1-(4-(1-cyanocyclobutyl)phenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile | 1236409-75-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(4-(1-cyanocyclobutyl)phenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile
• 英文别名: 1-(4-(1-cyanocyclobutyl)phenyl)-4-methoxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile；1-[4-(1-cyanocyclobutyl)phenyl]-4-methoxy-6-oxo-2,3-dihydropyridine-5-carbonitrile
• CAS: 1236409-75-8
• 化学式: C₁₈H₁₇N₃O₂
• 分子量: 307.352
• InChiKey: MYSGEIOKHFGNQW-UHFFFAOYSA-N

物化性质

• 沸点：
  549.1±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氰胺 、 1-(4-(1-cyanocyclobutyl)phenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.5h， 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
• 作为产物：
  描述：

  1-(4-氨基-苯基)-环丁烷甲腈 在 草酰氯 、 溶剂黄146 、 1-丙基磷酸酐 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲基叔丁基醚 、 乙酸乙酯 为溶剂， 反应 114.5h， 生成 1-(4-(1-cyanocyclobutyl)phenyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile
  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

文献信息

• 4-AMINO-7,8-DIHYDROPYRIDO[4,3-d]PYRIMIDIN-5(6H)-ONE DERIVATIVES
  申请人：Aspnes Gary E.

  公开号：US20100197591A1

  公开（公告）日：2010-08-05

  The invention provides compounds of the general Formula (I) where R 1 , R 2 , and A are defined herein, as well as the preparation, compositions and uses thereof.

  这项发明提供了一般式（I）的化合物 其中R1、R2和A在此处定义，以及其制备、组成和用途。
• 4-AMINO-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE DERIVATIVES
  申请人：Pfizer Inc.

  公开号：EP2393811A1

  公开（公告）日：2011-12-14
• [EN] 4-AMINO-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 4-AMINO-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE
  申请人：PFIZER

  公开号：WO2010089686A1

  公开（公告）日：2010-08-12

  The invention provides compounds of the general Formula (I) where R1, R2, and A are defined herein, as well as the preparation, compositions and uses thereof.