methyl (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylate | 851916-45-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylate
• 英文别名: (1S,4S)-Methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-enecarboxylate；methyl (1S,4S)-4-(2,5-dimethylpyrrol-1-yl)-1-propan-2-ylcyclopent-2-ene-1-carboxylate
• CAS: 851916-45-5
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: ZOOQRHCXWMZGDG-ZBFHGGJFSA-N

物化性质

• 沸点：
  355.0±42.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylate 在 甲醇 、 sodium hydroxide 、 水 、 盐酸 作用下， 以 水 为溶剂， 反应 35.0h， 以95%的产率得到(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基-2-环戊烯羧酸
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF CCR-2 ANTAGONIST
  [FR] PROCEDE D'ELABORATION D'ANTAGONISTE VIS-A-VIS DU CCR-2

  摘要：

  本发明提供了一种高效的合成方法，用于制备((1R,3S)-3-异丙基-3- {[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种高效的合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘啶；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-{[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。该发明还在于((1R,3S)-3-异丙基-3-{[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐的优越性能。

  公开号：

  WO2005044795A1
• 作为产物：
  描述：

  2-碘代丙烷 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 7.17h， 以98%的产率得到methyl (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylate
  参考文献：
  名称：

  [EN] CCR-2 ANTAGONIST SALT
  [FR] SEL ANTAGONISTE DE CCR-2

  摘要：

  本发明提供了一种高效合成方法，用于制备((1R,3S)-3-异丙基-3-{[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种高效合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘啶；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-{[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。该发明还涉及((1R,3S)-3-异丙基-3-{[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐的优越性能。

  公开号：

  WO2005044264A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF CCR-2 ANTAGONIST<br/>[FR] PROCEDE D'ELABORATION D'ANTAGONISTE VIS-A-VIS DU CCR-2
  申请人：MERCK & CO INC

  公开号：WO2005044795A1

  公开（公告）日：2005-05-19

  The present invention provides an efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3- [3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl} cyclopentyl)[(3S,4S)-3-m ethoxytetrahydro- 2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro- 4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol- 1-yl)-1-isopropylcyclopent-2- ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1, 6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)- 4-isopropyl-4-[3-(trifluoromethyl)- 7,8-dihydro-1,6-naphthyridin-6(5H)-yl] carbonyl}cyclopent-2-e n-1-yl)- 3-methoxytetrahydro-2H- pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl- 3-[3-(trifluoromethyl)-7, 8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl} cyclopentyl)[(3S,4S)-3- methoxytetrahydro-2H-pyran-4-yl]amine.

  本发明提供了一种高效的合成方法，用于制备((1R,3S)-3-异丙基-3- [3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种高效的合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘啶；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。该发明还在于((1R,3S)-3-异丙基-3-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐的优越性能。
• Aminocyclopentyl pyridopyrazinone modulators of chemokine receptor activity
  申请人：Butora Gabor

  公开号：US20070155731A1

  公开（公告）日：2007-07-05

  Compounds of Formula I and Formula II (wherein A, E, j, k, m, n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 15 , R 16 , R 17 , R 18 , R 19 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , X, Y and Z are as defined herein) which are modulators of chemokine receptor activity and are useful in the prevention or treatment of certain inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which chemokine receptors are involved.

  化合物的化学式I和化学式II（其中A、E、j、k、m、n、R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R15、R16、R17、R18、R19、R24、R25、R26、R27、R28、R29、R30、R31、R32、R33、R34、X、Y和Z如本文所定义）是化学受体活性调节剂，可用于预防或治疗某些炎症和免疫调节性疾病，过敏性疾病，包括过敏性鼻炎、皮炎、结膜炎和哮喘，以及类风湿关节炎和动脉粥样硬化等自身免疫病理。该发明还涉及包含这些化合物的药物组合物以及在涉及化学受体的疾病的预防或治疗中使用这些化合物和组合物。
• Process for the preparation of ccr-2 antagonists
  申请人：Cai Dongwei

  公开号：US20070135475A1

  公开（公告）日：2007-06-14

  The present invention provides an efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3-[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-m ethoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro-4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)-4-isopropyl-4-[3-(tri-fluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-en-1-yl)-3-methoxytetrahydro-2H-pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl-3-1[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine.

  本发明提供了一种高效合成方法，用于制备((1R,3S)-3-异丙基-3-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种高效的合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘啶；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。本发明还在于((1R,3S)-3-异丙基-3-1[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐具有优越的性能。
• Ccr-2 antagonist salt
  申请人：Jensen Mark

  公开号：US20070135474A1

  公开（公告）日：2007-06-14

  The present invention provides an efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3-[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro-4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)-4-isopropyl-4-[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-en-1-yl)-3-methoxytetrahydro-2H-pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl-3-[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine.

  本发明提供了一种有效的合成方法，用于制备((1R,3S)-3-异丙基-3-[3-(三氟甲基)-7,8-二氢-1,6-萘咪啉-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种有效的合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘咪啉；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-[3-(三氟甲基)-7,8-二氢-1,6-萘咪啉-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。本发明还涉及((1R,3S)-3-异丙基-3-[3-(三氟甲基)-7,8-二氢-1,6-萘咪啉-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐的优越性能。
• Process for the preparation of CCR-2 antagonists
  申请人：Merck & Co., Inc.

  公开号：US07361765B2

  公开（公告）日：2008-04-22

  The present invention provides an efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3-[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-m ethoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro-4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)-4-isopropyl-4-[3-(tri-fluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-en-1-yl)-3-methoxytetrahydro-2H-pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl-3-1[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine

  本发明提供了一种有效的合成方法，用于制备((1R,3S)-3-异丙基-3-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺及其琥珀酸盐。本发明还提供了一种有效的合成方法，用于制备中间体(3R)-3-甲氧基四氢-4H-吡喃-4-酮；(1S,4S)-4-(2,5-二甲基-1H-吡咯-1-基)-1-异丙基环戊-2-烯-1-羧酸；以及3-(三氟甲基)-5,6,7,8-四氢-1,6-萘啶；以及用于制备前体(3S,4S)-N-((1S,4S)-4-异丙基-4-[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊-2-烯-1-基)-3-甲氧基四氢-2H-吡喃-4-胺。本发明还涉及((1R,3S)-3-异丙基-3-1[3-(三氟甲基)-7,8-二氢-1,6-萘啶-6(5H)-基]羰基}环戊基)[(3S,4S)-3-甲氧基四氢-2H-吡喃-4-基]胺的琥珀酸盐的优异性能。