(+)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate | 1893340-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate
• 英文别名: (S)-(-)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate；benzyl (3S)-3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 1893340-47-0
• 化学式: C₁₃H₁₆FNO₃
• 分子量: 253.273
• InChiKey: MDSGTKLDIYJRNX-ZDUSSCGKSA-N

物化性质

• 沸点：
  384.6±37.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 以2 g的产率得到(-)-(R)-(3-fluoropyrrolidin-3-yl)methanol
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS

  摘要：

  化合物的化学式（I）：为4-(3-氟-3-(2-(5,6,7,8-四氢-1,8-萘啶-2-基)乙基)吡咯烷-1-基)-3-(3-(2-甲氧基乙氧基)苯基)丁酸，或其盐。

  公开号：

  WO2016046225A1
• 作为产物：
  描述：

  (±)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate 在 Chiralpak AD-H 作用下， 以 乙醇 、 正庚烷 为溶剂， 生成 (+)-benzyl-3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate 、 (+)-benzyl 3-fluoro-3-(hydroxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Determination of the absolute configuration of (+)- and (−)-N-CBZ-3-fluoropyrrolidine-3-methanol using vibrational circular dichroism and confirmation of stereochemistry by conversion to (R)-tert-butyl 3-fluoro-3-(((R)-1-phenylethyl)carbamoyl)pyrrolidine-1-carboxylate

  摘要：

  Racemic N-CBZ-3-fluoropyrrolidine-3-methanol (+/-)-1 was resolved by preparative chiral HPLC. The absolute configuration of the enantiomers of 1 was identified by vibrational circular dichroism and confirmed by chemical synthesis, which involved exchanging the CBZ protecting group of (-)-1 with Boc, followed by oxidation with RuCl3, NaIO4, activation of the resulting acid with carbonyl diimidazole and reaction with (R)-alpha-methylbenzylamine to give (R)-tert-butyl 3-fiuoro-3-(((R)-1-phenylethyl)carbamoyl) pyrrolidine-l-carboxylate 7. The latter was compared with authentic (S)-tert-butyl 3-fluoro-3-(((R)-1phenylethyl)carbamoyl)pyrrolidine-l-carboxylate 6 and its diastereomer 7; the configuration of diastereomer 6 was obtained by an X-ray diffraction study. This established that the enantiomer (-)-1 had an (R)-configuration. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2016.09.008

文献信息

• [EN] NAPHTHYRIDINES AS INTEGRIN ANTAGONISTS<br/>[FR] UTILISATION DE NAPHTYRIDINES EN TANT QU'ANTAGONISTES DE L'INTÉGRINE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017162572A1

  公开（公告）日：2017-09-28

  The invention relates to compounds of Formula (I): wherein R1, R2 and R3 are as defined in the description and claims, or pharmaceutically acceptable salts thereof having ανβ6 integrin antagonist activity. The invention also relates to pharmaceutical compositions including a compound of formula (I) or a pharmaceutically acceptable salt thereof, and to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in therapy, including in the treatment of a disease or condition for which an ανβ6 integrin antagonist is indicated, and in particular the treatment of idiopathic pulmonary fibrosis.

  这项发明涉及式(I)的化合物：其中R1、R2和R3如描述和索赔中定义的，或其药学上可接受的盐，具有ανβ6整合素拮抗活性。该发明还涉及包括式(I)的化合物或其药学上可接受的盐的药物组合物，以及在治疗中使用式(I)的化合物或其药学上可接受的盐，包括治疗ανβ6整合素拮抗剂适用的疾病或症状，特别是治疗特发性肺纤维化。
• [EN] CITRATE SALT OF THE COMPOUND (S)-4-((S)-3-FLUORO-3-(2-(5,6,7,8-TETRAHYDRO-1,8-NAPHTHYDRIN-2-YL)ETHYL)PYRROLIDIN-1-YL)-3-(3-(2-METHOXYETHOXY)PHENYL) BUTANOIC ACID<br/>[FR] SEL DE CITRATE DU COMPOSÉ ACIDE (S)-4-((S)-3-FLUORO-3-(2-(5,6,7,8-TÉTRAHYDRO-1,8-NAPHTYDRIN-2-YL)ÉTHYL)PYRROLIDIN-1-YL)-3-(3-(2-MÉTHOXYÉTHOXY)PHÉNYL) BUTANOÏQUE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017158072A1

  公开（公告）日：2017-09-21

  The invention relates to a compound which is (S)-4-((S)-3-Fluoro-3-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(2-methoxyethoxy) phenyl) butanoic acid(1:1) citrate salt, pharmaceutical compositions including such compound, and to the use of such compound in therapy, including in the treatment of a disease or condition for which an αvβ6 integrin antagonist is indicated, and in particular idiopathic pulmonary fibrosis.

  这项发明涉及一种化合物，即(S)-4-((S)-3-氟-3-(2-(5,6,7,8-四氢-1,8-萘啶-2-基)乙基)吡咯烷-1-基)-3-(3-(2-甲氧基乙氧基)苯基)丁酸(1:1)柠檬酸盐，包括该化合物的药物组合物，以及该化合物在治疗中的使用，包括用于治疗αvβ6整合素拮抗剂适用的疾病或症状，特别是特发性肺纤维化。
• Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach
  作者：Rhys A Lippa、John A Murphy、Tim N Barrett

  DOI：10.3762/bjoc.16.134

  日期：——

  Integrin inhibitors based on the tripeptide sequence Arg–Gly–Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner–Wadsworth–Emmons olefination, diimide reduction, and global deprotection to synthesise cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography

  基于三肽序列Arg–Gly–Asp（RGD）的整合素抑制剂是治疗特发性肺纤维化（IPF）的潜在疗法。在本文中，我们描述了霍纳-沃兹沃思-埃蒙斯烯烃快速烯烃合成，二酰亚胺还原和整体脱保护的三步合成序列，无需色谱即可以高收率（三步获得63-83％）合成这些化合物的核。该转变的关键是对金属化步骤稳定的氨基磷酸酯保护基。
• CITRATE SALT OF THE COMPOUND (S)-4-((S)-3-FLUORO-3-(2-(5,6,7,8-TETRAHYDRO-1,8-NAPHTHYDRIN-2-YL)ETHYL)PYRROLIDIN-1-YL)-3-(3-(2-METHOXYETHOXY)PHENYL) BUTANOIC ACID
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US20200291017A1

  公开（公告）日：2020-09-17

  The invention relates to a compound which is (S)-4-((S)-3-Fluoro-3-(2-(5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(2-methoxyethoxy)phenyl) butanoic acid (1:1) citrate salt, pharmaceutical compositions including such compound, and to the use of such compound in therapy, including in the treatment of a disease or condition for which an α v J36 integrin antagonist is indicated, and in particular idiopathic pulmonary fibrosis.
• NAPHTHYRIDINES AS INTEGRIN ANTAGONISTS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US20210206758A1

  公开（公告）日：2021-07-08

  The invention relates to compounds of Formula (I): wherein R 1 , R 2 and R 3 are as defined in the description and claims, or pharmaceutically acceptable salts thereof, having α v β 6 integrin antagonist activity. The invention also relates to pharmaceutical compositions including a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and to the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, in therapy, including in the treatment of a disease or condition for which an α v β 6 integrin antagonist is indicated, in particular the treatment of idiopathic pulmonary fibrosis.