J 104132 | 198279-45-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: J 104132
• 英文别名: (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic acid；(+)-[5S,6R,7R]-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-[3,4-methylenedioxyphenyl]cyclopenteno[1,2-b]pyridine-6-carboxylic acid；L-753037；seocalcitol；J-104132；5H-Cyclopenta(b)pyridine-6-carboxylic acid, 5-(1,3-benzodioxol-5-yl)-2-butyl-7-(2-((2S)-2-carboxypropyl)-4-methoxyphenyl)-6,7-dihydro-, (5S,6R,7R)-；(5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-2-carboxypropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid
• CAS: 198279-45-7
• 化学式: C₃₁H₃₃NO₇
• 分子量: 531.606
• InChiKey: IUHMIOAKWHUFKU-YINIXLNUSA-N

物化性质

• 沸点：
  705.9±60.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  J 104132 在 sodium hydroxide 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 16.0h， 以5.22 kg的产率得到(+)-(5S,6R,7R)-2-butyl-7-[2((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopentenol[1,2-b]pyridine-6-carboxylic acid, disodium salt
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t
• 作为产物：
  描述：

  tert-butyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate 在 chromium(VI) oxide 、 盐酸 、 高碘酸 作用下， 以 水 为溶剂， 生成 J 104132
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t

文献信息

• Asymmetric conjugate addition reaction
  申请人：Merck & Co., Inc.

  公开号：US06353110B1

  公开（公告）日：2002-03-05

  This invention relates to a key intermediate in the synthesis of an endothelin antagonist the synthesis of this key intermediate via an asymmetric conjugate addition reaction.

  这项发明涉及一种内皮素拮抗剂合成中的关键中间体，通过不对称共轭加成反应合成这种关键中间体。
• Novel use of guanylate cyclase activators for the treatment of respiratory insufficiency
  申请人：Grimminger Josef Friedrich

  公开号：US20050181066A1

  公开（公告）日：2005-08-18

  The invention relates to the novel use of guanylate cyclase activators for the treatment of partial and global respiratory failure.

  本发明涉及鸟苷酸环化酶激活剂用于治疗部分和整体呼吸衰竭的新用途。
• NOVEL USE OF GUANYLATE CYCLASE ACTIVATORS FOR THE TREATMENT OF RESPIRATORY INSUFFICIENCY
  申请人：ALTANA Pharma AG

  公开号：EP1501605A1

  公开（公告）日：2005-02-02
• [EN] NOVEL USE OF GUANYLATE CYCLASE ACTIVATORS FOR THE TREATMENT OF RESPIRATORY INSUFFICIENCY<br/>[FR] NOUVELLE UTILISATION D'ACTIVATEURS DE LA GUANYLATE CYCLASE POUR LE TRAITEMENT D'INSUFFISANCE RESPIRATOIRE
  申请人：ALTANA PHARMA AG

  公开号：WO2003090870A1

  公开（公告）日：2003-11-06

  The invention relates to the novel use of guanylate cyclase activators for the treatment of partial and global respiratory failure.
• Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist
  作者：Zhiguo J. Song、Mangzhu Zhao、Richard Desmond、Paul Devine、David M. Tschaen、Richard Tillyer、Lisa Frey、Richard Heid、Feng Xu、Bruce Foster、Jing Li、Robert Reamer、Ralph Volante、Edward J. J.Grabowski,、Ulf H. Dolling、Paul J. Reider、Shigemitsu Okada、Yoshiaki Kato、Eiichi Mano

  DOI：10.1021/jo991292t

  日期：1999.12.1

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.