21852-50-6 3,4,5-三甲氧基苄溴

3,4,5-三甲氧基苄溴作为有机合成中间体，广泛应用于医药、农药等领域的有机合成反应中，例如参与芳香族取代反应构建复杂分子结构。

有机合成中间体; 医药合成

合成路线 1（1. 合成：21852-50-6）

产率：100% 合成条件：With phosphorus tribromide In benzene at 20℃; 实验步骤：通用方法：在无水苯（15mL）和三溴化磷（0.5mL）中的苄醇（1mmol）并在室温下搅拌，以定量收率得到各自的苄基溴，通常进行后处理。 参考文献：

• [1] Journal of Steroid Biochemistry and Molecular Biology, 2013, vol. 137, p. 332 - 344 [2] Chemistry - A European Journal, 2015, vol. 21, # 28, p. 10031 - 10038 [3] Medicinal Chemistry Research, 2015, vol. 24, # 8, p. 3143 - 3156 [4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 5, p. 1630 - 1642 [5] Synthetic Communications, 1987, vol. 17, # 7, p. 877 - 892 [6] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 14, p. 3771 - 3774 [7] Organic Letters, 2017, vol. 19, # 8, p. 2054 - 2057 [8] Organic and Biomolecular Chemistry, 2016, vol. 14, # 4, p. 1382 - 1394 [9] Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1648 - 1655 [10] Journal of Organic Chemistry, 2007, vol. 72, # 6, p. 2251 - 2254 [11] Tetrahedron Letters, 2016, vol. 57, # 52, p. 5931 - 5934 [12] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 5, p. 938 - 956 [13] Tetrahedron Letters, 2009, vol. 50, # 25, p. 3070 - 3073 [14] European Journal of Organic Chemistry, 2009, # 34, p. 6034 - 6042 [15] Bioconjugate Chemistry, 2016, vol. 27, # 9, p. 2132 - 2148 [16] Patent: US2009/18369, 2009, A1. Location in patent: Page/Page column 5 [17] Patent: EP1916251, 2008, A1. Location in patent: Page/Page column 10-11 [18] Patent: US2008/234369, 2008, A1. Location in patent: Page/Page column 3 [19] Patent: US2008/233208, 2008, A1. Location in patent: Page/Page column 3 [20] Patent: US2008/306028, 2008, A1. Location in patent: Page/Page column 5-6 [21] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 497 - 505 [22] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 21, p. 6748 - 6757 [23] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 3, p. 173 - 175 [24] Anales de Quimica, 1995, vol. 91, # 1-2, p. 83 - 88 [25] Synthesis, 2010, # 6, p. 953 - 958 [26] Patent: US2015/18566, 2015, A1. Location in patent: Paragraph 0387; 0388 [27] Journal of Natural Products, 2008, vol. 71, # 3, p. 313 - 320 [28] Chinese Journal of Chemistry, 2010, vol. 28, # 6, p. 950 - 960 [29] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5573 - 5581 [30] Carbohydrate Research, 1997, vol. 301, # 3-4, p. 95 - 109 [31] Journal of Organic Chemistry, 1994, vol. 59, # 15, p. 4285 - 4296 [32] Heterocycles, 1991, vol. 32, # 5, p. 965 - 973 [33] Tetrahedron, 1981, vol. 37, # 23, p. 3977 - 3980 [34] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1243 - 1252 [35] Phosphorus, Sulfur and Silicon and the Related Elements, 1993, vol. 75, # 1-4, p. 35 - 38 [36] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 2, p. 157 - 160 [37] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 10, p. 2417 - 2425 [38] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 22, p. 2549 - 2551 [39] Tetrahedron, 2003, vol. 59, # 40, p. 7961 - 7966 [40] Journal of Medicinal Chemistry, 2005, vol. 48, # 2, p. 556 - 568 [41] Medicinal Chemistry Research, 2002, vol. 11, # 2, p. 116 - 136 [42] Journal of Chemical Crystallography, 2005, vol. 35, # 3, p. 227 - 232 [43] Organic Letters, 2007, vol. 9, # 21, p. 4271 - 4274 [44] Organic and Biomolecular Chemistry, 2006, vol. 4, # 23, p. 4281 - 4284 [45] Patent: US2009/43109, 2009, A1. Location in patent: Page/Page column title page; sheet 2; 9 [46] European Journal of Organic Chemistry, 2009, # 1, p. 141 - 145 [47] Chemistry Letters, 2010, vol. 39, # 4, p. 324 - 325 [48] Chemical and Pharmaceutical Bulletin, 2011, vol. 59, # 7, p. 880 - 884 [49] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 18, p. 5321 - 5333 [50] Journal of Fluorescence, 2011, vol. 21, # 1, p. 393 - 407 [51] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 125 - 136 [52] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 18, p. 5971 - 5975 [53] Journal of Medicinal Chemistry, 2014, vol. 57, # 4, p. 1252 - 1275 [54] Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 2092 - 2098 [55] European Journal of Medicinal Chemistry, 2014, vol. 86, p. 740 - 751 [56] Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 23, p. 5571 - 5577 [57] ChemMedChem, 2014, vol. 9, # 11, p. 2565 - 2579 [58] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 8, p. 902 - 907 [59] RSC Advances, 2015, vol. 5, # 100, p. 82153 - 82158 [60] Organic and Biomolecular Chemistry, 2015, vol. 13, # 40, p. 10136 - 10149 [61] Angewandte Chemie - International Edition, 2014, vol. 53, # 47, p. 12907 - 12911 [62] Angew. Chem., 2014, vol. 126, # 47, p. 13121 - 13125,5 [63] Chemical Biology and Drug Design, 2016, p. 97 - 109 [64] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 18, p. 4075 - 4099 [65] ChemMedChem, 2016, vol. 11, # 20, p. 2347 - 2360 [66] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 36 - 51 [67] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 13, p. 3285 - 3297 [68] Journal of the American Chemical Society, 2017, vol. 139, # 4, p. 1460 - 1463 [69] Journal of Medicinal Chemistry, 2017, vol. 60, # 9, p. 4062 - 4073 [70] Tetrahedron Letters, 2016, vol. 57, # 14, p. 1540 - 1543 [71] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 666 - 679 [72] Chemical Biology and Drug Design, 2018, vol. 92, # 2, p. 1419 - 1428 [73] Patent: CN108503561, 2018, A. Location in patent: Paragraph 0033; 0038; 0039 [74] Journal of Enzyme Inhibition and Medicinal Chemistry, 2018, vol. 33, # 1, p. 1554 - 1564 [75] Bioorganic Chemistry, 2019, vol. 83, p. 535 - 548 [76] Patent: CN108727222, 2018, A. Location in patent: Paragraph 0012; 0013; 0022-0024

