N-(2-fluorophenyl)-3,4-dimethoxythiobenzamide | 872726-67-5

• 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: N-(2-fluorophenyl)-3,4-dimethoxythiobenzamide
• 英文别名: N-(2-fluorophenyl)-3,4-dimethoxybenzenecarbothioamide
• CAS: 872726-67-5
• 化学式: C₁₅H₁₄FNO₂S
• 分子量: 291.346
• InChiKey: XLLVGGRQYQBXMP-UHFFFAOYSA-N

物化性质

• 沸点：
  389.5±52.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-fluorophenyl)-3,4-dimethoxythiobenzamide 在 2,2,6,6-四甲基哌啶氧化物 作用下， 以 氯仿 为溶剂， 反应 12.0h， 以68%的产率得到2-(3,4-二甲氧基苯基)-4-氟苯并噻唑
  参考文献：
  名称：

  外源光敏剂，无金属和无碱可见光通过逆向氢原子转移促进了C–H硫醇化

  摘要：

  无需添加光敏剂，金属催化剂或碱即可实现可见光驱动的分子内C（sp 2）–H硫醇化。该反应诱导了硫代苯甲酰胺环化为苯并噻唑。底物吸收可见光，并且其激发态与2,2,6,6-四甲基哌啶N-氧基发生反向氢原子转移（RHAT），形成硫自由基。硫自由基加到苯环上会得到一个芳基，然后再通过RHAT重新形成苯并噻唑。

  DOI：

  10.1021/acs.orglett.8b03679
• 作为产物：
  描述：

  2-氟苯胺 在 劳森试剂 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.0h， 生成 N-(2-fluorophenyl)-3,4-dimethoxythiobenzamide
  参考文献：
  名称：

  外源光敏剂，无金属和无碱可见光通过逆向氢原子转移促进了C–H硫醇化

  摘要：

  无需添加光敏剂，金属催化剂或碱即可实现可见光驱动的分子内C（sp 2）–H硫醇化。该反应诱导了硫代苯甲酰胺环化为苯并噻唑。底物吸收可见光，并且其激发态与2,2,6,6-四甲基哌啶N-氧基发生反向氢原子转移（RHAT），形成硫自由基。硫自由基加到苯环上会得到一个芳基，然后再通过RHAT重新形成苯并噻唑。

  DOI：

  10.1021/acs.orglett.8b03679

文献信息

• Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents
  作者：Min Wang、Mingzhang Gao、Bruce H. Mock、Kathy D. Miller、George W. Sledge、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1016/j.bmc.2006.08.026

  日期：2006.12

  benzyl ether group of compound 6a using H(2)/Pd-C provided the precursor 4-fluoro-2-(3-hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of radiolabeling precursors and the reference standards 5- and 6-fluorinated arylbenzothiazoles (11c-n) was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. The target radiotracers carbon-11

  氟化的2-芳基苯并噻唑是新的潜在抗肿瘤药物，对乳腺癌，肺癌和结肠癌细胞系表现出有效的选择性抑制活性。碳11标记的氟化2-芳基苯并噻唑可作为正电子发射断层扫描（PET）成像癌症中酪氨酸激酶的新型探针。通过以下方法制备4-氟代2-芳基苯并噻唑4-氟-2-（3-苄氧基-4-甲氧基苯基）苯并噻唑（6a）和4-氟-2-（3,4-二甲氧基苯基）苯并噻唑（6b） Jacobson硫代苯胺基自由基环化化学的修饰。使用H（2）/ Pd-C对化合物6a的苄基醚基进行氢解裂解，可提供用于放射性标记的前体4-氟-2-（3-羟基-4-甲氧基苯基）苯并噻唑（7）。通过在还原条件下使邻氨基硫酚二硫化物与取代的苯甲醛反应，可以合成放射性标记的前体和参考标准的5和6氟代芳基苯并噻唑（11c-n）。目标放射性示踪剂碳11标记为4-，5-和6-氟化的芳基苯并噻唑（3-[（11）C] 6b，4-[（11）C] 11c，3-[（11）C]
• 2-Arylbenzothiazole derivatives
  申请人：Stevens Francis G. Malcolm

  公开号：US20060063816A1

  公开（公告）日：2006-03-23

  A compound of general structure I, wherein the compound is optionally in the form of an N-oxide or S-oxide or prodrug form and/or pharmaceutically acceptable salt thereof wherein: each of R 1 to R 9 is independently selected from hydrogen, hydroxyl, alkoxy, halo, mesyl, CX 3 (X=halo), —O(CH 2 )nNYZ—, substituted or unsubstituted lower alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; optionally R 6 and R 7 together form a dioxymethylene (—OCH 2 O—) unit and wherein n is 1 to 3 and Y and Z are independently selected from any of the following: C 1 -C 6 straight chain, branched or cyclic substituted or unsubstituted alkyl group, Y and Z can be taken together to form a cyclic alkyl or hetereoalkyl group wherein in addition to N the hetereoalkyl group comprises a heteroatom selected from N, O or S.

