作为中间体用于医药合成,具体用途未明确说明,主要通过上述方法制备。
医药
路线1:
- 原料:4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1H-吡唑(8.2g,41mmol)、K₂CO₃(12g,82mmol)、2-(三甲基甲硅烷基)乙氧基甲基氯(7.8mL,43mmol)
- 溶剂:N-甲基吡咯烷酮(NMP,60mL)
- 条件:室温(20℃)、氮气(N₂)保护、搅拌16小时
- 步骤:向4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1H-吡唑的NMP溶液中依次加入K₂CO₃和2-(三甲基甲硅烷基)乙氧基甲基氯,搅拌反应后,用EtOAc稀释,依次用饱和NaHCO₃、水、盐水洗涤,干燥、浓缩、真空干燥得产物
- 收率:86%
- 参考文献:[1] Patent: WO2011/149874, 2011, A2. Location in patent: Page/Page column 81-82;[2] Patent: WO2016/25918, 2016, A1. Location in patent: Paragraph 96-98;[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, #10, p. 3075-3080;[4] Patent: WO2015/95767, 2015, A1. Location in patent: Page/Page column 325;[5] Patent: WO2013/131609, 2013, A1. Location in patent: Page/Page column 112;[6] Patent: US2008/153813, 2008, A1. Location in patent: Page/Page column 7;[7] Patent: WO2018/114786, 2018, A1. Location in patent: Page/Page column 141-142;[8] Patent: EP1982986, 2008, A1. Location in patent: Page/Page column 233;[9] Patent: WO2008/57512, 2008, A2. Location in patent: Page/Page column 97;[10] Patent: US2007/82900, 2007, A1. Location in patent: Page/Page column 153;[11] Patent: US2007/105864, 2007, A1. Location in patent: Page/Page column 205;[12] Patent: US2007/117804, 2007, A1. Location in patent: Page/Page column 137-138;[13] Patent: WO2011/130146, 2011, A1. Location in patent: Page/Page column 83-84;[14] Patent: WO2012/58174, 2012, A1. Location in patent: Page/Page column 43; 44;[15] Patent: EP2857400, 2015, A1. Location in patent: Paragraph 315.A;[16] Patent: WO2016/123391, 2016, A1. Location in patent: Page/Page column 87; 88
路线2:
- 原料:4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1H-吡唑(348mg,1.8mmol)、氢化钠(60%分散体,86mg,2.15mmol)、三甲基甲硅烷基乙氧基甲基氯(358mg,2.15mmol,381μL)
- 溶剂:N,N-二甲基甲酰胺(DMF,5mL)
- 条件:阶段1:60℃加热5分钟;阶段2:冷却后滴加试剂,60℃搅拌16小时
- 步骤:将4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1H-吡唑溶于DMF,加入氢化钠,加热后滴加三甲基甲硅烷基乙氧基甲基氯,反应后用EtOAc稀释,洗涤、干燥、浓缩,柱色谱纯化得产物
- 收率:61%
- 参考文献:[1] Patent: US2006/142307, 2006, A1. Location in patent: Page/Page column 7