4,4-二氟哌啶盐酸盐 | 144230-52-4

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4,4-二氟哌啶盐酸盐
• 中文别名: 4,4-二氟哌啶(盐酸盐)
• 英文名称: 4,4-difluoropiperidine hydrochloride
• 英文别名: 4,4-difluoropiperidin-1-ium chloride；4,4-difluoropiperidine hydrogen chloride；4,4-difluoropiperdine hydrochloride；4,4-difluoropiperidine hydrochloride salt；4,4-difluoropiperidine monohydrochloride；4,4-difluoropiperidine HCl salt；4,4-Difluoropiperidine;hydron;chloride；4,4-difluoropiperidine;hydron;chloride
• CAS: 144230-52-4
• 化学式: C₅H₉F₂N*ClH
• mdl: MFCD03095381
• 分子量: 157.591
• InChiKey: OABUKBBBSMNNPM-UHFFFAOYSA-N

物化性质

• 熔点：
  173-177 °C
• 稳定性/保质期：
  避氧化物

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36
• WGK Germany：
  3
• 海关编码：
  2933399090
• 危险品运输编号：
  NONH for all modes of transport
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H319
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 4,4-Difluoropiperidine, HCl
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H319: Causes serious eye irritation
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

---

Section 3. Composition/information on ingredients.
Ingredient name: 4,4-Difluoropiperidine, HCl
CAS number: 144230-52-4

---

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.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
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.

---

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.

---

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.

---

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.

---

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.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H10ClF2N
Molecular weight: 157.6

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

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

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

4,4-二氟哌啶盐酸盐是哌啶类衍生物，在医药中间体领域需求量很大。它也是新型组胺-3受体拮抗剂的重要组成部分。

制备方法

在50升干燥的四口瓶中一次性加入20公斤二氯甲烷，然后一次性加入2公斤A1（此时内温为25℃），加料过程中的温度保持不变。之后将反应体系降温至15-20℃，并置换为空气。采用滴加方式，逐步加入2.2公斤三氟硫基吗啉（滴加时间240分钟）。在加料过程中会放热和放气，但过程较为平稳。保持内温低于30℃，在25-30℃下搅拌10小时。搅拌过程相对容易。通过TLC监测反应进度（PE: EA= 3:1），使用茚三酮作为显色剂，显示原料已完全反应，并生成新的产物点。经GC检测，产品含量为95%，消除产物含量为2%。

反应信息

• 作为反应物：
  描述：

  4,4-二氟哌啶盐酸盐 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 17.0h， 生成 5-(3-{[2-(difluoromethoxy)phenyl]methyl}-2-methylimidazo[1,2-a]pyrazin-6-yl)-2-(4,4-difluoropiperidin-1-yl)pyrimidine
  参考文献：
  名称：

  [EN] IMIDAZOPYRAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
  [FR] DÉRIVÉS D'IMIDAZOPYRAZINE EN TANT QUE MODULATEURS DE L'ACTIVITÉ TNF

  摘要：

  一系列咪唑并[1,2-α]吡嗪衍生物，作为强效的人类TNFα活性调节剂，因此在治疗和/或预防各种人类疾病方面具有益处，包括自身免疫和炎症性疾病；神经和神经退行性疾病；疼痛和伤害感知性疾病；心血管疾病；代谢性疾病；眼部疾病；以及肿瘤性疾病。

  公开号：

  WO2014009296A1
• 作为产物：
  描述：

  4,4-二氟哌啶-1-甲酸叔丁酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.2h， 生成 4,4-二氟哌啶盐酸盐
  参考文献：
  名称：

  [EN] NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS D'AMIDE SUBSTITUÉS BÉTULINIQUES UTILISÉS COMME INHIBITEURS DU VIH

  摘要：

  本发明涉及新的取代苦杏仁酸酰胺化合物的化学式(I)；以及其药用盐，其中R1、R2、R3、R4、R5、R6、R7、R8、X、Y、Z1、Z2、Z3和在此定义的化学式(II)。该发明涉及新的取代苦杏仁酸酰胺衍生物、相关化合物和药物组合物，用于治疗病毒性疾病，特别是HIV介导的疾病。

