2-(甲硫基)-4-氨基嘧啶-5-甲酸乙酯主要作为医药中间体，用于药物合成。
医药
路线1：氨解反应
- 步骤: 向2L三颈烧瓶中加入4-氯-2-（甲硫基）嘧啶-5-羧酸乙酯（100g，0.43mol）、THF（500mL）和TEA（186mL，1.29mol）；分批加入氢氧化铵（28％水溶液，400mL），保持内部温度低于30℃；2小时后，加入水（1000mL），真空蒸馏除去THF；将所得固体过滤并在50℃下真空干燥，得到4-氨基-2-（甲硫基）嘧啶-5-羧酸乙酯（90g，99％）。
- 条件: With ammonium hydroxide; triethylamine In tetrahydrofuran; water at 30℃; for 2 h.
- 收率: 99%
- 参考文献: [1] Patent: US2015/31674, 2015, A1. Location in patent: Paragraph 0319 [2] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 12, p. 1241 - 1246 [3] Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5520 - 5541 [4] Patent: WO2014/182829, 2014, A1. Location in patent: Page/Page column 42 [5] Patent: WO2015/120049, 2015, A1. Location in patent: Page/Page column 126; 127 [6] Patent: WO2016/191172, 2016, A1. Location in patent: Page/Page column 56-57 [7] Patent: WO2013/134243, 2013, A1. Location in patent: Page/Page column 15-16 [8] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179 [9] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387 [10] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 578 - 599 [11] Patent: WO2014/151682, 2014, A1. Location in patent: Page/Page column 52; 53 [12] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4606 - 4616 [13] Patent: US2016/75720, 2016, A1. Location in patent: Paragraph 0259 [14] Organic and Biomolecular Chemistry, 2010, vol. 8, # 9, p. 2164 - 2173 [15] Patent: WO2006/135824, 2006, A1. Location in patent: Page/Page column 15 [16] Patent: US6451804, 2002, B1 [17] Patent: US5733913, 1998, A [18] Patent: WO2007/36791, 2007, A1. Location in patent: Page/Page column 55 [19] Patent: US2007/167469, 2007, A1. Location in patent: Page/Page column 4 [20] Patent: US2008/176874, 2008, A1. Location in patent: Page/Page column 4 [21] Patent: EP1364950, 2003, A1. Location in patent: Page/Page column 222 [22] Patent: WO2014/144737, 2014, A1. Location in patent: Paragraph 00619 [23] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 4, p. 413 - 418 [24] Patent: WO2015/84936, 2015, A1. Location in patent: Page/Page column 91 [25] Patent: WO2017/19429, 2017, A1. Location in patent: Page/Page column 9; 15; 16
路线2：甲基化反应
- 步骤: 将碘甲烷（2.6g，18mmol）加入到在N,N-二甲基甲酰胺（150mL）中的4-氨基-2-巯基嘧啶-5-羧酸乙酯（3.0g，15mmol）的热溶液（50℃）中；在室温下搅拌20分钟；真空除去溶剂，用水洗涤固体残余物；真空干燥后，得到所需产物（3.1g，97％）。
- 条件: at 20 - 50℃; for 0.33 h.
- 收率: 97%
- 参考文献: [1] Patent: US2005/20590, 2005, A1. Location in patent: Page/Page column 27 [2] Patent: US6150373, 2000, A
路线3：氨解反应
- 步骤: 向四氢呋喃（200mL）中加入4-氯-2-甲硫基-嘧啶-5-羧酸乙酯（15.0g，65mmol）和三乙胺（25mL）；加入35mL氢氧化铵水溶液；在室温下搅拌1.5小时后，再加入30mL氢氧化铵水溶液，继续搅拌1小时；将反应混合物真空浓缩，并在乙酸乙酯和饱和碳酸氢钠水溶液之间分配；有机层用盐水洗涤，用硫酸镁干燥，过滤，并真空浓缩；加入乙酸乙酯和己烷，过滤收集所得固体，得到10.84g（79％）4-氨基-2-甲硫基-嘧啶-5-羧酸乙酯。
- 条件: With triethylamine In tetrahydrofuran; hexane; ethyl acetate
- 收率: 79%
- 参考文献: [1] Patent: US2003/73668, 2003, A1 [2] Patent: US2002/55513, 2002, A1 [3] Patent: US6498163, 2002, B1 [4] Patent: US2004/224958, 2004, A1
