6-chloro-4-cyclopropyl-3,4-dihydro-4-ethynyl-1-(4-methoxybenzyl)quinazolin-2(1H)-one | 153800-14-7

• 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-3,4-dihydro-4-ethynyl-1-(4-methoxybenzyl)quinazolin-2(1H)-one
• 英文别名: 6-Chloro-4-cyclopropyl-4-ethynyl-3,4-dihydro-1-(p-methoxybenzyl)-quinazolin-2(1H)-one；6-chloro-4-cyclopropyl-4-ethynyl-3,4-dihydro-1-(p-methoxybenzyl)quinazolin-2(1H)-one；6-chloro-4-cyclopropyl-4-ethynyl-1-[(4-methoxyphenyl)methyl]-3H-quinazolin-2-one
• CAS: 153800-14-7
• 化学式: C₂₁H₁₉ClN₂O₂
• 分子量: 366.847
• InChiKey: JGBBOWJOCHEDMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-4-cyclopropyl-3,4-dihydro-4-ethynyl-1-(4-methoxybenzyl)quinazolin-2(1H)-one 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 生成 6-chloro-4-cyclopropyl-3,4-dihydro-4-(phenylethynyl)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：

  4-甲氧基氯苄 在 正丁基锂 、 magnesium triflate 、 lithium hexamethyldisilazane 作用下， 反应 30.5h， 生成 6-chloro-4-cyclopropyl-3,4-dihydro-4-ethynyl-1-(4-methoxybenzyl)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

文献信息

• Chiral resolution process
  申请人：Merck & Co., Inc.

  公开号：US05457201A1

  公开（公告）日：1995-10-10

  A chiral resolution process is described for the purification of a substituted chiral quinazoline, by salt formation with a resolving agent, followed by crystallization.

  描述了一种手性分离过程，用于通过与一个分离剂形成盐，然后结晶来纯化取代手性喹啉。
• Tucker Thomas J., Lyle Terry A., Wiscount Catherine M., Britcher Susan F.+, J. Med. Chem, 37 (1994) N 15, S 2437-2444
  作者：Tucker Thomas J., Lyle Terry A., Wiscount Catherine M., Britcher Susan F.+

  DOI：——

  日期：——
• US5457201A
  申请人：——

  公开号：US5457201A

  公开（公告）日：1995-10-10