5-溴-3-碘-1H-吡唑并[3,4-B]嘧啶可用作有机合成中间体和医药中间体，主要用于实验室研发过程和化工生产过程中。
医药中间体; 有机合成中间体
路线1：
- 步骤: 向搅拌的溴-二氮杂吲哚III-A-1（1g，5.05mmol）的DMF（14mL）溶液中一次性加入粉碎的KOH颗粒（1.06g，19.03mmol）；11分钟后，加入I₂（1.15g，4.54mmol）并搅拌3.5小时；混合物真空部分浓缩后，用EtOAc（40mL）:饱和NaHCO₃溶液（20mL）稀释并分配，水层用EtOAc（2×20mL）萃取，合并有机层干燥（MgSO₄）、过滤、浓缩得到III-A-1和IV-A-1的1:1混合物；将混合物重新溶解在1,4-二恶烷（14mL）中，用固体NaOH（0.7g）处理，室温搅拌5分钟后加入I₂（0.7g），40℃搅拌23小时；用EtOAc（50mL）稀释，饱和Na₂S₂O₃水溶液（30mL）洗涤，水层用EtOAc（2×30mL）萃取，合并有机萃取物干燥（MgSO₄）、过滤、浓缩得到氮杂吲唑IV-A-I（1.585g，97%）。
- 条件: Stage #1: With iodine; potassium hydroxide In N,N-dimethyl-formamide for 3.50 h; Stage #2: With iodine; sodium hydroxide In 1,4-dioxane at 40℃ for 23 h.
- 产率: 97%
- 参考文献: [1] Patent: WO2010/15803, 2010, A1. Location in patent: Page/Page column 43 [2] Journal of Medicinal Chemistry, 2015, vol. 58, #5, p. 2513-2529 [3] Patent: WO2016/26078, 2016, A1. Location in patent: Paragraph 065 [4] Patent: WO2016/192063, 2016, A1. Location in patent: Paragraph 0112; 0115; 0116 [5] Patent: WO2017/28314, 2017, A1. Location in patent: Paragraph 0125 [6] Bioorganic Chemistry, 2016, vol. 65, p. 146-158 [7] Patent: CN103613591, 2016, B. Location in patent: Paragraph 0342-0344 [8] Patent: WO2006/15124, 2006, A2. Location in patent: Page/Page column 59 [9] Patent: US2008/261921, 2008, A1. Location in patent: Page/Page column 73-74 [10] Patent: WO2009/111279, 2009, A1. Location in patent: Page/Page column 83 [11] Patent: CN108117553, 2018, A. Location in patent: Paragraph 0278; 0279; 0280-0282 [12] ACS Medicinal Chemistry Letters, 2015, vol. 6, #5, p. 543-547 [13] Patent: US2016/137640, 2016, A1. Location in patent: Paragraph 0181; 0182 [14] Patent: WO2015/25025, 2015, A1. Location in patent: Page/Page column 130 [15] Patent: WO2016/192064, 2016, A1. Location in patent: Paragraph 0118-0119
路线2：
- 步骤: 将化合物4b（8mg，0.033mmol）、溴（20μL，0.39mmol）和乙酸（1mL）加入烧瓶中，加热至回流过夜；反应混合物真空浓缩，残余物溶解在EtOAc中，依次用NaHCO₃水溶液和Na₂S₂O₃洗涤，有机层用MgSO₄干燥后浓缩；通过快速色谱法（硅胶，CH₂Cl₂:EtOAc→8:2）纯化残余物，得到化合物4c（5.5mg，52%）。
- 条件: With bromine In acetic acid Heating / reflux
- 产率: 52%
- 参考文献: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, #5, p. 1243-1245 [2] Patent: WO2006/130673, 2006, A1. Location in patent: Page/Page column 86
