4,4-二氟-L-脯氨酰胺 盐酸盐 | 426844-51-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4,4-二氟-L-脯氨酰胺 盐酸盐
• 中文别名: 4,4-二氟-L-脯氨酰胺盐酸盐
• 英文名称: (S)-4,4-difluoropyrrolidine-2-carboxamide hydrochloride
• 英文别名: 4,4-difluoro-L-prolinamide hydrochloride；(2S)-4,4-difluoropyrrolidine-2-carboxamide;hydrochloride
• CAS: 426844-51-1
• 化学式: C₅H₈F₂N₂O*ClH
• 分子量: 186.589
• InChiKey: RRQDQYAEZGKHOB-DFWYDOINSA-N

物化性质

• 熔点：
  222°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 稳定性/保质期：
  避氧化物

计算性质

• 辛醇/水分配系数(LogP)：
  -0.11
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  55.1
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  请将药品存放在密闭、阴凉、干燥的地方。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4,4-Difluoro-l-prolinamide, HCl
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: 4,4-Difluoro-l-prolinamide, HCl
CAS number: 426844-51-1

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Storage: Store in closed vessels.

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H8F2N2O.ClH
Molecular weight: 186.6

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride, hydrogen fluoride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4,4-二氟-L-脯氨酰胺 盐酸盐 在 咪唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氯氧磷 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.17h， 生成 trans-tert-butyl (3S,5S)-3-(2-(tert-butoxy)-2-oxoethyl)-5-((S)-2-cyano-4,4-difluoropyrrolidine-1-carbonyl)-2-oxopyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] FIBROBLAST ACTIVATION PROTEIN (FAP)-TARGETED IMAGING AND THERAPY OF CANCERS AND OTHER FIBROTIC AND INFLAMMATORY DISEASES
  [FR] IMAGERIE CIBLÉE DE PROTÉINE D'ACTIVATION DES FIBROBLASTES (FAP) ET THÉRAPIE DE CANCERS ET D'AUTRES MALADIES FIBROTIQUES ET INFLAMMATOIRES

  摘要：

  纤维母细胞活化蛋白（FAP）靶向化合物（例如，共轭物）；一种用于影像癌症或纤维化的方法；以及治疗炎症性疾病/紊乱和癌症的方法。

  公开号：

  WO2021055641A1
• 作为产物：
  描述：

  N-Boc-4,4-二氟-L-脯氨酸 在 盐酸 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 4,4-二氟-L-脯氨酰胺 盐酸盐
  参考文献：
  名称：

  有效的3-或4-取代的-2-氰基吡咯烷二肽基肽酶IV抑制剂的合成及其构效关系。

  摘要：

  作为用于治疗2型糖尿病的潜在药物，二肽基肽酶IV（DPP-IV）抑制剂引起了人们的注意，因为它们可防止胰高血糖素样肽1（GLP-1）降解并延长其作用时间。一系列的2-氰基吡咯烷是最有效的DPP-IV抑制剂。我们将注意力集中在2-氰基吡咯烷的3-或4-位的取代上，并合成和评估了各种衍生物。在它们之中，发现4-氟衍生物与4-未取代的衍生物相比，口服给予大鼠后显示出更好的DPP-IV抑制活性和更高的血浆药物浓度。我们在这里报告上述衍生物的合成和生物学数据。

  DOI：

  10.1016/j.bmc.2004.09.010

文献信息

• [EN] 2-CYANOPYRROLIDINE DERIVATIVES AND THEIR USE AS DPP-IV INHIBITORS<br/>[FR] DERIVES 2-CYANOPYRROLIDINE ET LEUR UTILISATION COMME INHIBITEURS DE LA DPP-IV
  申请人：FUJISAWA PHARMACEUTICAL CO

  公开号：WO2004099185A1

  公开（公告）日：2004-11-18

  A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X is CFH, or CF?2#191, R1 is the moiety represented by the formula: [wherein R2 is (lower)alkyl, R3 is phenyl-(lower)alkyl, and the like.], and the like.] Compounds of formula (I) inhibit DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.

