8-溴-11-乙基-5-甲基-5,11-二氢-6H-二吡啶并[3,2-B:2',3'-E][1,4]二氮杂卓-6-酮 | 162109-00-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 8-溴-11-乙基-5-甲基-5,11-二氢-6H-二吡啶并[3,2-B:2',3'-E][1,4]二氮杂卓-6-酮
• 英文名称: 2-bromo-5-ethyl-10-methyl-5,10-dihydro-4,5,6,10-tetraazadibenzo[a,d]cyclohepten-11-one
• 英文别名: 8-bromo-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one；8-bromo-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2'.3'-e][1.4]diazepin-6-one；13-Bromo-2-ethyl-9-methyl-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 162109-00-4
• 化学式: C₁₄H₁₃BrN₄O
• 分子量: 333.187
• InChiKey: BJEIQNJCEZCSQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  8-溴-11-乙基-5-甲基-5,11-二氢-6H-二吡啶并[3,2-B:2',3'-E][1,4]二氮杂卓-6-酮 在 boron trifluoride acetic acid complex 、 palladium diacetate 、 caesium carbonate 、 三苯基膦 作用下， 以 溶剂黄146 、 乙腈 为溶剂， 反应 29.5h， 生成 BILR 355
  参考文献：
  名称：

  奈韦拉平类似物HIV NNRT抑制剂中试过程的开发

  摘要：

  描述了奈韦拉平类似物1的中试合成。由取代的吡啶原料和4-羟基喹啉分八步制备该化合物。关键的转化涉及在钯催化下将芳基卤化物一锅转化为芳酸，然后通过原位生成的BH 3 / THF选择性还原成芳基乙醇中间体2。所有阶段均以10-150千克规模进行。

  DOI：

  10.1021/op8000756
• 作为产物：
  描述：

  5-溴-2-氯-3-吡啶羰酰氯 在 sodium hexamethyldisilazane 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 52.75h， 生成 8-溴-11-乙基-5-甲基-5,11-二氢-6H-二吡啶并[3,2-B:2',3'-E][1,4]二氮杂卓-6-酮
  参考文献：
  名称：

  奈韦拉平类似物HIV NNRT抑制剂中试过程的开发

  摘要：

  描述了奈韦拉平类似物1的中试合成。由取代的吡啶原料和4-羟基喹啉分八步制备该化合物。关键的转化涉及在钯催化下将芳基卤化物一锅转化为芳酸，然后通过原位生成的BH 3 / THF选择性还原成芳基乙醇中间体2。所有阶段均以10-150千克规模进行。

  DOI：

  10.1021/op8000756

文献信息

• Non-nucleoside reverse transcriptase inhibitors
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US20040106791A1

  公开（公告）日：2004-06-03

  Compounds represented by formula I: 1 wherein R 1 is H, halogen, (C 1-4 )alkyl, O(C 1-4 )alkyl, and haloalkyl; R 2 is H or (C 1-4 )alkyl; R 3 is H or (C 1-4 )alkyl; R 4 is (C 1-4 )alkyl, (C 1-4 )alkyl(C 3-7 )cycloalkyl, or (C 3-7 )cycloalkyl; and Q is a fused phenyl-5 or 6-membered saturated heterocycle having one to two heteroatoms selected from O and N, said Q being optionally substituted with hydroxy, or (C 1-4 )alkyl which in turn maybe optionally substituted with pyridinyl-N-oxide or C(O)OR wherein R is H or (C 1-4 )alkyl; or a salt thereof. The compounds have inhibitory activity against Wild Type, and single and double mutants strains, of HIV.

  化合物的化学式表示为I： 其中R1为H、卤素、(C1-4)烷基、O(C1-4)烷基和卤代烷基；R2为H或(C1-4)烷基；R3为H或(C1-4)烷基；R4为(C1-4)烷基、(C1-4)烷基(C3-7)环烷基或(C3-7)环烷基；Q为融合的带有一个到两个来自O和N的杂原子的饱和的含有5个或6个成员的苯基杂环，所述Q可以选择地用羟基或(C1-4)烷基取代，而(C1-4)烷基可以选择地用吡啶-N-氧化物或C(O)OR取代，其中R为H或(C1-4)烷基；或其盐。这些化合物对HIV的野生型、单突变体和双突变体菌株具有抑制活性。
• Process and intermediates for making non-nucleoside HIV-1 reverse transcriptase inhibitors
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US20040002489A1

