4-((4-氨基-3-氯苯基)硫代)苯甲腈 | 1360607-85-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 4-((4-氨基-3-氯苯基)硫代)苯甲腈
• 英文名称: 4-((4-Amino-3-chlorophenyl)thio)benzonitrile
• 英文别名: 4-(4-amino-3-chlorophenyl)sulfanylbenzonitrile
• CAS: 1360607-85-7
• 化学式: C₁₃H₉ClN₂S
• 分子量: 260.747
• InChiKey: FKQDYZCSJXYPHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  483.4±45.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((4-氨基-3-氯苯基)硫代)苯甲腈 在 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 20.5h， 生成 4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)thio)N,N-dimethylbenzamide
  参考文献：
  名称：

  PDK抑制剂AZD7545的工艺开发和规模扩大

  摘要：

  简要比较了AZD7545的早期制造路线。详细报告了首选长期制造路线的工艺开发，并讨论了从最初的公斤级路线开始的变化。在每个阶段的讨论中都包含了中试工厂生产的放大经验。AZD7545整个开发过程中值得注意的方面涉及化学危害，机理，分析和杂质，本案例研究将重点关注这些方面。

  DOI：

  10.1021/op2003419
• 作为产物：
  描述：

  2-氯-4-硫代氰酰基苯胺 在 copper(I) oxide 、 sodiumsulfide nonahydrate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-((4-氨基-3-氯苯基)硫代)苯甲腈
  参考文献：
  名称：

  Kepner-Tregoe Decision Analysis as a Tool To Aid Route Selection. Part 2. Application to AZD7545, a PDK Inhibitor

  摘要：

  Kepner-Tregoe decision analysis was formally used as an aid to route selection, as outlined in the preceding paper. Over 40 paper routes were assessed for suitability for both immediate and longer term manufacture of AZD7545, a compound in the early stages of development. Eight routes were then investigated in fall in the laboratory, and a further four in part, over a period of 3-4 months. From this exercise, the preferred long-term manufacturing route was identified before the first pilot scale manufacture had been completed. This route selection exercise worked well in this case where a large number of potential routes had to be considered using limited resources. It was also an effective means of bringing some long-term manufacturing issues to the fore at an early stage in development.

  DOI：

  10.1021/op800033c

文献信息

• Assembly of (hetero)aryl thioethers <i>via</i> simple nucleophilic aromatic substitution and Cu-catalyzed coupling reactions with (hetero)aryl chlorides and bromides under mild conditions
  作者：Weiqi Liu、Xinghao Jin、Dawei Ma

  DOI：10.1039/d3gc02066e

  日期：——

  requirement of higher reaction temperatures for an SNAr reaction between thiols and less reactive electron-poor aryl halides described in earlier reports has triggered intensive studies on the development of metal- and photo-catalyzed methods to promote this transformation. We report here that an SNAr reaction of thiols with most electron-poor aryl halides takes place at RT–60 °C under the action of

  早期报道中描述的硫醇和反应性较低的缺电子芳基卤化物之间的S N Ar 反应需要更高的反应温度，这引发了对开发金属和光催化方法以促进这种转变的深入研究。我们在此报告，在 K 2 CO 3和 DMAc的作用下，硫醇与大多数缺电子芳基卤化物在 RT–60 °C 下发生S N Ar 反应。在这种温和的条件下，碱和溶剂都起着至关重要的作用。对于对 S N不发生反应的（杂）芳基卤化物Ar反应中，鉴定出两种更强大的草酸二酰胺配体，使其Cu催化的偶联反应能够在低催化负载量下进行。这两种方法的结合为制备（杂）芳基硫醚提供了一种非常有吸引力的方法。
• Kepner-Tregoe Decision Analysis as a Tool To Aid Route Selection. Part 2. Application to AZD7545, a PDK Inhibitor
  作者：Jonathan D. Moseley、David Brown、Catherine R. Firkin、Shelley L. Jenkin、Bharti Patel、Evan W. Snape

  DOI：10.1021/op800033c

  日期：2008.11.21

  Kepner-Tregoe decision analysis was formally used as an aid to route selection, as outlined in the preceding paper. Over 40 paper routes were assessed for suitability for both immediate and longer term manufacture of AZD7545, a compound in the early stages of development. Eight routes were then investigated in fall in the laboratory, and a further four in part, over a period of 3-4 months. From this exercise, the preferred long-term manufacturing route was identified before the first pilot scale manufacture had been completed. This route selection exercise worked well in this case where a large number of potential routes had to be considered using limited resources. It was also an effective means of bringing some long-term manufacturing issues to the fore at an early stage in development.
• Process Development and Scale-Up of AZD7545, a PDK Inhibitor
  作者：Bharti Patel、Catherine R. Firkin、Evan W. Snape、Shelley L. Jenkin、David Brown、Julian G. K. Chaffey、Philip A. Hopes、Carl D. Reens、Mike Butters、Jonathan D. Moseley

  DOI：10.1021/op2003419

  日期：2012.3.16

  manufacturing routes to AZD7545 is given. Process development of the preferred long-term manufacturing route is reported in detail, and changes from the initial kilogram-scale route are discussed. Scale-up experience from the pilot-plant manufacture is included in the discussion of each stage. Noteworthy aspects throughout the development of AZD7545 concerned chemical hazards, mechanisms, analysis, and impurities

  简要比较了AZD7545的早期制造路线。详细报告了首选长期制造路线的工艺开发，并讨论了从最初的公斤级路线开始的变化。在每个阶段的讨论中都包含了中试工厂生产的放大经验。AZD7545整个开发过程中值得注意的方面涉及化学危害，机理，分析和杂质，本案例研究将重点关注这些方面。