4-(bromomethyl)-N-(tert-butyl)benzamide | 162330-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(bromomethyl)-N-(tert-butyl)benzamide
• 英文别名: 4-(bromomethyl)-N-tert-butylbenzamide
• CAS: 162330-18-9
• 化学式: C₁₂H₁₆BrNO
• 分子量: 270.169
• InChiKey: MORJJJHUIQUITG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-(bromomethyl)-N-(tert-butyl)benzamide 在 palladium on activated charcoal 正丁基锂 、 氢气 作用下， 以 乙醇 、 丙酮 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 27.5h， 生成 N-tert-butyl-4-<2-(1-methyl-2-oxopiperidine-5-yl)-2-methylethylene>benzamide
  参考文献：
  名称：

  Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones

  摘要：

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).

  DOI：

  10.1016/0223-5234(94)90104-x
• 作为产物：
  描述：

  对溴甲基苯甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-(bromomethyl)-N-(tert-butyl)benzamide
  参考文献：
  名称：

  发现新型5-甲基-1H-吡唑衍生物作为潜在的抗前列腺癌药物：设计，合成，分子建模和生物学评估

  摘要：

  雄激素受体（AR）信号传导是前列腺癌（PCa）病情发展的核心驱动力，而且AR被证明甚至是去势抵抗性前列腺癌（CRPC）的有效治疗靶标。在此，基于两个前导化合物T3和10e通过片段剪接策略进行结构修饰，从而发现了一系列5-甲基-1 H-吡唑衍生物。AR报道基因检测表明，化合物A13和A14是有效的AR拮抗剂。该系列中的某些化合物比恩杂鲁胺更有效地抑制PCa LNCaP细胞的生长。A13和A14与人肝微粒体中的10e相比，还显示出改善的代谢稳定性。

  DOI：

  10.1111/cbdd.13173

文献信息

• 5-甲基-1H-吡唑衍生物及其制备方法和应用
  申请人：山东大学

  公开号：CN107903213A

  公开（公告）日：2018-04-13

  本发明公开了一种5‑甲基‑1H‑吡唑衍生物及其制备方法和应用。该类化合物具有如通式(I)所示的结构。本发明还提供该化合物的制备方法及应用。本发明的化合物对前列腺癌细胞表现出了良好的生长抑制活性，可用于制备抗肿瘤药物。
• Supramolecular Organoplatinum(IV) Chemistry: Sequential Introduction of Amide Hydrogen Bonding Groups
  作者：Richard H. W. Au、Michael C. Jennings、Richard J. Puddephatt

  DOI：10.1021/om900272w

  日期：2009.7.13

  supramolecular polymers or sheet structures through hydrogen bonding. As well as the anticipated NH···O═C hydrogen bonds, some complexes formed hydrogen bonds to solvent molecules NH···O(solvent) or to coordinated bromide NH···BrPt or a combination of π-stacking with CH···Br hydrogen bonding. New forms of self-assembly in organometallic compounds were identified, one involving polymerization through

  描述了使用配体5'-[（（乙氧基羰基）氨基] -2,2'-联吡啶-5-羧酸乙酯）（1）制备有机铂（IV）配合物以形成超分子聚合物和网络材料的自组装。EtOC（＝ O）NH-氢键供体基团。配体1层发生反应以[PT 2我4（μ-SMe的2）2 ]，得到[PTME 2（1）]（2），其通过形成分子间NH ... O = C形成超分子聚合物在固体状态下氢键通过π堆积进一步自组装成片状结构。将溴甲基化合物RCH 2 Br氧化加成到络合物2中得到相应的有机铂（IV）配合物[PtBrMe 2（CH 2 R）（1）]，其中基团R可以包含另一个氢键合羧酰胺基，带有两个氢键供体基团的有机铂（IV）配合物可以通过氢键形成超分子聚合物或片状结构。除预期的NH···O═C氢键外，一些配合物还与溶剂分子NH···O（溶剂）或配位溴化物NH···BrPt或与CH·π堆积的组合形成氢键。 ··Br氢键。确定了有机金属化合
• Supramolecular organoplatinum(iv) chemistry: a nanotube structure supported by hydrogen bonds
  作者：Richard H. W. Au、Michael C. Jennings、Richard J. Puddephatt

  DOI：10.1039/b900855a

  日期：——

  BF(4) or PF(6). The complexes all take part in hydrogen bonding through either NHO[double bond]C, NHFB or NHFP interactions and, in the case with LL = 4,4'-bipyridine, X = PF(6), a supramolecular structure containing tubes is formed.

  4-BrCH（2）C（6）H（4）-C（= O）NH-t-Bu的氧化加成至[PtMe（2）（bu（2）bipy）]，bu（2）bipy = 4,4'-二叔丁基-2,2'-联吡啶，得到[PtBrMe（2）（CH（2）C（6）H（4）-C（= O）NH-t-Bu）（ bu（2）bipy）]，与AgX和桥联配体LL反应生成双核络合物[PtMe（2）（CH（2）C（6）H（4）-C（= O）NH-t- Bu）（bu（2）bipy）}（2）（mu-LL）] X（2），LL = 1,4-吡嗪或4,4'-联吡啶，X = BF（4）或PF（6） 。络合物均通过NHO [双键] C，NHFB或NHFP相互作用参与氢键，在LL = 4,4'-联吡啶，X = PF（6）的情况下，形成了包含管的超分子结构。
• Discovery of novel 5-methyl-1<i>H</i> -pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation
  作者：Daoguang Zhang、Solomon Asnake、Jingya Zhang、Per-Erik Olsson、Guisen Zhao

  DOI：10.1111/cbdd.13173

  日期：2018.6

  driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration‐resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5‐methyl‐1H‐pyrazole derivatives. AR reporter gene assay revealed compounds

  雄激素受体（AR）信号传导是前列腺癌（PCa）病情发展的核心驱动力，而且AR被证明甚至是去势抵抗性前列腺癌（CRPC）的有效治疗靶标。在此，基于两个前导化合物T3和10e通过片段剪接策略进行结构修饰，从而发现了一系列5-甲基-1 H-吡唑衍生物。AR报道基因检测表明，化合物A13和A14是有效的AR拮抗剂。该系列中的某些化合物比恩杂鲁胺更有效地抑制PCa LNCaP细胞的生长。A13和A14与人肝微粒体中的10e相比，还显示出改善的代谢稳定性。
• Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones
  作者：R HARTMANN、M REICHERT、S GOHRING

  DOI：10.1016/0223-5234(94)90104-x

  日期：——

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).