2-((tert-butyldimethylsilyl)ethynyl)-6-fluoropyridine | 1391741-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-((tert-butyldimethylsilyl)ethynyl)-6-fluoropyridine
• CAS: 1391741-63-1
• 化学式: C₁₃H₁₈FNSi
• 分子量: 235.377
• InChiKey: AJBXULMCJIMCQC-UHFFFAOYSA-N

物化性质

• 沸点：
  275.0±40.0 °C(predicted)
• 密度：
  0.98±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  16.0
• 可旋转键数：
  0.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  12.89
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  2-((tert-butyldimethylsilyl)ethynyl)-6-fluoropyridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 2-乙炔基-6-氟吡啶
  参考文献：
  名称：

  Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

  摘要：

  Solid tumors often develop an acidic microenvironment, which plays a critical role in tumor progression and is associated with increased level of invasion and metastasis. The 37 residue pH (low) insertion peptide (pHLIP) is under study as an imaging platform because of its Unique ability to insert into cell membranes at a low extracellular pH (pH(e) < 7). Labeling of peptides with [F-18] fluorine is usually performed via prosthetic groups using chemoselective coupling reactions. One of the most successful procedures involves the alkyne-azide copper(I) catalyzed cydoaddition (CuAAC). However, none of the known "click" methods have been applied to peptides as large as pHLIP. We designed a novel prosthetic group and extended the use of the CuAAC "click chemistry" for the simple and efficient F-18 labeling of large peptides. For the evaluation of this labeling approach, a D-amino acid analogue of WT-pHLIP and an L-amino acid control peptide K-pHLIP, both functionalized at the N-terminus with 6-azidohexanoic acid, were used. The novel 6-[F-18]fluoro-2-ethynylpyridine prosthetic group, was obtained via nucleophilic substitution on the corresponding bromo-precursor after 10 mm at 130 C with a radiochemical yield of 27.5 +/- 6.6% (decay corrected) with high radiochemical purity >= 98%. The subsequent Cu-I-catalyzed "click" reaction with the azido functionalized pHLIP peptides was quantitative within 5 min at 70 C in a mixture of water and ethanol using Cu acetate and sodium L-ascorbate. j D-WT-pHLIP and [F-18]-L-K-pHLIP were obtained with total radiochemical yields of 5-20% after HPLC purification. The total reaction time was 85 min including formulation. In vitro stability tests revealed high stability of the [F-18]-6-WT-pHLIP in human and mouse plasma after 120 mm, with the parent tracer remaining intact at 65% and 85%, respectively. PET imaging and biodistribution studies in LNCaP and PC -3 xenografted mice with the [F-18]-6-WT-pHLIP and the negative control [F-18]-L-K-pHLIP revealed pH dependent tumor retention. This reliable and efficient protocol promises to be useful for the F-18 labeling of large peptides such as pHLIP and will accelerate the evaluation of numerous [F-15]-pHLIP analogues as potential PET tracers.

  DOI：

  10.1021/bc3000222
• 作为产物：
  描述：

  2-溴-6-氟吡啶 、 (叔丁基二甲基)乙炔 在 copper(l) iodide 、 三乙胺 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以40%的产率得到2-((tert-butyldimethylsilyl)ethynyl)-6-fluoropyridine
  参考文献：
  名称：

  Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

  摘要：

  Solid tumors often develop an acidic microenvironment, which plays a critical role in tumor progression and is associated with increased level of invasion and metastasis. The 37 residue pH (low) insertion peptide (pHLIP) is under study as an imaging platform because of its Unique ability to insert into cell membranes at a low extracellular pH (pH(e) < 7). Labeling of peptides with [F-18] fluorine is usually performed via prosthetic groups using chemoselective coupling reactions. One of the most successful procedures involves the alkyne-azide copper(I) catalyzed cydoaddition (CuAAC). However, none of the known "click" methods have been applied to peptides as large as pHLIP. We designed a novel prosthetic group and extended the use of the CuAAC "click chemistry" for the simple and efficient F-18 labeling of large peptides. For the evaluation of this labeling approach, a D-amino acid analogue of WT-pHLIP and an L-amino acid control peptide K-pHLIP, both functionalized at the N-terminus with 6-azidohexanoic acid, were used. The novel 6-[F-18]fluoro-2-ethynylpyridine prosthetic group, was obtained via nucleophilic substitution on the corresponding bromo-precursor after 10 mm at 130 C with a radiochemical yield of 27.5 +/- 6.6% (decay corrected) with high radiochemical purity >= 98%. The subsequent Cu-I-catalyzed "click" reaction with the azido functionalized pHLIP peptides was quantitative within 5 min at 70 C in a mixture of water and ethanol using Cu acetate and sodium L-ascorbate. j D-WT-pHLIP and [F-18]-L-K-pHLIP were obtained with total radiochemical yields of 5-20% after HPLC purification. The total reaction time was 85 min including formulation. In vitro stability tests revealed high stability of the [F-18]-6-WT-pHLIP in human and mouse plasma after 120 mm, with the parent tracer remaining intact at 65% and 85%, respectively. PET imaging and biodistribution studies in LNCaP and PC -3 xenografted mice with the [F-18]-6-WT-pHLIP and the negative control [F-18]-L-K-pHLIP revealed pH dependent tumor retention. This reliable and efficient protocol promises to be useful for the F-18 labeling of large peptides such as pHLIP and will accelerate the evaluation of numerous [F-15]-pHLIP analogues as potential PET tracers.

  DOI：

  10.1021/bc3000222