trans-4-(6-methoxy-2,4-dioxo-1,4-dihydroquinazolin-3-ylmethyl)cyclohexanecarboxylic acid methyl ester

• 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-4-(6-methoxy-2,4-dioxo-1,4-dihydroquinazolin-3-ylmethyl)cyclohexanecarboxylic acid methyl ester
• 英文别名: trans-methyl 4-((6-methoxy-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)cyclohexanecarboxylate；methyl 4-[(6-methoxy-2,4-dioxo-1H-quinazolin-3-yl)methyl]cyclohexane-1-carboxylate
• 化学式: C₁₈H₂₂N₂O₅
• 分子量: 346.383
• InChiKey: LOZBZCHIECEXJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1H-quinazoline-2,4-dione	——	C24H32N4O6	472.541
  ——	trans-6-methoxy-3-{4-[4-(2-methoxyacetyl)piperazine-1-carbonyl]cyclohexylmethyl}-1-methyl-1H-quinazoline-2,4-dione	——	C25H34N4O6	486.568

反应信息

• 作为反应物：
  描述：

  trans-4-(6-methoxy-2,4-dioxo-1,4-dihydroquinazolin-3-ylmethyl)cyclohexanecarboxylic acid methyl ester 在 N,N'-羰基二咪唑 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 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
• 作为产物：
  描述：

  凝血酸 在 palladium 10% on activated carbon 、 氢气 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 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-4-(6-methoxy-2,4-dioxo-1,4-dihydroquinazolin-3-ylmethyl)cyclohexanecarboxylic acid methyl ester
  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.