4-(3-(bromodifluoromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide | 929030-64-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-(bromodifluoromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide
• 英文别名: 4-[3-(bromodifluoromethyl)-5-p-tolylpyrazol-1-yl]-benzenesulfonamide
• CAS: 929030-64-8
• 化学式: C₁₇H₁₄BrF₂N₃O₂S
• 分子量: 442.284
• InChiKey: HOUCIZNBKDPBNK-UHFFFAOYSA-N

物化性质

• 熔点：
  184-185 °C
• 沸点：
  564.2±60.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.94
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.98
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(3-(bromodifluoromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 1.75h， 生成 塞来西布
  参考文献：
  名称：

  Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression

  摘要：

  Synthesis of [F-18]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([F-18]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [F-18]F- exchange reaction. Synthesis of the precursor for radiolabeling was achieved from 4'-methylacetophenone in four steps with 22% overall yield. Under non-radioactive conditions, fluorination was achieved using TBAF in DMSO at 135 degrees C in 80% yield. Synthesis of [F-18]celecoxib was achieved using [F-18]TBAF in DMSO at 135 degrees C in 10 +/- 2% yield (EOS) with > 99% chemical and radiochemical purities. The specific activity was 120 +/- 40 mCi/mu mol (EOB). [F-18]celecoxib was found to be stable in ethanol, however, de[F-18]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[F-18]fluorination of [F-18]celecoxib. PET studies in baboon indicated a lower rate of de[F-18]fluorination than rat and retention of radioactivity in brain regions consistent with the known distribution of COX-2. A radiolabeling method that can generate consistent high specific activity is needed for routine human use. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.033
• 作为产物：
  描述：

  4-bromo-4,4-difluoro-1-p-tolylbutane-1,3-dione 、 4-肼基苯磺酰胺 以 乙醇 为溶剂， 反应 16.0h， 以45%的产率得到4-(3-(bromodifluoromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide
  参考文献：
  名称：

  Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression

  摘要：

  Synthesis of [F-18]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([F-18]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [F-18]F- exchange reaction. Synthesis of the precursor for radiolabeling was achieved from 4'-methylacetophenone in four steps with 22% overall yield. Under non-radioactive conditions, fluorination was achieved using TBAF in DMSO at 135 degrees C in 80% yield. Synthesis of [F-18]celecoxib was achieved using [F-18]TBAF in DMSO at 135 degrees C in 10 +/- 2% yield (EOS) with > 99% chemical and radiochemical purities. The specific activity was 120 +/- 40 mCi/mu mol (EOB). [F-18]celecoxib was found to be stable in ethanol, however, de[F-18]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[F-18]fluorination of [F-18]celecoxib. PET studies in baboon indicated a lower rate of de[F-18]fluorination than rat and retention of radioactivity in brain regions consistent with the known distribution of COX-2. A radiolabeling method that can generate consistent high specific activity is needed for routine human use. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.033

文献信息

• Synthesis of bromodifluoromethyl substituted pyrazoles and isoxazoles
  作者：Xueyan Yang、Shengxia Shui、Xi Chen、Hai’ou He、Fanhong Wu

  DOI：10.1016/j.jfluchem.2009.12.017

  日期：2010.3

  Bromodifluoromethyl substituted β-diketone 3a–3d, prepared from corresponding ketones and ethyl bromodifluoroactate in the presence of sodium methoxide, reacted with aryl hydrazine derivatives affording bromodifluoromethyl substituted pyrazoles in high regioselectivity. The reaction of 3a–3d with hydroxylamine hydrochloride gave dihydroisoxazoles, which afforded bromodifluoromethyl substituted isoxazoles through

  溴二氟甲基取代的β-二酮3a-3d，是由相应的酮和溴二氟乙酸乙酯在甲醇钠存在下制得的，与芳基肼衍生物反应，得到具有高区域选择性的溴二氟甲基取代的吡唑。3a–3d与羟胺盐酸盐的反应生成二氢异恶唑，后者通过PPA或浓硫酸脱水而制得溴二氟甲基取代的异恶唑。