(1R,5S)-3-propionyl-3,4,5,6-tetrahydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-8(2H)-one | 474116-07-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: (1R,5S)-3-propionyl-3,4,5,6-tetrahydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-8(2H)-one
• 英文别名: (-)-N-propionylcytisine；N-propionylcytisine；(1R,9S)-11-propanoyl-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 474116-07-9
• 化学式: C₁₄H₁₈N₂O₂
• 分子量: 246.309
• InChiKey: ONLFRWJQTUZMTI-WDEREUQCSA-N

物化性质

• 熔点：
  146-147 °C
• 沸点：
  509.8±49.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,5S)-3-propionyl-3,4,5,6-tetrahydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-8(2H)-one 在 高氯酸 作用下， 以 甲醇 为溶剂， 以75%的产率得到(1R,5S)-3-propionyl-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one perchlorate
  参考文献：
  名称：

  The amide protonation of (–)-N-benzoylcytisine in its perchlorate salts

  摘要：

  The C-13 NMR spectrum of (-)-N-benzoylcytisine perchlorate does not show a double set of signals typical of amide compounds, although this effect has been observed for the other diamine derivatives of cytisine. This observation means that in solution there must be the state of equilibrium between two forms of the cation with the protonated amide groups. DFT calculations have indeed indicated two preferred tautomeric forms with protonated oxygen atoms of amide groups. In the solid state however, according to X-ray analysis of perchlorate and perchlorate hydrate of N-benzoylcytisine the oxygen atom of the amide group in the six-membered ring A is preferred protonation site as compared with the oxygen in benzoic moiety. (-)-N-benzoylcytisine salt is the first compound from among the known derivatives of quinolizidine alkaloids that are not N-oxides, in which in solid state only the oxygen atom at cyclic amide is protonated instead of nitrogen atom or oxygen in benzoic moiety. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.saa.2014.02.192
• 作为产物：
  描述：

  丙酰氯 、 cytisine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以12.3 g的产率得到(1R,5S)-3-propionyl-3,4,5,6-tetrahydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-8(2H)-one
  参考文献：
  名称：

  Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir

  摘要：

  A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical, and chiral purities. The process was successfully demonstrated on >100 kg scale.

  DOI：

  10.1021/op500040j

文献信息

• Regio- and diastereoselective functionalization of (−)-cytisine: an unusual N–C acyl migration
  作者：Jacques Rouden、Alexis Ragot、Sonia Gouault、Dominique Cahard、Jean-Christophe Plaquevent、Marie-Claire Lasne

  DOI：10.1016/s0957-4166(02)00271-9

  日期：2002.7

  In order to test (-)-cytisine as a potential chiral inductor, N-propionyl cytisine was treated with LDA and then with benzyl bromide. Instead of the expected alpha-benzyl substituted propionamide, (-)-N-benzyl 6alpha-propionyl cytisine was formed, arising from an unusual diastereoselective nitrogen to carbon acyl migration. Using LDA in the presence of an excess of LiCl, the 6-substituted cytisine was isolated in yields of up to 79%. The efficiency of the N-C acyl transfer was shown to be dependent on the nature of the N-acyl group. Complete epimerization of the newly created stereocenter was observed under basic conditions. This methodology allows the stereoelective functionalization of the C-6 position of cytisine, an important agonist of nicotinic receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.
• The amide protonation of (–)-N-benzoylcytisine in its perchlorate salts
  作者：Anna K. Przybył、Maciej Kubicki、Marcin Hoffmann

  DOI：10.1016/j.saa.2014.02.192

  日期：2014.8

  The C-13 NMR spectrum of (-)-N-benzoylcytisine perchlorate does not show a double set of signals typical of amide compounds, although this effect has been observed for the other diamine derivatives of cytisine. This observation means that in solution there must be the state of equilibrium between two forms of the cation with the protonated amide groups. DFT calculations have indeed indicated two preferred tautomeric forms with protonated oxygen atoms of amide groups. In the solid state however, according to X-ray analysis of perchlorate and perchlorate hydrate of N-benzoylcytisine the oxygen atom of the amide group in the six-membered ring A is preferred protonation site as compared with the oxygen in benzoic moiety. (-)-N-benzoylcytisine salt is the first compound from among the known derivatives of quinolizidine alkaloids that are not N-oxides, in which in solid state only the oxygen atom at cyclic amide is protonated instead of nitrogen atom or oxygen in benzoic moiety. (C) 2014 Elsevier B.V. All rights reserved.
• Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir
  作者：Gerald J. Tanoury、Minzhang Chen、Yong Dong、Raymond Forslund、Valdas Jurkauskas、Andrew D. Jones、Daniel Belmont

  DOI：10.1021/op500040j

  日期：2014.10.17

  A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical, and chiral purities. The process was successfully demonstrated on >100 kg scale.