3-(3-bromophenyl)quinazolin-4(3H)-one | 24122-27-8

• 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: 3-(3-bromophenyl)quinazolin-4(3H)-one
• 英文别名: 3-(3-bromo-phenyl)-3H-quinazolin-4-one；3-(3-Bromo-phenyl)-3H-quinazolin-4-one；3-(3-bromophenyl)quinazolin-4-one
• CAS: 24122-27-8
• 化学式: C₁₄H₉BrN₂O
• 分子量: 301.142
• InChiKey: RXVMUOHRYVNNGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-bromophenyl)quinazolin-4(3H)-one 在 potassium phosphate 、 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 9.0h， 生成 7-(2-hydroxypropan-2-yl)-4-(3-(4-oxoquinazolin-3(4H)-yl)-phenyl)-9H-carbazole-1-carboxamide
  参考文献：
  名称：

  Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)

  摘要：

  Bruton's tyrosine,kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous auto-immune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and, selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oXo-3,4-dihydroquinazdlin-3-yl)phenyl]-9H-carbazole-1-carboxarnide 6 (BMS-935177) was selected:to advance into clinical development.

  DOI：

  10.1021/acs.jmedchem.6b00722
• 作为产物：
  描述：

  叔丁基过氧化氢 、 2-amino-N-(3-bromophenyl)benzamide 在 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 10.0h， 以74%的产率得到3-(3-bromophenyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  TBHP作为无金属需氧条件下的甲基源，通过C（sp3）-H键的氧化胺化反应合成喹唑啉-4（3H）-酮和喹唑啉

  摘要：

  在无金属好氧条件下，叔丁基过氧化氢（TBHP）在C（sp 3）-H键的氧化胺化反应中作为甲基源，提供了quinazolin-4（3 H）-one和quinazoline衍生物。

  DOI：

  10.1002/ejoc.201800495

文献信息

• 10.1021/acs.joc.3c02596
  作者：Luo, Wen、Zhang, Chao、Dong, Lin

  DOI：10.1021/acs.joc.3c02596

  日期：——

  The use of amide carbonyl groups of substrates as weakly coordinating directing groups has received a significant amount of attention. Recently, difluoromethylene alkynes have been successfully used in fluorination reactions, resulting in the preparation of various fluorine-containing compounds. This work describes a [4+2] annulation method for creating a range of fluorinated quinolino[2,1-b]quinazolinone

  使用底物的酰胺羰基作为弱配位导向基团已受到广泛关注。近年来，二氟亚甲基炔已成功用于氟化反应，从而制备了各种含氟化合物。这项工作描述了一种 [4+2] 成环方法，用于制备一系列氟化喹啉并[2,1- b ]喹唑啉酮衍生物。该衍生物是通过 Rh(III) 催化的 3-苯基喹唑啉酮和偕二氟亚甲基炔的级联环化形成的。
• TBHP as Methyl Source under Metal-Free Aerobic Conditions To Synthesize Quinazolin-4(3<i>H</i> )-ones and Quinazolines by Oxidative Amination of C(sp³ )-H Bond
  作者：Sushobhan Mukhopadhyay、Dinesh S. Barak、Sanjay Batra

  DOI：10.1002/ejoc.201800495

  日期：2018.6.15

  tert‐Butyl hydroperoxide (TBHP) served as the methyl source under metal‐free aerobic conditions in the oxidative amination of a C(sp3)–H bond to provide quinazolin‐4(3H)‐one and quinazoline derivatives.

  在无金属好氧条件下，叔丁基过氧化氢（TBHP）在C（sp 3）-H键的氧化胺化反应中作为甲基源，提供了quinazolin-4（3 H）-one和quinazoline衍生物。
• Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9<i>H</i>-carbazole-1-carboxamide (BMS-935177)
  作者：George V. De Lucca、Qing Shi、Qingjie Liu、Douglas G. Batt、Myra Beaudoin Bertrand、Rick Rampulla、Arvind Mathur、Lorell Discenza、Celia D’Arienzo、Jun Dai、Mary Obermeier、Rodney Vickery、Yingru Zhang、Zheng Yang、Punit Marathe、Andrew J. Tebben、Jodi K. Muckelbauer、ChiehYing J. Chang、Huiping Zhang、Kathleen Gillooly、Tracy Taylor、Mark A. Pattoli、Stacey Skala、Daniel W. Kukral、Kim W. McIntyre、Luisa Salter-Cid、Aberra Fura、James R. Burke、Joel C. Barrish、Percy H. Carter、Joseph A. Tino

  DOI：10.1021/acs.jmedchem.6b00722

  日期：2016.9.8

  Bruton's tyrosine,kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous auto-immune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and, selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oXo-3,4-dihydroquinazdlin-3-yl)phenyl]-9H-carbazole-1-carboxarnide 6 (BMS-935177) was selected:to advance into clinical development.