| 1492906-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• CAS: 1492906-25-8
• 化学式: C₁₈H₁₅N₅O
• 分子量: 317.35
• InChiKey: SQAHNWZCYNDUNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  103.71
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  甲醇 、 、 sodium methylate 在 甲烷磺酸 作用下， 反应 20.5h， 以2.61 kg的产率得到1-(4-(4-amino-2-methoxy-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-phenyl)cyclobutanecarbonitrile
  参考文献：
  名称：

  Exploratory Process Development of a Novel Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor

  摘要：

  A practical large-scale synthesis was developed for 1, a DGAT-1 inhibitor, involving an aza-Michael reaction, amidation, Dieckman cyclization, and conjugate addition of cyanamide followed by cyclization, to form the fused 4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-5-one scaffold. The enabled process presented here substantially improved safety (in particular, due to eliminating a nitration step and optimizing a high-energy intermediate step), reproducibility, and scalability, resulting in delivery of a multikilogram quantity of the API with high purity. The controls of API quality and particle size were also discussed.

  DOI：

  10.1021/op400215h
• 作为产物：
  描述：

  ethyl 3-(2-cyano-N-(4-(1-cyanocyclobutyl)phenyl)acetamido)propanoate 在 草酰氯 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 46.0h， 生成
  参考文献：
  名称：

  Exploratory Process Development of a Novel Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor

  摘要：

  A practical large-scale synthesis was developed for 1, a DGAT-1 inhibitor, involving an aza-Michael reaction, amidation, Dieckman cyclization, and conjugate addition of cyanamide followed by cyclization, to form the fused 4-amino-7,8-dihydropyrido[4,3-d]pyrimidin-5-one scaffold. The enabled process presented here substantially improved safety (in particular, due to eliminating a nitration step and optimizing a high-energy intermediate step), reproducibility, and scalability, resulting in delivery of a multikilogram quantity of the API with high purity. The controls of API quality and particle size were also discussed.

  DOI：

  10.1021/op400215h