2-(Chloromethyl)-3-[2-(trifluoromethyl)phenyl]quinazolin-4-one | 1094100-04-5

• 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: 2-(Chloromethyl)-3-[2-(trifluoromethyl)phenyl]quinazolin-4-one
• CAS: 1094100-04-5
• 化学式: C₁₆H₁₀ClF₃N₂O
• 分子量: 338.716
• InChiKey: MTZOWSSXTUSEEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(Chloromethyl)-3-[2-(trifluoromethyl)phenyl]quinazolin-4-one 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 C₂₀H₁₉F₃N₄O
  参考文献：
  名称：

  Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

  摘要：

  Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO2 in 6% H2SO4 in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K2CO3 and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.

  DOI：

  10.1080/00397910902735381
• 作为产物：
  描述：

  邻氨基苯甲酸 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 2-(Chloromethyl)-3-[2-(trifluoromethyl)phenyl]quinazolin-4-one
  参考文献：
  名称：

  Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors

  摘要：

  Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1 alpha transcriptional factor from a high-throughput screen. HIF-1 alpha up-regulation is common in many cancer cells. In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.07.043

文献信息

• Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors
  作者：Wenwei Huang、Ruili Huang、Matias S. Attene-Ramos、Srilatha Sakamuru、Erika E. Englund、James Inglese、Christopher P. Austin、Menghang Xia

  DOI：10.1016/j.bmcl.2011.07.043

  日期：2011.9

  Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1 alpha transcriptional factor from a high-throughput screen. HIF-1 alpha up-regulation is common in many cancer cells. In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16. Published by Elsevier Ltd.
• Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters
  作者：Palle V. R. Acharyulu、P. K. Dubey、P. V. V. Prasada Reddy、Thatipally Suresh

  DOI：10.1080/00397910902735381

  日期：2009.8.20

  Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO2 in 6% H2SO4 in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K2CO3 and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.
• One-pot multicomponent synthesis of medicinally important purine quinazolinone derivatives
  作者：Sanghapal D. Sawant、Mahesuni Srinivas、G. Lakshma Reddy、V. Venkateswar Rao、Parvinder Pal Singh、Ram A. Vishwakarma

  DOI：10.1016/j.tetlet.2012.08.137

  日期：2012.11

  Herein, a protocol that involves microwave-assisted, multicomponent one-pot synthetic strategy for the construction of the medicinally important purine quinazolinone scaffold is reported. A series of compounds are prepared by cyclization and condensation reactions using this approach. The compounds are structural analogs of anticancer agents IC-87114 and CAL-101, which are highly isoform-selective PI3K-delta inhibitors and are presently under clinical investigation for chronic lymphocytic leukemia. (C) 2012 Elsevier Ltd. All rights reserved.