5-bromo-1-methyl-1H-imidazole-4-carbonitrile | 1669415-69-3

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 5-bromo-1-methyl-1H-imidazole-4-carbonitrile
• 英文别名: 5-Bromo-1-methyl-1H-imidazole-4-carbonitrile；5-bromo-1-methylimidazole-4-carbonitrile
• CAS: 1669415-69-3
• 化学式: C₅H₄BrN₃
• 分子量: 186.011
• InChiKey: HROWRHSFQVRYEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-methyl-1H-imidazole-4-carbonitrile 在 copper(l) iodide 、 盐酸羟胺 、 palladium diacetate 、 2-氯-1,3-二甲基氯化咪唑啉 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 pivalic anhydride 、 sodium hydroxide 、 sodium t-butanolate 、 N,N'-二甲基乙二胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 甲苯 为溶剂， 20.0~100.0 ℃ 、122.02 kPa 条件下， 反应 63.5h， 生成 N,N-二环丙基-4-[(1,5-二甲基-1H-吡唑-3-基)氨基]-6-乙基-1,6-二氢-1-甲基-咪唑并[4,5-d]吡咯并[2,3-b]吡啶-7-甲酰胺
  参考文献：
  名称：

  Ni-Catalyzed C–H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543

  摘要：

  BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.

  DOI：

  10.1021/acs.joc.5b00572
• 作为产物：
  描述：

  1-甲基-1H-咪唑-4-甲腈 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以86%的产率得到5-bromo-1-methyl-1H-imidazole-4-carbonitrile
  参考文献：
  名称：

  [EN] ALKYNYL-(HETEROARYL)-CARBOXAMIDE HCN1 INHIBITORS
  [FR] INHIBITEURS D'ALCYNYLE- (HÉTÉROARYL)-CARBOXAMIDE HCN1

  摘要：

  本发明提供了公式（I）的化合物，公式（I）中R1、R2或R3如本文所述，以及其药学上可接受的盐。此外，本发明涉及制备公式（I）的化合物，包含它们的药物组合物以及作为药物使用的方法。

  公开号：

  WO2021110574A1
• 作为试剂：
  描述：

  5-bromo-1-methyl-1H-imidazole-4-carbonitrile 、 ethyl 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxylate 在 5-bromo-1-methyl-1H-imidazole-4-carbonitrile 作用下， 以84的产率得到ethyl 4-(4-cyano-1-methyl-1H-imidazol-5-yl)-1-ethyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  J. Org. Chem. 2015, 80, 6001-6011

  摘要：

  DOI：

文献信息

• [EN] PROCESS FOR THE PREPARATION OF N,N-DICYCLOPROPYL-4-(1,5-DIMETHYL-1H-PYRAZOL-3-YLAMINO)-6-ETHYL-1-METHYL-1,6-DIHYDROIMIDAZO[4,5-d]PYRROLO[2,3-b]PYRIDINE-7-CARBOXAMIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION DU N,N-DICYCLOPROPYL-4-(1,5-DIMÉTHYL-1H-PYRAZOL-3YLAMINO)-6-ÉTHYL-1-MÉTHYL-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE-7-CARBOXAMIDE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015031562A1

  公开（公告）日：2015-03-05

  The invention relates to an improved process for synthesizing N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide of the formula: (I) Compound (I) is currently in clinical trials for the treatment of myeloproliferative disorders, such as polycythaemia vera, thrombocythaemia and primary myelofibrosis.

  该发明涉及一种改进的合成N,N-二环丙基-4-(1,5-二甲基-1H-吡唑-3-基氨基)-6-乙基-1-甲基-1,6-二氢咪唑并[4,5-d]吡咯并[2,3-b]吡啶-7-羧酰胺的方法，该化合物的化学式为：(I) 化合物(I)目前正在临床试验中用于治疗骨髓增殖性疾病，如真性红细胞增多症、血小板增多症和原发性骨髓纤维化。
• [EN] ALKYNYL-(HETEROARYL)-CARBOXAMIDE HCN1 INHIBITORS<br/>[FR] INHIBITEURS D'ALCYNYLE- (HÉTÉROARYL)-CARBOXAMIDE HCN1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021110574A1

  公开（公告）日：2021-06-10

  The present invention provides compounds of formula (I), Formula (I) wherein R1, R2 or R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

  本发明提供了公式（I）的化合物，公式（I）中R1、R2或R3如本文所述，以及其药学上可接受的盐。此外，本发明涉及制备公式（I）的化合物，包含它们的药物组合物以及作为药物使用的方法。
• Mono-Oxidation of Bidentate Bis-phosphines in Catalyst Activation: Kinetic and Mechanistic Studies of a Pd/Xantphos-Catalyzed C–H Functionalization
  作者：Yining Ji、R. Erik Plata、Christopher S. Regens、Michael Hay、Michael Schmidt、Thomas Razler、Yuping Qiu、Peng Geng、Yi Hsiao、Thorsten Rosner、Martin D. Eastgate、Donna G. Blackmond

  DOI：10.1021/jacs.5b01913

  日期：2015.10.21

  Kinetic, spectroscopic, crystallographic, and computational studies probing a Pd-catalyzed C-H arylation reaction reveal that mono-oxidation of the bis-phosphine ligand is critical for the formation of the active catalyst. The bisphosphine mono-oxide is shown to be a hemilabile,bidentate ligand for palladium. Isolation of the oxidative addition adduct, with structural elucidation by X-ray analysis, showed that the mono-oxide was catalytically competent, giving the same reaction rate in the productive reaction as the Pd(II)/xantphos precursor. A dual role for the carboxylate base in both catalyst activation and reaction turnover was demonstrated, along with the inhibiting effect of excess phosphine ligand. The generality of the role of phosphine mono-oxide complexes in Pd-catalyzed coupling processes is discussed.
• Ni-Catalyzed C–H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543
  作者：Monica A Fitzgerald、Omid Soltani、Carolyn Wei、Dimitri Skliar、Bin Zheng、Jun Li、Jacob Albrecht、Michael Schmidt、Michelle Mahoney、Richard J. Fox、Kristy Tran、Keming Zhu、Martin D. Eastgate

  DOI：10.1021/acs.joc.5b00572

  日期：2015.6.19

  BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.
• J. Org. Chem. 2015, 80, 6001-6011
  作者：

  DOI：——

  日期：——