exo-2-(2'-fluoro-5'-pyridyl)-7-azabicyclo<2.2.1>heptane | 163517-84-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 地棘蛙素类似物
• 英文名称: exo-2-(2'-fluoro-5'-pyridyl)-7-azabicyclo<2.2.1>heptane
• 英文别名: 2-exo-(2'-fluoro-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane；exo-2-(2'-fluoro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane；fluoro-norchloro-epibatidine；norchlorofluoroepibatidine；2-(2-Fluoro-5-pyridyl)-7-azabicyclo(2.2.1)heptane, exo-(+/-)-；(1R,2R,4S)-2-(6-fluoropyridin-3-yl)-7-azabicyclo[2.2.1]heptane
• CAS: 163517-84-8
• 化学式: C₁₁H₁₃FN₂
• 分子量: 192.236
• InChiKey: DCJIJGZSYBOUGL-IVZWLZJFSA-N

物化性质

• 沸点：
  311.7±32.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  exo-2-(2'-fluoro-5'-pyridyl)-7-azabicyclo<2.2.1>heptane 、 三氟甲烷磺酸甲酯 以 二氯甲烷 为溶剂， 以22%的产率得到(1R,2R,4S)-2-(6-Fluoro-pyridin-3-yl)-7-methyl-7-aza-bicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Evaluation of N-[¹¹C]Methylated Analogues of Epibatidine as Tracers for Positron Emission Tomographic Studies of Nicotinic Acetylcholine Receptors

  摘要：

  Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They were (+)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7- azabicyclo[2.2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl analogues 1, 2, 3, and 4 inhibited the in vitro binding of [H-3]epibatidine to nAChRs to a similar degree, with affinities in the 27-50 pM range. The binding affinity of N-ethylepibatidine (2b), however, was substantially lower. The N-[C-11]methyl derivatives of 1, 2, and 3 were synthesized from high-specific radioactivity [C-11]methyl iodide using a high-temperature/high-pressure technique. The corresponding radiolabeled compounds [C-11]1a, [C-11]2a, and [C-11]3a were administrated to mice intravenously. The pattern of regional distribution of the three tracers in the mouse brain following intravenous administration matched those of [H-3]epibatidine, [H-3]norchloroepibatidine, and (+/-)-exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([F-18]FPH), which are highly specific nAChR probes. The initial brain uptake of the C-11 analogues and the acute toxicity of the corresponding authentic nonlabeled compounds appeared to be related to their lipophilicity.

  DOI：

  10.1021/jm980233p
• 作为产物：
  描述：

  2-溴-5-碘吡啶 在 potassium fluoride 、 四(三苯基膦)钯 、 甲酸 、 piperadine 、 氢溴酸 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 exo-2-(2'-fluoro-5'-pyridyl)-7-azabicyclo<2.2.1>heptane
  参考文献：
  名称：

  Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: (+/−)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane

  摘要：

  The radiochemical synthesis of (+/-)-exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1] heptane ([F-18]1) was accomplished by Kryptofix(R) 222 assisted nucleophilic no-carrier-added [F-18]fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-azabicyclo[2.2.1] heptane (3a). The average radiochemical yield of the final product was 10% and the average specific activity was greater than >2000 mCi/mu mol, calculated at end-of-synthesis. The stable fluorine ligand ([F-19]1) was prepared by Kryptofix(R) 222 assisted nucleophilic fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-methoxycarbonyl-7-azabicyclo [2.2.1]heptane (3b) followed by acid deprotection.

  DOI：

  10.1002/(sici)1099-1344(199604)38:4<355::aid-jlcr842>3.0.co;2-3

文献信息

• Synthesis of a fluorine-18 labeled derivative of epibatidine for in vivo nicotinic acetylcholine receptor PET imaging
  作者：Lilian Dolci、Frédéric Dolle、Héric Valette、Françoise Vaufrey、Chantal Fuseau、Michel Bottlaender、Christian Crouzel

  DOI：10.1016/s0968-0896(98)00261-2

  日期：1999.3

  (exo-2-(2'-chloro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a natural compound isolated from the skin of the Ecuadorian poison frog Epipedobates tricolor, is the most potent nicotinic acetylcholine receptor (nAChR) agonist reported to date. In order to visualize and quantify in vivo these receptors in human brain using Positron Emission Tomography (PET), [18F]norchlorofluoroepibatidine (exo-2-(2'-[18F]