  公开（公告）日：2004-01-01

  A process and novel intermediates for making compounds of the formula I: 1 wherein: R 2 is selected from the group consisting of H, F, Cl, C 1-4 alkyl, C 3-4 cycloalkyl and CF 3 ; R 4 is H or Me; R 5 is H, Me or Et, with the proviso that R 4 and R 5 are not both Me, and if R 4 is Me then R 5 cannot be Et; R 11 is Me, Et, cyclopropyl, propyl, isopropyl, or cyclobutyl; and Q is selected from the group consisting of: 2

  一种用于制备化合物I的过程和新型中间体： 其中： R2选自H、F、Cl、C1-4烷基、C3-4环烷基和CF3； R4为H或Me； R5为H、Me或Et，但要求R4和R5不能同时为Me，且若R4为Me，则R5不能为Et； R11选自Me、Et、环丙基、丙基、异丙基或环丁基； Q选自以下组合之一：
• Synthesis of [¹⁴C]- and [¹³C₆]-labeled potent HIV non-nucleoside reverse transcriptase inhibitor
  作者：Bachir Latli、Matt Hrapchak、Carl A. Busacca、Dhileepkumar Krishnamurthy、Chris H. Senanayake

  DOI：10.1002/jlcr.1572

  日期：2009.3

  uinolinyl)oxy}ethyl}-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one, (1), labeled with carbon-14 in the quinoline–benzene ring, in one of the pyridine rings of the dipyridodiazepinone tricyclic moiety, and in the side chain, was prepared in three different syntheses with specific activities ranging from 44 to 47 mCi/mmol (1.63–1.75 GBq/mmol). In the first synthesis, 5,11-dihydro-11-ethyl-8-(2-hydro

  5,11-Dihydro-11-ethyl-5-methyl-8-2-(1-oxido-4-quinolinyl)oxy}ethyl}-6H-dipyrido[3,2-b:2',3'- e][1,4]diazepin-6-one，(1)，在喹啉-苯环、二吡啶并二氮杂酮三环部分的吡啶环之一和侧链中用碳 14 标记，制备如下三种不同的合成物，比活性范围为 44 到 47 mCi/mmol (1.63–1.75 GBq/mmol)。在第一次合成中，5,11-二氢-11-乙基-8-(2-羟乙基)-5-甲基-6H-二吡啶并[3,2-b:2',3'-e][1,4] diazepin-6-one (2) 与 4-hydroxyquinoline, [benzo-14C(U)]- 偶联，使用 Mitsunobu 的反应条件，然后用 3-氯过氧苯甲酸氧化喹啉氮，得到 ([14C]- (1a)) 的放射化学产率为
• 10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds - poster presentations Session 19, Sunday, June 14 to Thursday, June 18, 2009
  作者：William Wheeler

  DOI：10.1002/jlcr.1776

  日期：——

  The poster session is a series of papers dealing with a conglomeration of all of the previous sessions. Cristian Postolache, the fourth of the Wiley Young Scientist Award winners gave a Poster in this session. Copyright © 2010 John Wiley & Sons, Ltd.

  海报展示环节由一系列论文组成，涵盖了之前所有环节的内容。第四位威利青年科学家奖获得者克里斯蒂安-波斯托拉奇（Cristian Postolache）在此环节发表了一篇海报。Copyright © 2010 John Wiley & Sons, Ltd. 版权所有。
• Novel 8-Substituted Dipyridodiazepinone Inhibitors with a Broad-Spectrum of Activity against HIV-1 Strains Resistant to Non-nucleoside Reverse Transcriptase Inhibitors
  作者：Jeff A. O'Meara、Christiane Yoakim、Pierre R. Bonneau、Michael Bös、Michael G. Cordingley、Robert Déziel、Louise Doyon、Jianmin Duan、Michel Garneau、Ingrid Guse、Serge Landry、Eric Malenfant、Julie Naud、William W. Ogilvie、Bounkham Thavonekham、Bruno Simoneau

  DOI：10.1021/jm050255t

  日期：2005.8.1

  A series of novel 8-substituted dipyridodiazepinone-based inhibitors were investigated for their antiviral activity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virus. Our efforts have resulted in a series of benzoic acid analogues that are potent inhibitors of HIV-1 replication against a panel of HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIS). Furthermore, the combination of good antiviral potency, a broad spectrum of activity, and an excellent pharmacokinetic profile provides strong justification for the further development of compound 7 as a potential treatment for wild type and NNRTI-resistant HIV-1 infection.