[6-[(acetyloxy)methyl]-2,7-dimethyl-4-oxoquinazolin-3(4H)-yl]methyl pivalate | 838858-85-8

• 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: [6-[(acetyloxy)methyl]-2,7-dimethyl-4-oxoquinazolin-3(4H)-yl]methyl pivalate
• 英文别名: [6-(acetyloxymethyl)-2,7-dimethyl-4-oxoquinazolin-3-yl]methyl 2,2-dimethylpropanoate
• CAS: 838858-85-8
• 化学式: C₁₉H₂₄N₂O₅
• 分子量: 360.41
• InChiKey: ZHGNXQNKYYOICH-UHFFFAOYSA-N

物化性质

• 沸点：
  496.3±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  85.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [6-[(acetyloxy)methyl]-2,7-dimethyl-4-oxoquinazolin-3(4H)-yl]methyl pivalate 在 氢溴酸 、 溶剂黄146 作用下， 生成 6-(bromomethyl)-3,4-dihydro-2,7-dimethyl-4-oxo-3-<(pivaloyloxy)methyl>quinazoline
  参考文献：
  名称：

  Chemical Development of ZD9331:  Synthesis of a Bromomethylquinazolinone Avoiding a Nonselective Radical Bromination

  摘要：

  An efficient regiospecific synthesis of ZD9331 Pivaloyloxymethyl (POM) Bromide ( 4) has been accomplished via ZD9331 Quinacetate HCl ( 15) avoiding a nonselective bromination. The original route used a radical bromination on a substrate with three methyl groups, which generated a range of bromomethyl derived compounds that carried through to the final active pharmaceutical ingredient (API). A strategy, based on the Zinin reaction, was developed to synthesize the required bromomethyl compound in a regioselective manner. This approach was successfully scaled to manufacture a tonne of material.

  DOI：

  10.1021/op060049a
• 作为产物：
  描述：

  (2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl acetate hydrochloride 、 特戊酸氯甲酯 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 19.0h， 以62%的产率得到[6-[(acetyloxy)methyl]-2,7-dimethyl-4-oxoquinazolin-3(4H)-yl]methyl pivalate
  参考文献：
  名称：

  [EN] SYNTHETIC METHOD FOR THE PREPARATION OF QUINAZOLIN-4-ONE DERIVATIVE
  [FR] METHODE SYNTHETIQUE

  摘要：

  公开号：

  WO2005012260A3

文献信息

• [EN] SYNTHETIC METHOD<br/>[FR] METHODE SYNTHETIQUE
  申请人：BTG INT LTD

  公开号：WO2005012260A2

  公开（公告）日：2005-02-10

  A quinazolin-4-one derivative of formula (I), may be made by a process including the step of cyclization an amide of formula (II), to form a quinazolin-4-one derivative of formula (III).

  公式（I）的喹唑啉-4-酮衍生物，可通过包括环化公式（II）的酰胺的步骤来制备，以形成公式（III）的喹唑啉-4-酮衍生物。
• Synthetic method for the preparation of quinazolin-4-one derivative
  申请人：Godfrey Aydon Andrew

  公开号：US20060189804A1

  公开（公告）日：2006-08-24

  A quinazolin-4-one derivative of formula (I), may be made by a process including the step of cyclization an amide of formula (II), to form a quinazolin-4-one derivative of formula (III).

  公式（I）的喹唑啉-4-酮衍生物，可通过包括环化公式（II）的酰胺的步骤制成，以形成公式（III）的喹唑啉-4-酮衍生物。
• Trouble with Potassium Carbonate and Centrifuges:  Mass Transfer and Scale-Up Effects in the Manufacture of ZD9331 POM Quinacetate
  作者：Jonathan D. Moseley、Parminder Bansal、Sharon A. Bowden、A. Edward M. Couch、Ivo Hubacek、Günter Weingärtner

  DOI：10.1021/op0501693

  日期：2006.1.1

  Manufacture of ZD9331 pivaloyloxymethyl (POM) quinacetate, was progressively scaled up from large-scale lab to pilot plant to full-scale production. The specific surface area of the potassium carbonate used for the deprotonation was found to be critical as successive increases in the mass transfer area were counteracted by the reduced mass transfer efficiency, linked to the reactor size and impeller effectiveness. Furthermore, a change from a pressure filter to a centrifuge meant that the washing efficiency was similarly limited by mass transfer, with the rate of dissolution of the undesired regioisomer on the centrifuge being too low for the shorter wash time. These problems were overcome, resulting in two successful manufacturing campaigns with over 1 tonne of POM quinacetate produced well within specification in eight batches.
• SYNTHETIC METHOD FOR THE PREPARATION OF QUINAZOLIN-4-ONE DERIVATIVES
  申请人：BTG INTERNATIONAL LIMITED

  公开号：EP1675831A2

  公开（公告）日：2006-07-05