  通用结构I的化合物，其中该化合物可以是N-氧化物或S-氧化物或前药形式和/或其药用可接受盐形式，其中：R1至R9中的每一个独立地选择自氢、羟基、烷氧基、卤素、甲磺基、CX3（X=卤素）、—O(CH2)nNYZ—、取代或未取代的较低烷基、取代或未取代的杂烷基、取代或未取代的芳基或杂芳基，以及取代或未取代的芳基或杂芳基；可选地，R6和R7一起形成二氧亚甲基（—OCH2O—）单元，其中n为1至3，Y和Z分别选择自以下任一：C1-C6直链、支链或环状取代或未取代的烷基，Y和Z可以一起形成环状烷基或杂环烷基，其中除N外，杂环烷基还包括从N、O或S中选择的杂原子。
• 2-arylbenzothiazole derivatives
  申请人：Pharminxo Limited

  公开号：US07384966B2

  公开（公告）日：2008-06-10

  A compound of general structure I, wherein the compound is optionally in the form of an N-oxide or S-oxide or prodrug form and/or pharmaceutically acceptable salt thereof wherein: each of R1 to R9 is independently selected from hydrogen, hydroxyl, alkoxy, halo, mesyl, CX3 (X=halo), —O(CH2)nNYZ-, substituted or unsubstituted lower alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; optionally R6 and R7 together form a dioxymethylene (—OCH2O—) unit and wherein n is 1 to 3 and Y and Z are independently selected from any of the following: C1-C6 straight chain, branched or cyclic substituted or unsubstituted alkyl group, Y and Z can be taken together to form a cyclic alkyl or hetereoalkyl group wherein in addition to N the hetereoalkyl group comprises a heteroatom selected from N, O or S.

  一种一般结构为I的化合物，其中该化合物可选为N-氧化物或S-氧化物或前药形式和/或其药学上可接受的盐，其中： R1到R9中的每个独立地选择自氢、羟基、烷氧基、卤素、甲烷基磺酰基、CX3（X=卤素）、—O(CH2)nNYZ-、取代或未取代的低烷基、取代或未取代的杂烷基、取代或未取代的芳基或杂芳基、和取代或未取代的芳基烷基或杂芳基烷基；可选地，R6和R7一起形成二氧甲基（—OCH2O—）单元；其中n为1到3，Y和Z独立选择自以下任一：C1-C6直链、支链或环状取代或未取代的烷基，Y和Z可一起形成环状烷基或杂环烷基，其中除N外，杂环烷基包括从N、O或S选择的杂原子。
• Antitumor Benzothiazoles. 26. 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a Simple Fluorinated 2-Arylbenzothiazole, Shows Potent and Selective Inhibitory Activity against Lung, Colon, and Breast Cancer Cell Lines
  作者：Catriona G. Mortimer、Geoffrey Wells、Jean-Philippe Crochard、Erica L. Stone、Tracey D. Bradshaw、Malcolm F. G. Stevens、Andrew D. Westwell

  DOI：10.1021/jm050942k

  日期：2006.1.1

  A series of new 2-phenylbenzothiazoles has been synthesized on the basis of the discovery of the potent and selective in vitro antitumor properties of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (8n; GW 610. NSC 721648). Synthesis of analogues substituted in the benzothiazole ring was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. Compounds were evaluated in vitro in four human cancer cell lines, and compound 8n was found to possess exquisitely potent antiproliferative activity (GI(50) < 0.1 nM for MCF-7 and MDA 468). Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. Structure-activity relationships established that the compound 8n stands on a pinnacle of potent activity, with most structural variations having a deactivating in vitro effect. Mechanistically, this new series of agents contrasts with the previously reported 2-(4-aminophenyl)benzothiazoles; compound 8n is not reliant on induction of CYP1A1 expression for antitumor activity.
• External Oxidant-Free Oxidative Cross-Coupling: A Photoredox Cobalt-Catalyzed Aromatic C–H Thiolation for Constructing C–S Bonds
  作者：Guoting Zhang、Chao Liu、Hong Yi、Qingyuan Meng、Changliang Bian、Hong Chen、Jing-Xin Jian、Li-Zhu Wu、Aiwen Lei

  DOI：10.1021/jacs.5b05665

  日期：2015.7.29

  An external oxidant-free oxidative coupling for aromatic C-H thiolation by visible-light photoredox cobalt-catalysis has been developed. Various substrates could afford benzothiazoles in good to excellent yields, and only H2 is generated as a side product. When catalytic TBAOH was used as the base, not only 2-aryl but also 2-alkylbenzothiazoles could be obtained through this novel dehydrogenative coupling reaction. This method could be scaled up and applied to the synthesis of biologically active molecules bearing benzothiazole structural scaffolds (potent antitumor agents). Furthermore, the unexpected oxidation byproduct amides, which are often generated in oxidative cyclization of thiobenzanilides, can be completely avoided. Mechanistic studies showed that the H2 originates from the substrates. The kinetic studies indicate that the interaction between the cobalt catalyst and proton might be involved in the rate-limiting process.