405939-39-1 N-BOC-2-氨基-5-溴噻唑

运输信息：常温运输。危险描述：非危险化学品，海关编码2933399990。

化学合成

化学合成

合成路线 1（以二碳酸二叔丁酯和2-氨基-5-溴噻唑单氢溴酸盐为原料）

• 步骤: 将二碳酸二叔丁酯[(Boc)₂O, 100.7g, 0.461mol, 1.2当量]加入到含有2-氨基-5-溴噻唑单氢溴酸盐(100g, 0.385mol, 1.0当量)和4-(二甲基氨基)吡啶(DMAP, 1.18g, 9.7mmol, 0.025当量)的900mL THF和135mL Et₃N混合溶液中；使用冰浴冷却至0℃；室温搅拌过夜；真空浓缩；残余物在EtOAc/庚烷(1:10, 250mL)中室温搅拌过夜，过滤；滤液用盐水洗涤，干燥，过滤，真空浓缩，得到目标产物。
• 条件: With dmap; triethylamine In tetrahydrofuran at 0℃; for 16 h (过夜);
• 收率: 91%
• 参考文献: [1] Synthesis, 2010, #7, p.1091-1096; [2] Patent: WO2018/112136, 2018, A1 (Paragraph 00261); [3] Patent: US2009/36467, 2009, A1 (Page/Page column 64; 72; 73); [4] Patent: US2012/108591, 2012, A1 (Page/Page column 29); [5] Patent: WO2015/25172, 2015, A1 (Page/Page column 118; 119); [6] Patent: WO2009/155389, 2009, A1 (Page/Page column 52-53); [7] Patent: WO2009/155388, 2009, A1 (Page/Page column 62-63); [8] Patent: US2006/178388, 2006, A1 (Page/Page column 69); [9] Patent: WO2008/61236, 2008, A2 (Page/Page column 73-74); [10] Patent: WO2010/83246, 2010, A1 (Page/Page column 57; 59); [11] Patent: US2010/310493, 2010, A1 (Page/Page column 27)

合成路线 2（以Boc₂O和2-氨基-5-溴噻唑氢溴酸盐为原料）

• 步骤: 向15_1(58g, 0.223mol)的DCM(580mL)溶液中加入Boc₂O(58.3g, 0.268mol)和K₂CO₃(62.0g, 0.446mol)；20℃搅拌16小时；过滤；真空浓缩；硅胶色谱法纯化，得到目标产物。
• 条件: With potassium carbonate In dichloromethane at 20℃; for 16 h;
• 收率: 64%
• 参考文献: [1] Bioorganic and Medicinal Chemistry Letters, 2010, vol.20, #19, p.5864-5868; [2] Bioorganic and Medicinal Chemistry Letters, 2013, vol.23, #13, p.3841-3847; [3] Patent: WO2012/6760, 2012, A1 (Page/Page column 48-49); [4] Patent: WO2012/8999, 2012, A2 (Page/Page column 49); [5] European Journal of Medicinal Chemistry, 2018, vol.158, p.896-916; [6] Journal of Medicinal Chemistry, 2005, vol.48, #6, p.1886-1900; [7] Patent: WO2016/46530, 2016, A1 (Page/Page column 76); [8] Patent: WO2017/109488, 2017, A1 (Page/Page column 47)

合成路线 3（以NBS和叔丁基噻唑-2-基氨基甲酸酯为原料）

• 步骤: 将NBS(6.2g, 34.6mmol, 1.1当量)和叔丁基噻唑-2-基氨基甲酸酯(6.3g, 31.5mmol, 1.0当量)在THF(100mL)中搅拌12小时；过滤；柱色谱法纯化，得到目标产物。
• 条件: With N-Bromosuccinimide In tetrahydrofuran at 20℃; for 12 h;
• 收率: 73.9%
• 参考文献: [1] Patent: WO2008/154642, 2008, A2 (Page/Page column 274-275); [2] Bioorganic and Medicinal Chemistry Letters, 2007, vol.17, #19, p.5447-5454; [3] Patent: WO2011/58149, 2011, A1 (Page/Page column 127)