  公开号：

  WO2017017630A1
• 作为试剂：
  描述：

  (3S)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester 在 4,4-二氟哌啶盐酸盐 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 以86%的产率得到(S)-3-fluoropyrrolidine hydrochloride
  参考文献：
  名称：

  PYRAZOLE DERIVATIVES

  摘要：

  由式(I)表示的化合物： （其中Ar1代表可能具有1到3个取代基的苯基，或者是非取代的5-或6-成员芳香杂环基团；Ar2代表（i）非取代的苯基团，（ii）已被1到3个来自羰胺基、氨基、羟基、低烷氧基和卤原子的群或原子取代的较低烷基基团取代的苯基团，或者（iii）已被1到3个来自低烷基基团、低炔基基团、低烷酰基团、羰胺基、氰基、氨基、羟基、低烷氧基和卤原子的群或原子取代的5-或6-成员含氮芳香杂环基团；X代表由式(II)表示的基团： （其中环结构表示可能具有除了式(II)中显示的氮原子之外，从氮、氧和硫中选择的一个杂原子的4-到7-成员杂环基团，并且可能被1到4个来自低烷基基团、羰胺基、氨基、羟基、低烷氧基、氧基、低烷酰基团、低烷基磺酰基团和卤原子的群或原子取代）），其盐，该化合物或其盐的溶剂化合物，以及药物。

  公开号：

  EP1762568A1

文献信息

• [EN] 2-QUINOLONE DERIVED INHIBITORS OF BCL6<br/>[FR] INHIBITEURS DE BCL6 DÉRIVÉS DE 2-QUINOLONE
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2018215798A1

  公开（公告）日：2018-11-29

  The present invention relates to compounds of formula I that function as inhibitors of BCL6(B- cell lymphoma 6) activity: Formula I wherein X1, X2, X3, R1, R2, R3, R4 and R5 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer,as well as other diseases or conditions in which BCL6 activity is implicated.

  本发明涉及作为BCL6（B细胞淋巴瘤6）活性抑制剂的I式化合物：式中X1、X2、X3、R1、R2、R3、R4和R5分别如本文所定义。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增生性疾病（如癌症）以及其他BCL6活性所涉及的疾病或病况中的用途。
• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉASES À CYSTÉINE DE TYPE CATHEPSINES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015054038A1

  公开（公告）日：2015-04-16

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类新型化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• [EN] PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS<br/>[FR] PYRROLOTRIAZINES EN TANT QU'INHIBITEURS D'ALK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2010071885A1

  公开（公告）日：2010-06-24

  The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了一种式（I）的化合物或其盐形式，其中Q1、Q2、Q3和Q4如本文所定义。式（I）的化合物具有ALK和/或JAK2抑制活性，并可用于治疗增殖性疾病。
• N-ARYLAMIDINE-SUBSTITUTED TRIFLUOROETHYL SULFIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
  申请人：BAYER CROPSCIENCE AG

  公开号：US20140315898A1

  公开（公告）日：2014-10-23

  The present invention relates to novel N-arylamide-substituted trifluoroethyl sulfide derivatives of the formula (I) in which X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , n have the meanings given in the description—to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation

  本发明涉及公式（I）中的新型N-芳酰胺取代三氟乙基硫醚衍生物，其中X1、X2、X3、X4、R1、R2、R3、n的含义如描述所示—它们作为杀螨剂和杀虫剂用于控制动物害虫，并涉及其制备的过程和中间体。
• [EN] FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1<br/>[FR] DÉRIVÉS DE 1,4-DIHYDRODIOXINE FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE FACTEUR DE TRANSCRIPTION 1 DU CHOC THERMIQUE
  申请人：CANCER REC TECH LTD

  公开号：WO2015049535A1

  公开（公告）日：2015-04-09

  The present invention relates to compounds of formula I wherein A1, A2 R4 and Q are as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中A1、A2、R4和Q如本文所定义。本发明的化合物是热休克因子1（HSF1）的抑制剂。具体来说，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。