuǎn)蒸發(fā)除去溶劑,產(chǎn)物殘余物用己烷(50 mL)漿化。過濾固體產(chǎn)物,并用己烷(25 mL×2)洗滌兩次。干燥固體,得到目標(biāo)產(chǎn)物4-氯-7-溴喹啉-3-羧酸乙酯(DK-I-54-1,7.2 g,收率61%),為灰白色固體。產(chǎn)物結(jié)構(gòu)通過1H NMR、13C NMR和HRMS確認(rèn):1H NMR (300 MHz, DMSO) δ 9.15 (s, 1H), 8.36 (d, J = 1.9 Hz, 1H), 8.28 (d, J = 9.0 Hz, 1H), 7.98 (dd, J = 9.0, 1.9 Hz, 1H), 4.44 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz, DMSO) δ 164.04, 151.40, 149.74, 142.34, 132.67, 131.88, 127.50, 126.64, 124.70, 123.96, 62.55, 14.46; HRMS m/z calculated for C12H10BrClNO2 (M + H)+ 313.9583, found 314.05.
參考文獻(xiàn):
[1] Patent: WO2016/196961, 2016, A1. Location in patent: Paragraph 00150
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 6, p. 2422 - 2446
[3] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 8, p. 1487 - 1490