117976-90-6 雷贝拉唑钠

运输信息：冰袋运输。危险描述：WGK Germany:3；海关编码:2933399090；存储类别:11 - 可燃固体；危险性类别:急性毒性 类别4 经口；危害水生环境-长期危害 类别4。非危险化学品。

作为二代质子泵抑制剂，用于治疗胃溃疡、消化性溃疡、胃食管反流性疾病、卓-艾氏综合症等酸相关性疾病，通过抑制胃H+/K+-ATPase减少胃酸分泌，达到治愈胃及十二指肠溃疡和胃-食道返流症的效果。

医药

路线1：

• 步骤：向装有回流冷凝器的3颈圆底烧瓶中，氮气气氛下加入中间体II（2- [4-（3-甲氧基丙氧基）-3-甲基-1-氧基吡啶-2-基甲基亚磺酰基] -1H-苯并咪唑）、甲醇、甲醇钠（30% w/w）、四甲基乙二胺和RuCl₃水合物（40% w/w钌）；加热至50℃反应10小时，HPLC分析收率95%；冷却至室温，浓缩至一半体积，加水稀释，硅藻土过滤；用乙酸调节pH至6-7，亚硫酸钠调节，乙酸乙酯萃取；加入50%氢氧化钠水溶液，室温搅拌24小时，结晶得到标题产物多晶型1，纯度>99.7%，收率91%。
• 条件：50℃，10小时；20℃，24小时；氮气气氛
• 收率：91%
• 参考文献：[1] Patent: US2009/76277, 2009, A1. Location in patent: Page/Page column 5-6 [2] Patent: US2009/76277, 2009, A1. Location in patent: Page/Page column 5 [3] Patent: EP1921075, 2008, A2. Location in patent: Page/Page column 7 [4] Patent: US2009/76277, 2009, A1. Location in patent: Page/Page column 5 [5] Patent: EP1921075, 2008, A2. Location in patent: Page/Page column 8

路线2：

• 步骤：将氢氧化钠溶于乙醇中搅拌溶解；加入2-(((4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基)甲基)亚磺酰基)-1H-苯并咪唑搅拌至溶解；缓慢加入二异丙基乙醚或叔丁基甲基醚，沉淀析出产物，过滤收集。
• 条件：20℃（溶解）；加入二异丙基乙醚或叔丁基甲基醚（2000ml或160ml），室温沉淀
• 收率：100%
• 参考文献：[1] Patent: US2007/225502, 2007, A1. Location in patent: Page/Page column 5 [2] Patent: US2007/225502, 2007, A1. Location in patent: Page/Page column 8-9 [4] Patent: WO2003/101452, 2003, A1. Location in patent: Page 2 [5] Organic Process Research and Development, 2009, vol. 13, # 5, p. 896 - 899 [6] Patent: EP1452533, 2004, A1. Location in patent: Page 8 [7] Patent: EP1452533, 2004, A1. Location in patent: Page 9 [8] Patent: EP1452533, 2004, A1. Location in patent: Page 8-9 [9] Patent: US2004/180935, 2004, A1. Location in patent: Page/Page column 7 [10] Patent: WO2003/82858, 2003, A1. Location in patent: Page/Page column 12-13 [11] Patent: WO2009/116072, 2009, A2. Location in patent: Page/Page column 15-16 [12] Patent: CN106674198, 2017, A. Location in patent: Paragraph 0026-0027 [13] Patent: EP1452533, 2004, A1. Location in patent: Page 9 [14] Patent: US2004/180935, 2004, A1. Location in patent: Page/Page column 6-7 [15] Patent: WO2003/82858, 2003, A1. Location in patent: Page/Page column 13 [16] Patent: US2007/225502, 2007, A1. Location in patent: Page/Page column 4-5 [17] Patent: WO2008/35192, 2008, A2. Location in patent: Page/Page column 5 [18] Patent: WO2008/35192, 2008, A2. Location in patent: Page/Page column 5 [19] Patent: WO2006/120701, 2006, A1. Location in patent: Page/Page column 5; 6 [20] Patent: CN104311540, 2016, B. Location in patent: Paragraph 0039-0040 [21] Patent: CN106317019, 2017, A. Location in patent: Paragraph 0077; 0078; 0079; 0080 [22] Patent: EP1818331, 2007, A1. Location in patent: Page/Page column 6 [23] Patent: WO2008/17020, 2008, A2. Location in patent: Page/Page column 23-24 [24] Synthetic Communications, 2009, vol. 39, # 2, p. 278 - 290 [25] Patent: WO2009/133572, 2009, A2. Location in patent: Page/Page column 7 [26] Patent: WO2010/6904, 2010, A2. Location in patent: Page/Page column 19 [27] Patent: WO2010/4571, 2010, A2. Location in patent: Page/Page column 3-4 [28] Patent: EP1921075, 2008, A2. Location in patent: Page/Page column 8 [29] Patent: WO2011/4281, 2011, A1. Location in patent: Page/Page column 4; 5 [30] Patent: WO2012/146643, 2012, A1. Location in patent: Page/Page column 14; 15 [31] Patent: WO2014/91450, 2014, A1. Location in patent: Page/Page column 16-17 [32] Patent: WO2008/155780, 2008, A2. Location in patent: Page/Page column 11 [33] Patent: WO2008/155780, 2008, A2. Location in patent: Page/Page column 12