2-bromo-6-chloro-3-fluorobenzaldehyde | 1242156-97-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-bromo-6-chloro-3-fluorobenzaldehyde
• 英文别名: 2-Bromo-6-chloro-3-fluoro-benzaldehyde
• CAS: 1242156-97-3
• 化学式: C₇H₃BrClFO
• 分子量: 237.456
• InChiKey: JBCMRZAMPZKYLM-UHFFFAOYSA-N

物化性质

• 沸点：
  254.4±35.0 °C(Predicted)
• 密度：
  1.779±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-6-chloro-3-fluorobenzaldehyde 、 2-碘苯甲酸甲酯 在 lithium chloro-isopropyl-magnesium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以82%的产率得到(±)-3-(2-bromo-6-chloro-3-fluorophenyl)isobenzofuran-1(3H)-one
  参考文献：
  名称：

  A concise synthesis of 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4- b ]pyridin-5(7 H )-ones], 3-aryl-, and alkylphthalides

  摘要：

  A synthetically useful protocol has been developed for the preparation of highly functionalized 3,4-fused spiro[isobenzofuran-3-ones], spiro[furo[3,4-b]pyridin-5(7H)-ones], 3-aryl-, and alkylphthalides. Reaction of 2-iodobenzoate esters and 2-iodopyridine carboxylate esters with i-PrMgCl center dot LiCl in the presence of cyclic ketones under standard Barbier reaction conditions affords 3,4-fused spiro[isobenzofuran-3-ones] and spiro[furo[3,4-b]pyridin-5(7H)-ones] in good to excellent yields. Step-wise addition of i-PrMgCl center dot LiCl to 2-iodobenzoate esters followed by trapping with various aldehydes yields 3-aryl and 3-alkylphthalides; whereas, under similar conditions access to 3-aryl and 3-alylazaphthalides is also possible. Extension of this methodology toward the preparation of 3-n-butylphthalide and chrycolide, a natural product isolated from the leaves and stems of Chrysanthemum coronarium, is also described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.02.051
• 作为产物：
  描述：

  3-溴-1-氯-4-氟苯 、 N,N-二甲基甲酰胺 在 lithium diisopropyl amide 、 ammonium hydroxide 、 水 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 生成 2-bromo-6-chloro-3-fluorobenzaldehyde
  参考文献：
  名称：

  Inhibitors of Bruton's Tyrosine Kinase

  摘要：

  该应用程序根据通用公式I-III披露了5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡啶-3-酮和5-苯基-1H-吡嗪-2-酮衍生物： 其中，变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些化合物抑制Btk。本文披露的化合物对调节Btk的活性并治疗与过度Btk活性相关的疾病有用。这些化合物进一步有助于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有公式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。

  公开号：

  US20100222325A1

文献信息

• Magnetically Driven Agitation in a Tube Mixer Affords Clog-Resistant Fast Mixing Independent of Linear Velocity
  作者：Sarah J. Dolman、Jason L. Nyrop、Jeffrey T. Kuethe

  DOI：10.1021/jo102275n

  日期：2011.2.4

  An economical and simple flow mixer based on magnetically driven agitation in a tube (MDAT) is reported. Mixing via MDAT compared favorably to both Tee and multilaminar mixers at low flow and was successfully used to screen and optimize two challenging organometallic reactions at low temperature without clogging or the need for high dilution.

  据报道，一种基于管内磁驱动搅拌的经济，简单的混流器（MDAT）。在低流量条件下，通过MDAT进行混合比在Tee和多层混合器中都更有利，并且成功地用于筛选和优化低温下两个具有挑战性的有机金属反应，而不会发生堵塞或需要高稀释度的情况。
• Inhibitors of Bruton's tyrosine kinase
  申请人：Roche Palo Alto LLC

  公开号：US08299077B2

  公开（公告）日：2012-10-30

  This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formula I-III: wherein, variables Q, R, X, X′, Y1, Y2, Y2′, Y3, Y4, Y5, m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I-III and at least one carrier, diluent or excipient.

  本申请披露了根据通式I-III制备的5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡嗪-3-酮和5-苯基-1H-吡嗪-2-酮衍生物，其中变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些衍生物可以抑制Btk。本文所披露的化合物可用于调节Btk的活性和治疗与Btk过度活性相关的疾病。这些化合物还可用于治疗与异常B细胞增殖相关的炎症和自身免疫性疾病，如类风湿性关节炎。本申请还披露了包含通式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2403846A1

  公开（公告）日：2012-01-11
• US8299077B2
  申请人：——

  公开号：US8299077B2

  公开（公告）日：2012-10-30
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010100070A1

  公开（公告）日：2010-09-10

  This application discloses compounds according to general Formula (A) wherein, variable Z* is defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula (A) and at least one carrier, diluent or excipient.