  Epibatidine（exo-2-（2'-chloro-5'-吡啶基）-7-azabicyclo [2.2.1]庚烷）是从厄瓜多尔毒蛙Epipedobates的皮肤中分离出来的天然化合物，是最有效的烟碱乙酰胆碱迄今为止报道的受体（nAChR）激动剂。为了可视化和定量体内使用正电子发射断层扫描（PET），[18F] norchlorofluoroepibatidine（exo-2-（2'-[18F] fluoro-5'-吡啶基）-7-azabicyclo [2.2设计了.1]庚烷），一种氟-18（t（1/2）：110分钟）放射性标记的依巴替丁衍生物。相应的2'-溴-，2'-碘和2'-硝基exo-2-（5'-吡啶基）-7-氮杂双环[2.2.1]庚烷类似物作为标记前体，以及正氯氟哌啶该化合物已通过还原，立体选择性，N-Boc保护的金刚降冰片与相应的氯吡啶之间的钯催化的Heck型偶联。[18F]
• Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 2-<i>exo</i>-2-(2‘-Substituted 5‘-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine Analogues
  作者：F. Ivy Carroll、Feng Liang、Hernán A. Navarro、Lawrence E. Brieaddy、Philip Abraham、M. I. Damaj、Billy R. Martin

  DOI：10.1021/jm0100178

  日期：2001.6.1

  A convenient, high-yield synthesis of 7-tert-butoxycarbonyl-7-azabicyclo[2.2.1]hept-2-ene (5), which involved the addition of tributyltin hydride to 7-tert-butoxycarbonyl-2-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-ene (4) followed by elimination of the tributyltin and p-tolylsulfonyl groups using tetrabutylammonium fluoride was developed. The addition of 2-amino-5-iodopyridine to 5 under reductive

  一种方便，高产的7-叔丁氧基羰基-7-氮杂双环[2.2.1]庚-2-烯（5）的合成方法，该方法涉及将氢化三丁基锡加到7-叔丁氧基羰基-2-对甲苯磺酰基中开发了-7-氮杂双环[2.2.1]庚-2-烯（4），然后用氟化四丁基铵消除三丁基锡和对甲苯磺酰基。在还原性Heck条件下将2-氨基-5-碘吡啶加入到5中，得到7-叔丁氧基羰基-2-exo-（2'-氨基-5'-吡啶基）-7-氮杂双环[2.2.1]庚烷（6 ）。化合物6是用于制备Epibatidine类似物的关键中间体，其中吡啶环上的2'-氯基被氟（1b），溴（1c），碘（1d），羟基（1e），氨基（1f）取代，二甲氨基（1g），三氟甲磺酸盐（1h）和氢（1i）基团。（+）-和（-）-表哌丁啶以及化合物1b-d和1i在由[（3）H]表哌丁啶标记的alpha（4）beta（2）nAChR受体上都具有相似的结合亲和力。化合物1f具有与尼古丁相似的亲
• Synthesis and Nicotinic Acetylcholine Receptor Binding Properties of <i>exo</i>-2-(2‘-Fluoro-5‘-pyridinyl)-7-azabicyclo- [2.2.1]heptane:  A New Positron Emission Tomography Ligand for Nicotinic Receptors
  作者：Feng Liang、Hernán A. Navarro、Philip Abraham、Pravin Kotian、Yu-Shin Ding、Joanna Fowler、Nora Volkow、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm970187d

  日期：1997.7.1
• Dolci; Dolle; Valette, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S502-S503
  作者：Dolci、Dolle、Valette、Vaufrey、Bottlaender、Crouzel

  DOI：——

  日期：——
• Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: (+/−)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane
  作者：Andrew Horti、Hayden T. Ravert、Edythe D. London、Robert F. Dannals

  DOI：10.1002/(sici)1099-1344(199604)38:4<355::aid-jlcr842>3.0.co;2-3

  日期：1996.4

  The radiochemical synthesis of (+/-)-exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1] heptane ([F-18]1) was accomplished by Kryptofix(R) 222 assisted nucleophilic no-carrier-added [F-18]fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-azabicyclo[2.2.1] heptane (3a). The average radiochemical yield of the final product was 10% and the average specific activity was greater than >2000 mCi/mu mol, calculated at end-of-synthesis. The stable fluorine ligand ([F-19]1) was prepared by Kryptofix(R) 222 assisted nucleophilic fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-methoxycarbonyl-7-azabicyclo [2.2.1]heptane (3b) followed by acid deprotection.