3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-8-甲醛 | 935758-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-8-甲醛
• 中文别名: 3-氧代-3,4-二氢-2H-苯并[B][1,4]噁嗪-8-甲醛
• 英文名称: 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carbaldehyde
• 英文别名: 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-8-carbaldehyde；3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carbaldehyde；3-oxo-4H-1,4-benzoxazine-8-carbaldehyde
• CAS: 935758-15-9
• 化学式: C₉H₇NO₃
• 分子量: 177.159
• InChiKey: MYWCPPXIQWAZKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-8-甲醛 在 盐酸 、 potassium tert-butylate 、 氯磷酸二乙酯 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 ethyl 6-(2-oxoethyl)-4H-imidazo[5,1-c][1,4]benzoxazin-3-carboxylate
  参考文献：
  名称：

  Development of an Efficient Large-Scale Synthesis for a 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety

  摘要：

  The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis NUS demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.

  DOI：

  10.1021/op100103v
• 作为产物：
  描述：

  ethyl (2-formyl-6-nitrophenoxy)acetate 在 铁粉 、 氯化铵 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 以7.1 kg的产率得到3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-8-甲醛
  参考文献：
  名称：

  Development of an Efficient Large-Scale Synthesis for a 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety

  摘要：

  The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis NUS demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.

  DOI：

  10.1021/op100103v

文献信息

• Substituted dihydropyridines and methods of use
  申请人：Hurt Ray Clarence

  公开号：US20070112015A1

  公开（公告）日：2007-05-17

  Compounds are provided that are modulators of the C5a receptor. The compounds are substituted dihydropyridines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activtation of C5a receptors.

  提供了调节C5a受体的化合物。这些化合物是取代二氢吡啶，并可用于制药组合物、治疗涉及C5a受体病理性激活的疾病和障碍的方法。
• WO2007/51062
  申请人：——

  公开号：——

  公开（公告）日：——
• Organic Process Research and Development 2010, 14, 859-867
  作者：

  DOI：——

  日期：——
• [EN] SUBSTITUTED DIHYDROPYRIDINES AND METHODS OF USE<br/>[FR] DIHYDROPYRIDINES SUBSTITUEES ET LEURS METHODES D'UTILISATION
  申请人：CHEMOCENTRYX INC

  公开号：WO2007051062A2

  公开（公告）日：2007-05-03

  [EN] Compounds are provided that are modulators of the C5a receptor. The compounds are substituted dihydropyridines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activtation of C5a receptors.
  [FR] L'invention porte sur des composés modulateurs du récepteur C5a. Lesdits composés sont des dihydropyridines substituées utilisables dans des préparations pharmaceutiques. L'invention porte également sur des méthodes de traitement de maladies et de troubles impliquant l'activation pathologique du récepteur C5a.
• Development of an Efficient Large-Scale Synthesis for a 4<i>H</i>-imidazo[5,1-<i>c</i>][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety
  作者：Nicola Giubellina、Paolo Stabile、Gilles Laval、Alcide D. Perboni、Zadeo Cimarosti、Pieter Westerduin、Jason W. B. Cooke

  DOI：10.1021/op100103v

  日期：2010.7.16

  The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis NUS demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.