6-chloro-4-cyclopropyl-1-[(4-methoxyphenyl)methyl]-4-(2-pyrazin-2-ylethynyl)-3H-quinazolin-2-one | 157195-65-8

• 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-chloro-4-cyclopropyl-1-[(4-methoxyphenyl)methyl]-4-(2-pyrazin-2-ylethynyl)-3H-quinazolin-2-one
• CAS: 157195-65-8
• 化学式: C₂₅H₂₁ClN₄O₂
• 分子量: 444.92
• InChiKey: AHSUUABWMHQQCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-4-cyclopropyl-1-[(4-methoxyphenyl)methyl]-4-(2-pyrazin-2-ylethynyl)-3H-quinazolin-2-one 在 三氟乙酸 作用下， 反应 96.0h， 以41%的产率得到6-chloro-4-cyclopropyl-3,4-dihydro-4-((2-pyrazinyl)ethynyl)quinazolin-2(1H)-one
  参考文献：
  名称：

  Synthesis of a Series of 4-(Arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones as Novel Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  As part of an ongoing effort to prepare novel non-nucleoside inhibitors of human immunodeficiency virus type-1 (HTV-1) reverse transcriptase (RT), a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones 4aa-1 has been prepared. Target compounds 4a-e were synthesized via addition of various 1-lithio-2-(aryl)alkyne nucleophiles to a 1-protected-4-cyclopropylquinazolin-2(1H)-one (7), followed by deprotection. The 3-methyl compound 4aa was prepared in an analogous manner, with the 3-alkylation performed prior to deprotection. Alternatively, the target compounds 4f-1 were prepared by addition of 1-lithio-2-(trimethylsilyl)acetylene to 7, followed by deprotection and subsequent palladium-catalyzed coupling with various aryl halides, By incorporating an aryl group onto the end of the 4-acetylene functionality, the requirement for a metabolically labile 3-methyl group on the dihydroquinazolinone nucleus has been eliminated. A number of the target compounds were shown to be potent inhibitors of HTV-1 RT. Compound 4a, which had exhibited the most favorable overall biological profile, was' resolved via a four-step procedure to provide the enantiomers 13a and 13b. Compound 13a having the (-)-4(S) configuration was shown to be the active enantiomer and was selected as a candidate for further investigation.

  DOI：

  10.1021/jm00041a023
• 作为产物：
  描述：

  2-氨基-5-氯苯腈 在 正丁基锂 、 magnesium triflate 、 lithium hexamethyldisilazane 作用下， 反应 14.5h， 生成 6-chloro-4-cyclopropyl-1-[(4-methoxyphenyl)methyl]-4-(2-pyrazin-2-ylethynyl)-3H-quinazolin-2-one
  参考文献：
  名称：

  Synthesis of a Series of 4-(Arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones as Novel Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  As part of an ongoing effort to prepare novel non-nucleoside inhibitors of human immunodeficiency virus type-1 (HTV-1) reverse transcriptase (RT), a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones 4aa-1 has been prepared. Target compounds 4a-e were synthesized via addition of various 1-lithio-2-(aryl)alkyne nucleophiles to a 1-protected-4-cyclopropylquinazolin-2(1H)-one (7), followed by deprotection. The 3-methyl compound 4aa was prepared in an analogous manner, with the 3-alkylation performed prior to deprotection. Alternatively, the target compounds 4f-1 were prepared by addition of 1-lithio-2-(trimethylsilyl)acetylene to 7, followed by deprotection and subsequent palladium-catalyzed coupling with various aryl halides, By incorporating an aryl group onto the end of the 4-acetylene functionality, the requirement for a metabolically labile 3-methyl group on the dihydroquinazolinone nucleus has been eliminated. A number of the target compounds were shown to be potent inhibitors of HTV-1 RT. Compound 4a, which had exhibited the most favorable overall biological profile, was' resolved via a four-step procedure to provide the enantiomers 13a and 13b. Compound 13a having the (-)-4(S) configuration was shown to be the active enantiomer and was selected as a candidate for further investigation.

  DOI：

  10.1021/jm00041a023

文献信息

• Synthesis of a Series of 4-(Arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones as Novel Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors
  作者：Thomas J. Tucker、Terry A. Lyle、Catherine M. Wiscount、Susan F. Britcher、Steven D. Young、William M. Sanders、William C. Lumma、Mark E. Goldman、Julie A. O'Brien

  DOI：10.1021/jm00041a023

  日期：1994.7

  As part of an ongoing effort to prepare novel non-nucleoside inhibitors of human immunodeficiency virus type-1 (HTV-1) reverse transcriptase (RT), a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)-ones 4aa-1 has been prepared. Target compounds 4a-e were synthesized via addition of various 1-lithio-2-(aryl)alkyne nucleophiles to a 1-protected-4-cyclopropylquinazolin-2(1H)-one (7), followed by deprotection. The 3-methyl compound 4aa was prepared in an analogous manner, with the 3-alkylation performed prior to deprotection. Alternatively, the target compounds 4f-1 were prepared by addition of 1-lithio-2-(trimethylsilyl)acetylene to 7, followed by deprotection and subsequent palladium-catalyzed coupling with various aryl halides, By incorporating an aryl group onto the end of the 4-acetylene functionality, the requirement for a metabolically labile 3-methyl group on the dihydroquinazolinone nucleus has been eliminated. A number of the target compounds were shown to be potent inhibitors of HTV-1 RT. Compound 4a, which had exhibited the most favorable overall biological profile, was' resolved via a four-step procedure to provide the enantiomers 13a and 13b. Compound 13a having the (-)-4(S) configuration was shown to be the active enantiomer and was selected as a candidate for further investigation.