1-(3-三氟甲基-4-氟苯基)-2-氨基乙酮对甲苯磺酸盐 | 1082951-17-4

• 物质功能分类: 有机原料 - 氨基化合物 - 磺酸类氨基化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(3-三氟甲基-4-氟苯基)-2-氨基乙酮对甲苯磺酸盐
• 英文名称: (2-amino-1-(4-fluoro, 3-trifluoromethyl-phenyl)-ethanone) p-toluenesulfonate
• 英文别名: 2-amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone, 4-methylbenzenesulfonate；2-amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone 4-methylbenzenesulfonate；2-amino-1-(4-fluoro-3-trifluoromethyl-phenyl)-ethanone p-toluenesulfonate；2-amino-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone;4-methylbenzenesulfonic acid
• CAS: 1082951-17-4
• 化学式: C₇H₈O₃S*C₉H₇F₄NO
• 分子量: 393.359
• InChiKey: JXCIEKVLIVDZJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 海关编码：
  2922399090
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  1-(3-三氟甲基-4-氟苯基)-2-氨基乙酮对甲苯磺酸盐 在 ammonium acetate 、 1-丙基磷酸酐 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 88.5h， 生成 tert-butyl 4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g
• 作为产物：
  描述：

  4-氟-3-三氟甲基苯乙酰基溴 在 sodium azide 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 36.0h， 生成 1-(3-三氟甲基-4-氟苯基)-2-氨基乙酮对甲苯磺酸盐
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g

文献信息

• AKT AND P70 S6 KINASE INHIBITORS
  申请人：Shepherd Timothy Alan

  公开号：US20100120801A1

  公开（公告）日：2010-05-13

  The present invention provides AKT and p70 S6 kinase inhibitors of the formula: The present invention also provides pharmaceutical compositions comprising compounds of Formula I, uses of compounds of Formula I and methods of using compounds of Formula I.

  本发明提供了式子为AKT和p70 S6激酶抑制剂的药物。本发明还提供了包含式子I化合物的药物组合物，式子I化合物的用途以及使用式子I化合物的方法。
• P70 S6 KINASE INHIBITOR AND EGFR INHIBITOR COMBINATION THERAPY
  申请人：Geeganage Sandaruwan

  公开号：US20110207752A1

  公开（公告）日：2011-08-25

  The present invention provides a combination therapy comprising the compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor for use in the treatment of glioblastoma multiforme, adenocarcinomas of the colon, non-small-cell lung cancer, small-cell lung cancer, cisplatin-resistant small-cell lung cancer, ovarian cancer, leukemia, pancreatic cancer, prostate cancer, mammary carcinoma, renal cell carcimoma, multiple myeloma, Kaposis Sarcoma, Hodgkins lymphoma, lymphangioleiomyomatosis, Non-Hodgkins lymphoma or sarcoma.

  本发明提供一种联合治疗方案，包括化合物4-[4-[4-(4-氟-3-三氟甲基苯基)-1-甲基-1H-咪唑-2-基]-哌啶-1-基]-1H-吡唑并[3,4-d]嘧啶，或其药学上可接受的盐，以及一种EGFR抑制剂，用于治疗脑胶质母细胞瘤、结肠腺癌、非小细胞肺癌、小细胞肺癌、顺铂耐药小细胞肺癌、卵巢癌、白血病、胰腺癌、前列腺癌、乳腺癌、肾细胞癌、多发性骨髓瘤、卡波西肉瘤、霍奇金淋巴瘤、淋巴管平滑肌瘤病、非霍奇金淋巴瘤或肉瘤的治疗。
• P70 S6 KINASE INHIBITORS
  申请人：Dally Robert Dean

  公开号：US20120071490A1

  公开（公告）日：2012-03-22

  The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.

  本发明提供了公式为：p70 S6激酶抑制剂的制剂，以及包含它们的药物制剂和使用它们的方法。
• P70 S6 KINASE INHIBITOR AND MTOR INHIBITOR COMBINATION THERAPY
  申请人：Geeganage Sandaruwan

  公开号：US20110212977A1

  公开（公告）日：2011-09-01

  The present invention provides a combination therapy comprising the compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine, or a pharmaceutically acceptable salt thereof, and an mTOR inhibitor for use in the treatment of glioblastoma multiforme, adenocarcinomas of the colon, non-small-cell lung cancer, small-cell lung cancer, cisplatin-resistant small-cell lung cancer, ovarian cancer, leukemia, pancreatic cancer, prostate cancer, mammary carcinoma, renal cell carcimoma, multiple myeloma, Kaposis Sarcoma, Hodgkins lymphoma, lymphangioleiomyomatosis, Non-Hodgkins lymphoma or sarcoma.

  本发明提供了一种组合疗法，包括化合物4-[4-[4-(4-氟-3-三氟甲基-苯基)-1-甲基-1H-咪唑-2-基]-哌啶-1-基]-1H-吡唑并[3,4-d]嘧啶或其药学上可接受的盐，以及mTOR抑制剂，用于治疗胶质母细胞瘤、结肠腺癌、非小细胞肺癌、小细胞肺癌、顺铂耐药小细胞肺癌、卵巢癌、白血病、胰腺癌、前列腺癌、乳腺癌、肾细胞癌、多发性骨髓瘤、卡波西肉瘤、霍奇金淋巴瘤、淋巴管平滑肌瘤病、非霍奇金淋巴瘤或肉瘤的治疗。
• WO2008/140947
  申请人：——

  公开号：——

  公开（公告）日：——