N-(2-(benzyloxy)-5-methoxybenzyl)-2-bromo-N-(2-phenoxyphenyl)acetamide | 1334484-11-5

• 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-(benzyloxy)-5-methoxybenzyl)-2-bromo-N-(2-phenoxyphenyl)acetamide
• CAS: 1334484-11-5
• 化学式: C₂₉H₂₆BrNO₄
• 分子量: 532.434
• InChiKey: LDDBMPRPSVPZLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.99
• 重原子数：
  35.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  48.0
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(2-(benzyloxy)-5-methoxybenzyl)-2-bromo-N-(2-phenoxyphenyl)acetamide 在 potassium fluoride 作用下， 以 二乙二醇 为溶剂， 反应 5.0h， 以56%的产率得到N-(2-(benzyloxy)-5-methoxybenzyl)-2-fluoro-N-(2-phenoxyphenyl)acetamide
  参考文献：
  名称：

  Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

  摘要：

  The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [F-18]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [C-11]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [C-11]PBR06 was prepared by O-[C-11]methylation of desmethyl-PBR06 with [C-11]CH3OTf in CH3CN at 80 degrees C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/mu mol specific activity at EOB. On the similar grounds, [F-18]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [F-18]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 degrees C with K[F-18]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/mu mol specific activity at EOB. Radiosynthesis of [F-18]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.06.012
• 作为产物：
  描述：

  溴甲苯 在 sodium tetrahydroborate 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 N-(2-(benzyloxy)-5-methoxybenzyl)-2-bromo-N-(2-phenoxyphenyl)acetamide
  参考文献：
  名称：

  Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

  摘要：

  The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [F-18]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [C-11]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [C-11]PBR06 was prepared by O-[C-11]methylation of desmethyl-PBR06 with [C-11]CH3OTf in CH3CN at 80 degrees C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/mu mol specific activity at EOB. On the similar grounds, [F-18]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [F-18]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 degrees C with K[F-18]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/mu mol specific activity at EOB. Radiosynthesis of [F-18]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.06.012