合成路线 2（2. 合成：21852-50-6）

产率：43% 合成条件：With KBr-K 222 complex; 1,2-dimethoxy-4-methylbenzene In tetrahydrofuran at 60℃; for 0.08 h; 实验步骤：以下是原位形成鎓盐的一般程序，然后进行模拟标记（加入亲核试剂）。向干燥的小瓶中加入咪唑，嘧啶或苯并咪唑前体（0.1mmol）和无水二氯甲烷（0.2ml）。盖上小瓶，然后滴加三氟甲磺酸甲酯（12R1,1.05当量），将小瓶在室温下搅拌过夜。在这些条件下，鎓盐通常是可溶的。然后加入亲核试剂2当量的溶液，接着加入10L的1M的3,4-二甲氧基甲苯（0.01mmol）的无水THF溶液作为内标。将小瓶置于微波管中，并在60℃的预选温度下连续冷却照射5-15分钟。完成该程序后，取出样品并通过GC-MS分析。使用以下溶液作为亲核试剂：KX-K222复合物（X = F，Br，1）在无水乙腈（0.1M）中用于模拟18F，76Br和124I标记。 MeLi（3.0M在THF中）用于C标记。在后一种情况下，用四氢呋喃代替二氯甲烷制备鎓盐。形成白色微晶沉淀，但加入甲基锂后反应进行良好。由化合物1,3,4a和4b制备的鎓盐的结构（在每种情况下，抗衡离子为三氟甲磺酸酯，CF 3 SO 3 - ）如下：OMe Me OMe E，-S化合物5 N \ OMe（来自cpd） 1）Me化合物6（来自cpd.3）Me Con s Me Me Meon A-Ph --- N化合物7（来自cpds.4a或4b）Me下面表1中的反应条件概述形成上述各种鎓盐。 参考文献：

• [1] Patent: WO2005/23317, 2005, A1. Location in patent: Page/Page column 17-18 [2] Patent: WO2005/23317, 2005, A1. Location in patent: Page/Page column 17-18