methyl 3-((4-fluorophenyl)thio)-2-hydroxy-2-methylpropanoate | 1098651-01-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: methyl 3-((4-fluorophenyl)thio)-2-hydroxy-2-methylpropanoate
• 英文别名: Methyl 2-hydroxy-2-methyl-3-(4-fluorophenylthio)-propionate；methyl 3-(4-fluorophenyl)sulfanyl-2-hydroxy-2-methylpropanoate
• CAS: 1098651-01-4
• 化学式: C₁₁H₁₃FO₃S
• 分子量: 244.287
• InChiKey: ADWWGHQIQLUIHA-UHFFFAOYSA-N

物化性质

• 沸点：
  354.1±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-((4-fluorophenyl)thio)-2-hydroxy-2-methylpropanoate 在 水 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 sodium hydroxide 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 生成 2-[3-(4-Chlorophenyl)-1,2,4-oxadiazol-5-yl]-1-(4-fluorophenyl)sulfanylpropan-2-ol
  参考文献：
  名称：

  1,2,4-Oxadiazoles: A new class of anti-prostate cancer agents

  摘要：

  Sulfide and sulfonyl derivatives of 1,2,4-oxadiazoles were synthesized and screened by MTT assay on the prostate cancer cells, DU-145. Six compounds were identified as potential anti-prostate cancer agents with IC50 values ranging from 0.5 to 5.1 mu M. These compounds exhibited good activity on the androgen independent cells PC-3, while the results were moderate on androgen dependent LNCaP cells, suggesting the possibility of a mechanism of action different from that of the bioisosteric bicalutamide. Also a very low cytotoxicity was observed on non-cancerous cells MCF-10A. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.059
• 作为产物：
  描述：

  甲基丙烯酸甲酯 在 Oxone 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 生成 methyl 3-((4-fluorophenyl)thio)-2-hydroxy-2-methylpropanoate
  参考文献：
  名称：

  1,2,4-Oxadiazoles: A new class of anti-prostate cancer agents

  摘要：

  Sulfide and sulfonyl derivatives of 1,2,4-oxadiazoles were synthesized and screened by MTT assay on the prostate cancer cells, DU-145. Six compounds were identified as potential anti-prostate cancer agents with IC50 values ranging from 0.5 to 5.1 mu M. These compounds exhibited good activity on the androgen independent cells PC-3, while the results were moderate on androgen dependent LNCaP cells, suggesting the possibility of a mechanism of action different from that of the bioisosteric bicalutamide. Also a very low cytotoxicity was observed on non-cancerous cells MCF-10A. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.059

文献信息

• Auto-oxidative hydroxysulfenylation of alkenes
  作者：Congde Huo、Yajun Wang、Yong Yuan、Fengjuan Chen、Jing Tang

  DOI：10.1039/c6cc01937d

  日期：——

  One-pot auto-oxidation mediated hydroxysulfenylation of electron-deficient and electron-rich olefins with phenthiols was explored.

  一锅法介导的电子不足和电子富集烯烃与苯硫醇的羟基硫醚化反应被探索。
• Hydroxysulfenylation of Electron-Deficient Alkenes through an Aerobic Copper Catalysis
  作者：Hui Xi、Bicheng Deng、Zhenzhen Zong、Shenglin Lu、Zhiping Li

  DOI：10.1021/acs.orglett.5b00112

  日期：2015.3.6

  A copper-catalyzed hydroxysulfenylation of α,β-unsaturated esters/amides is reported. The method presents a selective and efficient synthesis of β-hydroxysulfides bearing electron-withdrawing groups. The synthetic utility of this method is demonstrated by the concise synthesis of the anticancer drug bicalutamide.

  据报道，铜催化的α，β-不饱和酯/酰胺的羟基亚磺酰基化。该方法提出了具有吸电子基团的β-羟基硫化物的选择性和有效的合成。该方法的合成效用通过抗癌药物比卡鲁胺的简明合成得到证明。
• Procedure for the synthesis of bicalutamide
  申请人：Pizzatti Enrica

  公开号：US20060041161A1

  公开（公告）日：2006-02-23

  The object of the invention is an improved procedure for the synthesis of bicalutamide, characterised in that the 2-hydroxy-2-methyl-3-(4-fluorophenylthio) propionic acid initially produced undergoes a step to acylate the hydroxyl group in position 2 to give an intermediate 2-acyloxy-2-methyl-3-(4-fluorophenylthio) propionic acid, which allows the formation of a successive N-[4-cyano-3-(trifluoromethyl)-phenyl-]-3-[4-fluorophenylthio]-2-acyloxy-2-methyl-propionamide intermediate.

  该发明的对象是一种改进的比卡鲁胺合成方法，其特征在于最初生成的2-羟基-2-甲基-3-(4-氟苯硫基)丙酸经历一步酰化羟基在2位的过程，得到一个中间体2-酰氧基-2-甲基-3-(4-氟苯硫基)丙酸，这允许形成一个连续的N-[4-氰基-3-(三氟甲基)苯基]-3-[4-氟苯硫基]-2-酰氧基-2-甲基-丙酰胺中间体。
• Novel process for preparing rac-bicalutamide and its intermediates
  申请人：——

  公开号：US20030045741A1

  公开（公告）日：2003-03-06

  The present invention relates to a new process for the synthesis of racemic and optically active bicalutamide starting from ethyl pyruvate and methyl methacrylate. The present invention discloses processes of preparing bicalutamide intermediates including ethyl-[2-{4-fluorophenyl sulfone}]-2-hydroxy propionate, 1,2-epoxy-2-methyl propionate and 2-hydrox-2-methyl-3-(4-fluorophenylthio)propionic acid. The present invention further discloses micronized rac-bicalutamide and the preparation thereof.

  本发明涉及一种从乙酰丙酸乙酯和甲基丙烯酸甲酯合成外消旋和光学活性比卡鲁胺的新工艺。本发明揭示了制备比卡鲁胺中间体的过程，包括乙基-[2-{4-氟苯砜}]-2-羟基丙酸酯、1,2-环氧-2-甲基丙酸酯和2-羟基-2-甲基-3-(4-氟苯硫)丙酸。本发明还揭示了微粉化的外消旋比卡鲁胺及其制备方法。
• Novel process for preparing and isolating rac-bicalutamide and its intermediates
  申请人：——

  公开号：US20040044249A1

  公开（公告）日：2004-03-04

  The present invention relates to a new process for the synthesis of racemic and optically active bicalutamide starting from ethyl pyruvate and methyl methacrylate. The present invention discloses processes of preparing bicalutamide intermediates including ethyl-[2-{4-fluorophenyl sulfone}]-2-hydroxy propionate, 1,2-epoxy-2-methyl propionate and 2-hydrox-2-methyl-3-(4-fluorophenylthio) propionic acid. The present invention further discloses micronized rac-bicalutamide and the preparation thereof. The present invention further discloses a new process for the isolation and purification of racemic and optically active bicalutamide.

  该发明涉及一种从乙酸乙酯和甲基丙烯酸甲酯合成外消旋和光学活性比卡鲁胺的新工艺。该发明揭示了制备比卡鲁胺中间体的过程，包括乙基-[2-4-氟苯基砜}-2-羟基丙酸酯、1,2-环氧-2-甲基丙酸酯和2-羟基-2-甲基-3-(4-氟苯硫基)丙酸。该发明还揭示了微粉化的外消旋比卡鲁胺及其制备方法。该发明还揭示了一种新的分离和纯化外消旋和光学活性比卡鲁胺的工艺。