  化合物的结构式（I）或其药学上可接受的盐：[其中X为CFH，或CF?2＃191，R1为由以下结构式表示的基团：[其中R2为（较低）烷基，R3为苯基-（较低）烷基等。]，等等。] 公式（I）的化合物抑制DPP-IV活性。因此，它们在治疗由DPP-IV介导的疾病，如NIDDM中是有用的。
• [EN] NOVEL FAP INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE FAP
  申请人：UNIV ANTWERPEN

  公开号：WO2013107820A1

  公开（公告）日：2013-07-25

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及对FAP（成纤维细胞活化蛋白）具有高选择性和特异性的新型抑制剂。所述抑制剂可用作人类和/或兽药，特别是用于治疗和/或预防FAP相关疾病，如但不限于增殖性疾病。
• A modular CuI-L-proline catalyzed one-pot route for the rapid access of constrained and privileged hetero-atom-linked medium-sized ring systems
  作者：Vunnam Srinivasulu、Kim D. Janda、Imad A. Abu-Yousef、Matthew John O'Connor、Taleb H. Al-Tel

  DOI：10.1016/j.tet.2017.02.061

  日期：2017.4

  4]diazepin, benzo[e]pyrrolo[1,2-a][1,4]diazocin, benzo[e]pyrido[1,2-a][1,4]diazocinones, dibenzo[b,f][1,5]diazoninones, dihydrodibenzo[b,e][1,4]thiazepine, dibenzo[b,e][1,4]thiazocine and benzo[6,7][1,4]diazepino[1,2-a]indole. Moreover, the synthetic procedures described herein, allows rapid entries to synthetically challenging medium-sized heterocyclic systems with good overall yields.

  开发了一种有效的CuI-L-脯氨酸催化的一锅合成方法，以生成一系列骨架多样的杂环系统，大小范围为6至9。该设计策略的显着特征是其使用S N 2反应的模块化合成效用。随后是微波辅助的CuI-L-脯氨酸杂芳基化反应，该化合物已获得一系列杂环骨架的访问权，其中包括：苯并[e]吡咯并[1,2-a] [1,4]二氮杂，苯并[e]吡咯并[1,2-a] [1,4]二唑啉，苯并[e]吡啶基[1,2-a] [1,4]重氮酮，二苯并[b，f] [1,5]重氮酮，二氢二苯并[b， e] [1,4] thiazepine，二苯并[b，e] [1,4]噻唑嗪和苯并[6,7] [1,4]二氮杂p [1,2- a]吲哚。此外，本文所述的合成方法允许以良好的总收率快速进入具有合成挑战性的中型杂环系统。
• NOVEL FAP INHIBITORS
  申请人：UNIVERSITEIT ANTWERPEN

  公开号：US20140357650A1

  公开（公告）日：2014-12-04

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及具有高选择性和特异性的新型抑制剂，用于FAP（成纤维细胞激活蛋白）。所述抑制剂可用作人类和/或兽医药物，特别用于治疗和/或预防与FAP相关的疾病，如但不限于增殖性疾病。
• [EN] DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS<br/>[FR] COMPOSÉS DIHYDROPYRIMIDINE ET LEUR APPLICATION DANS DES PRODUITS PHARMACEUTIQUES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2015074546A1

  公开（公告）日：2015-05-28

  Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.

  本文提供了二氢嘧啶化合物及其药物应用，特别用于治疗和预防HBV疾病。具体来说，本文提供了具有化学式（I）或（Ia）的化合物，或其对映体、二对映异构体、互变异构体、水合物、溶剂合物或其药学上可接受的盐，其中化学式的变量如规范中所定义。本文还提供了利用具有化学式（I）或（Ia）的化合物，或其对映体、二对映异构体、互变异构体、水合物、溶剂合物或其药学上可接受的盐来治疗和预防HBV疾病。