1-(2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine

• 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: 1-(2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine
• 英文别名: N-[(E)-[2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)phenyl]methylideneamino]methanamine
• 化学式: C₁₄H₁₀Br₂FN₃O₃
• 分子量: 447.058
• InChiKey: SZLNIFNJINCJSX-FBCYGCLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine 在 potassium phosphate monohydrate 、 dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) 、 二碳酸二叔丁酯 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、344.75 kPa 条件下， 反应 110.0h， 生成 N-[3-氟-4-[[1-甲基-6-(1H-吡唑-4-基)-1H-吲唑-5-基]氧基]苯基]-1-(4-氟苯基)-1,2-二氢-6-甲基-2-氧代-3-吡啶甲酰胺
  参考文献：
  名称：

  Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

  摘要：

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.

  DOI：

  10.1021/op400317z
• 作为产物：
  描述：

  2,4-二溴-5-羟基苯甲醛 在 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 1-(2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine
  参考文献：
  名称：

  Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

  摘要：

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.

  DOI：

  10.1021/op400317z

文献信息

• AMIDOPHENOXYINDAZOLES USEFUL AS INHIBITORS OF C-MET
  申请人：LI Tiechao

  公开号：US20100022529A1

  公开（公告）日：2010-01-28

  The present invention provides amidophenoxyindazole compounds useful in the treatment of cancer.

  这项发明提供了在癌症治疗中有用的酰胺基苯氧基吲唑化合物。
• [EN] AMIDOPHENOXYINDAZOLES USEFUL AS INHIBITORS OF C-MET<br/>[FR] COMPOSÉS AMIDO-PHÉNOXY-INDAZOLE UTILISÉS COMME INHIBITEURS DU C-MET
  申请人：LILLY CO ELI

  公开号：WO2010011538A1

  公开（公告）日：2010-01-28

  The present invention provides amidophenoxyindazole compounds useful in the treatment of cancer.

  本发明提供了一种在癌症治疗中有用的酰胺基苯氧基吲唑化合物。
• US8030302B2
  申请人：——

  公开号：US8030302B2

  公开（公告）日：2011-10-04
• USRE43878E1
  申请人：——

  公开号：USRE43878E1

  公开（公告）日：2012-12-25
• Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an <i>N</i>1<i>-</i>Methylindazole
  作者：Neil J. Kallman、Chin Liu、Matthew H. Yates、Ryan J. Linder、J. Craig Ruble、Eugene F. Kogut、Lawrence E. Patterson、Dana L. T. Laird、Marvin M. Hansen

  DOI：10.1021/op400317z

  日期：2014.4.18

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.