4-chloro-1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one | 1354545-56-4

• 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: 4-chloro-1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one
• 英文别名: 4-Chloro-1-methoxy-2-nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one；1-chloro-4-methoxy-3-nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one
• CAS: 1354545-56-4
• 化学式: C₁₂H₁₂ClNO₄
• 分子量: 269.685
• InChiKey: IKKYWRVEGKAEMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one 在 盐酸 、 甲酸 作用下， 以 甲醇 、 乙二醇甲醚 为溶剂， 反应 1.67h， 生成 (1S,2S,3R,4R)-3-[5-chloro-2-((S)-1-methoxy-7-(morpholin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-ylamino)pyrimidin-4-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v
• 作为产物：
  描述：

  1-氯-4-甲氧基-2,3-二甲基苯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 四丁基硫酸氢铵 、 potassium carbonate 、 potassium nitrate 、 三氟乙酸 、 potassium hydroxide 作用下， 以 乙醇 、 甲基叔丁基醚 、 水 、 氯苯 为溶剂， 反应 29.0h， 生成 4-chloro-1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v

文献信息

• Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122
  作者：Shawn P. Allwein、Renee C. Roemmele、James J. Haley、Dale R. Mowrey、Daniel E. Petrillo、James J. Reif、Diane E. Gingrich、Roger P. Bakale

  DOI：10.1021/op200313v

  日期：2012.1.20

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.