N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide | 911416-37-0

• 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: N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide
• 英文别名: N-[3-(2-methoxyethenyl)-6-(4-phenylmethoxybutoxy)pyridin-2-yl]-2,2-dimethylpropanamide
• CAS: 911416-37-0
• 化学式: C₂₄H₃₂N₂O₄
• 分子量: 412.529
• InChiKey: MIVHJFXLPDAXJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 1.0h， 生成 6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-ylamine
  参考文献：
  名称：

  The Synthesis of a Dopamine D₂ Partial Agonist for the Treatment of Schizophrenia

  摘要：

  The synthesis of the phosphoric acid salt of dopamine D-2 partial agonist 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8- one (1) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO4. The optimized synthetic route for the preparation of phosphate salt I consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13. Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude material with the required purity, suitable for use in the subsequent salt formation step. Finally, considerable work was carried out to determine the most stable polymorph of the API. As a result, a robust set of conditions has been developed for the formation of phosphoric acid salt 1, providing the desired polymorph in excellent yield and purity.

  DOI：

  10.1021/op800307k
• 作为产物：
  描述：

  N-[6-(4-benzyloxy-butoxy)-3-formyl-pyridin-2-yl]-2,2-dimethyl-propionamide 、 甲氧基甲基三苯基氯化膦 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以61%的产率得到N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide
  参考文献：
  名称：

  The Synthesis of a Dopamine D₂ Partial Agonist for the Treatment of Schizophrenia

  摘要：

  The synthesis of the phosphoric acid salt of dopamine D-2 partial agonist 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8- one (1) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO4. The optimized synthetic route for the preparation of phosphate salt I consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13. Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude material with the required purity, suitable for use in the subsequent salt formation step. Finally, considerable work was carried out to determine the most stable polymorph of the API. As a result, a robust set of conditions has been developed for the formation of phosphoric acid salt 1, providing the desired polymorph in excellent yield and purity.

  DOI：

  10.1021/op800307k
• 作为试剂：
  描述：

  甲氧基甲基三苯基氯化膦 、 、 potassium tert-butylate 、 四氢呋喃 、 N-[6-(4-benzyloxy-butoxy)-3-formyl-pyridin-2-yl]-2,2-dimethyl-propionamide 在 N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide 、 甲基叔丁基醚 、 Brine 、 silica gel 、 ethyl acetate heptane 、 甲苯 作用下， 以 水 为溶剂， 反应 1.83h， 以gave a yellow oil, (0.75 equivalents), crude N-[6-(4-Benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide (14)的产率得到N-[6-(4-benzyloxy-butoxy)-3-(2-methoxy-vinyl)-pyridin-2-yl]-2,2-dimethyl-propionamide
  参考文献：
  名称：

  Tetrahydro-pyridoazepin-8-ones and related compounds for the treatment of schizophrenia

  摘要：

  本文披露了化学式1的化合物，其中G、D、A、Q、Y、Z和R1至R10在说明书中有定义。还提供了制备化学式1的过程的描述，用于制备化合物的中间体，以及含有这些化合物的制药组合物及其在治疗中枢神经系统疾病和其他疾病中的应用。

  公开号：

  US20060234997A1

文献信息

• WO2006/103559
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/116265
  申请人：——

  公开号：——

  公开（公告）日：——