trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1H-quinazoline-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1H-quinazoline-2,4-dione
• 英文别名: 6-methoxy-3-[[4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexyl]methyl]-1H-quinazoline-2,4-dione
• 化学式: C₂₄H₃₂N₄O₆
• 分子量: 472.541
• InChiKey: MMNYGRXCTFTCLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1H-quinazoline-2,4-dione 、 碘甲烷 在 sodium hydride 作用下， 以62%的产率得到trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1-methyl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461

  摘要：

  A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.

  DOI：

  10.1021/op400145w
• 作为产物：
  描述：

  凝血酸 在 palladium 10% on activated carbon 、 氢气 、 N,N'-羰基二咪唑 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -5.0~30.0 ℃ 、517.12 kPa 条件下， 反应 29.79h， 生成 trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461

  摘要：

  A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.

  DOI：

  10.1021/op400145w

文献信息

• Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461
  作者：Matteo Betti、Eva Genesio、Alessandro Panico、Salvatore Sanna Coccone、Paul Wiedenau

  DOI：10.1021/op400145w

  日期：2013.8.16

  A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.