CAS: 256376-65-5; 1-(2-Fluorobenzyl)-1H-Pyrazolo[3,4-B]Pyridine-3-Carbonitrile

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3-碘-1H-吡唑并[3,4-B]吡啶置于1,1'-双(二苯基膦)二茂铁,四(三苯基膦)钯,Potassium Carbonate,锌体系中,用 N,N-二甲基乙酰胺,N,N-二甲基甲酰胺 用作溶剂,化学反应 12.0H,反应生成1-(2-氟苄基)-1H-吡唑并[3,4-B]吡啶-3-甲腈
参考文献:用于治疗炎症性肠病的新型 Hdhodh 抑制剂的发现和优化
标题:用于治疗炎症性肠病的新型 Hdhodh 抑制剂的发现和优化
摘要:作为嘧啶核苷酸从头合成的关键限速酶,人二氢乳清酸脱氢酶( H Dhodh)被认为是治疗自身免疫性疾病(包括炎症性肠病(ibd))的已知靶标.在此,通过筛选包含 5091 个分子的活性化合物库,将具有 1 H-吡唑并[3,4-B ]吡啶支架的 Bay 41-2272 鉴定为h Dhodh 抑制剂.进一步优化得到2-(1-(2-氯-6-氟苄基)-1 H-吡咯并[2,3-B ]吡啶-3-基)-5-环丙基嘧啶-4-胺( W2),其为被发现是最有前途的类药物化合物,对h Dhodh 具有有效的抑制活性(ic 50 = 173.4 Nm).化合物w2表现出可接受的药代动力学特征,并以剂量依赖性方式减轻由葡聚糖硫酸钠诱导的急性溃疡性结肠炎的严重程度.值得注意的是,W2对溃疡性结肠炎的治疗效果优于h Dhodh抑制剂维多氟地莫和janus激酶(jak)抑制剂托法替布.综上所述,W2是一种很有前景的h
Doi:10.1021/acs.Jmedchem.3C01365

专利信息

专利号:US-8957210-B2
优先权日:2011-12-12
标题:Method for synthesizing 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-formamidine hydrochloride
发明人：LI JIN; YANG XIAOYU; ZHU JINGWEI; YANG MINMIN; WU XIHAN
权利人:PHARMABLOCK NANJING R & D CO LTD
摘要:The present invention relates to the field of chemical synthesis, and in particular to a method for synthesizing 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-formamidine hydrochloride, which is an important intermediate of Riociguat that is an anti-thromboembolic-disease medicine. The method is characterized in that: 3-iodo-1H-pyrazolo[3,4-b]pyridine is used as a raw material; the raw material is reacted with fluorobenzyl bromide to form a compound (10); the compound (10) is reacted with zinc cyanide to form a compound (6); the compound (6) is reacted with sodium methoxide, ammonium chloride, acetic acid and methanol to form a compound (8); and the compound (8) is reacted with chlorine hydride gas to form 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-formamidine hydrochloride. The method has the characteristics of cheap and readily available raw materials, high yield, mild reaction conditions and the like, and is a synthesis method having a large-scale preparation value.