3-amino-5-phenylisothiazole-4-carbonitrile | 20943-38-8

• 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: 3-amino-5-phenylisothiazole-4-carbonitrile
• 英文别名: 3-Amino-5-phenyl-4-isothiazolcarbonitril；3-Amino-5-phenyl-1,2-thiazole-4-carbonitrile
• CAS: 20943-38-8
• 化学式: C₁₀H₇N₃S
• 分子量: 201.252
• InChiKey: QTFQLNSIGFJXIN-UHFFFAOYSA-N

物化性质

• 熔点：
  127-128 °C(Solv: cyclohexane (110-82-7))
• 沸点：
  336.3±42.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-5-phenylisothiazole-4-carbonitrile 在 肼 作用下， 反应 0.33h， 以93%的产率得到3-氨基-5-苯基-1H-吡唑-4-甲腈
  参考文献：
  名称：

  The conversion of isothiazoles into pyrazoles using hydrazine

  摘要：

  The conversion of isothiazoles into pyrazoles on treatment with hydrazine is investigated. The influence of various C-3, C-4 and C-5 isothiazole substituents and some limitations of this ring transformation are examined. When the isothiazole C-3 substituent is a good nucleofuge, 3-aminopyrazoles are obtained. However, when the 3-substituent is not a leaving group it is retained in the pyrazole product. Treatment of 4-bromo-3-chloro-5-phenylisothiazoie 56 or 3-chloro-4,5-diphenylisothiazole 57 with anhydrous hydrazine at ca. 200 degrees C for a few minutes gives the corresponding 3-hydrazinoisothiazoles 61 and 64 respectively in high yields; the stability of these new hydrazines is investigated. 5,5'-Diphenyl-3,3'-biisothiazole-4,4'-dicarbonitrile 78 reacts with hydrazine to give 5,5'-diphenyl-3,3'-bi(1H-pyi-azole)-4,4'-dicarbonitrile 79. Methylhydrazine reacts with 3-chloro-5-phenytisothiazole-4-carbonitrile 1 to give 3-(1-methylhydrazino)-5-phenylisothiazole-4-carbontrile 83 and 3-amino-lmethyl-5-phenylpyrazole-4-carbonitrile 84. All products are fully characterised and rational mechanisms for the isothiazole into pyrazole transformation are proposed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.06.041
• 作为产物：
  描述：

  phenyl-thioxo-succinonitrile; sodium enethiolate 在 氯胺 作用下， 生成 3-amino-5-phenylisothiazole-4-carbonitrile
  参考文献：
  名称：

  Hartke,K.; Peshkar,L., Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft, 1968, vol. 301, # 8, p. 611 - 621

  摘要：

  DOI：

文献信息

• New regiospecific isothiazole C–C coupling chemistry
  作者：Irene C. Christoforou、Panayiotis A. Koutentis

  DOI：10.1039/b607442a

  日期：——

  Regioselective palladium catalysed coupling reactions are achieved in good to high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4-carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and alkynyl)isothiazoles 3, 4, 6–9 from Stille couplings, 3-halo-5-(hetero/arylethynyl)isothiazoles 14–19 from Sonogashira and 5,5′-bi(3-chloroisothiazole-4-carbonitrile) (13) from an Ullmann type coupling. 3,5-Dibromoisothiazole-4-carbonitrile 2 is more reactive than the dichloroisothiazole-4-carbonitrile 1 and effective enough for Stille, Negishi and Sonogashira couplings. 5,5-Bi(3-chloroisothiazole-4-carbonitrile) (13) is prepared by a palladium catalysed Ullmann coupling from 3-chloro-5-iodoisothiazole-4-carbonitrile (11). A variety of 3-substituted isothiazoles (3-substituents = Cl, Br, OMs, OTs and OTf) are less reactive and fail to give successful Suzuki couplings at the isothiazole C-3 position. The 3-iodo-5-phenyl-isothiazole-4-carbonitrile (28), prepared via Sandmeyer iodination, participates successfully in Suzuki, Ullmann type, Stille, Negishi and Sonogashira coupling reactions. All products are fully characterized.

  区域选择性钯催化的偶联反应以良好至高产率实现，从3,5-二氯或3,5-二溴异噻唑-4-腈1和2出发，通过Stille偶联反应得到3-卤代-5-(杂/芳基、烯基和炔基)异噻唑3、4、6–9，通过Sonogashira反应得到3-卤代-5-(杂/芳基炔基)异噻唑14–19，以及通过Ullmann型偶联反应得到5,5'-二(3-氯异噻唑-4-腈)13。3,5-二溴异噻唑-4-腈2比3,5-二氯异噻唑-4-腈1更具反应活性，足以有效进行Stille、Negishi和Sonogashira偶联反应。5,5-二(3-氯异噻唑-4-腈)13通过钯催化的Ullmann偶联反应由3-氯-5-碘异噻唑-4-腈11制备。多种3-取代异噻唑（3-取代基=Cl、Br、OMs、OTs和OTf）反应活性较低，未能成功在异噻唑C-3位置进行Suzuki偶联反应。通过Sandmeyer碘化法制备的3-碘-5-苯基异噻唑-4-腈28成功参与了Suzuki、Ullmann型、Stille、Negishi和Sonogashira偶联反应。所有产物均经过充分表征。
• Methods of Treatment of Amyloidosis Using Subsituted Ethanolcyclicamine Aspartyl Protease Inhibitors
  申请人：Hom Roy

  公开号：US20080166332A1

  公开（公告）日：2008-07-10

  The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein

  这项发明涉及新型化合物和治疗与淀粉样蛋白病相关的疾病、紊乱和症状的方法。淀粉样蛋白病是指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和症状。
• Oxime derivative substituted hydroxyethylamine aspartyl protease inhibitors
  申请人：John Varghese

  公开号：US20060135581A1

  公开（公告）日：2006-06-22

  The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

  该发明涉及新型化合物和治疗与淀粉样变性相关的疾病、疾病和病情的方法。淀粉样变性是指与A-beta蛋白的异常沉积相关的一系列疾病、疾病和病情的集合。
• OXIME DERIVATIVE SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
  申请人：John Varghese

  公开号：US20090042961A1

  公开（公告）日：2009-02-12

  The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

  该发明涉及新型化合物和治疗与淀粉样变性相关的疾病、障碍和病状的方法。淀粉样变性是指与A-beta蛋白异常沉积相关的一组疾病、障碍和病状。
• 3-PHENYL-5-UREIDOISOTHIAZOLE-4-CARBOXIMIDE AND 3-AMINO-5-PHENYLISOTHIAZOLE DERIVATIVES AS KINASE INHIBITORS
  申请人：Allergan, Inc.

  公开号：US20130172353A1

  公开（公告）日：2013-07-04

  This invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein R, R 1 , R 2 , R 3 , n, X 1 , X 2 , L 1 , and L 2 are as defined herein. The compounds of Formula I are useful as receptor tyrosine kinase (RTK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders and metabolic diseases.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R、R1、R2、R3、n、X1、X2、L1和L2的定义如本文所述。公式I的化合物可用作受体酪氨酸激酶（RTK）抑制剂，并可用于治疗癌症、血管增殖性疾病、纤维性疾病、系膜细胞增殖性疾病和代谢性疾病。