6-{[(1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-en-1-yl]carbonyl}-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine | 851916-38-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-{[(1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-en-1-yl]carbonyl}-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine
• 英文别名: ((1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-enyl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone；[(1S,4S)-4-(2,5-dimethylpyrrol-1-yl)-1-propan-2-ylcyclopent-2-en-1-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone
• CAS: 851916-38-6
• 化学式: C₂₄H₂₈F₃N₃O
• 分子量: 431.501
• InChiKey: BMPUZRULTXEHHF-OFNKIYASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-{[(1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-en-1-yl]carbonyl}-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine 在 盐酸羟胺 、 羟胺 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 以92%的产率得到(1S,4S)-4-isopropyl-4-{[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]carbonyl}cyclopent-2-en-1-amine
  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
• 作为产物：
  描述：

  methyl (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylate 在 甲基磺酰氯 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 7.78h， 生成 6-{[(1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-en-1-yl]carbonyl}-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine
  参考文献：
  名称：

  [EN] CYTOTOXICITY TARGETING CHIMERAS FOR C-C CHEMOKINE RECEPTOR 2-EXPRESSING CELLS
  [FR] CHIMÈRES CIBLANT LA CYTOTOXICITÉ POUR DES CELLULES EXPRIMANT LE RÉCEPTEUR 2 DE LA CHIMIOKINE C-C

  摘要：

  The present disclosure relates to heterobifunctional molecules, referred to as cytotoxicity targeting chimeras (CyTaCs) or antibody recruiting molecules (ARMs) that are able to simultaneously bind a target cell-surface protein as well as an exogenous antibody protein. The present disclosure also relates to agents capable of binding to a receptor on a surface of a pathogenic cell and inducing the depletion of the pathogenic cell in a subject for use in the treatment of cancer, inflammatory diseases, autoimmune diseases, viral infection, or bacterial infection.

  公开号：

  WO2023161874A1

文献信息

• 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。
• CCR-2 antagonist salt
  申请人：Merck & Co., Inc.

  公开号：US07473696B2

  公开（公告）日：2009-01-06

  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 are provided. The succinate salt is crystalline and has superior properties.

  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。琥珀酸盐是结晶性的，具有优异的性质。
• salt of a tetrahydropyranyl cyclopentyl tetrahydropyridopyridine derivative as CCR2-antagonist
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1682135B1

  公开（公告）日：2011-07-27