2,6-二氟吡啶-3-甲醛 | 155601-65-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2,6-二氟吡啶-3-甲醛
• 中文别名: 2,6-二氟烟醛；2,5-二氟苄醇
• 英文名称: 2,6-difluoropyridine-3-carbaldehyde
• 英文别名: 2,6-difluoronicotinaldehyde
• CAS: 155601-65-3
• 化学式: C₆H₃F₂NO
• mdl: MFCD08277633
• 分子量: 143.093
• InChiKey: ZYCCUPSLEFLBNR-UHFFFAOYSA-N

物化性质

• 熔点：
  19-20℃
• 沸点：
  64-66℃/15mm
• 密度：
  1.378

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT, KEEP COLD, STORED UNDER ARGON
• 危险品标志：
  Xi
• 海关编码：
  2933399090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 2,6-Difluoropyridine-3-carboxaldehyde
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 2,6-Difluoropyridine-3-carboxaldehyde
CAS number: 155601-65-3

---

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.
Store in closed vessels.
Storage:

---

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
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C6H3F2NO
Molecular weight: 143.1

---

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 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

应用

2,6-二氟吡啶-3-甲醛可用作医药合成中间体，可通过甲酰化制备。有文献报道其也可作为电池电解液添加剂。

制备

在氮气保护下，将2,6-二氟吡啶（4.95 g，43.0 mmol）溶解于无水THF（100 mL）中，并冷却至-78°C。然后，缓慢加入LDA（庚烷/THF/乙苯溶液，2.0 M，23.0 mL，46.0 mmol），并在该温度下搅拌30分钟。接着，滴加1-甲酰基哌啶（4.98 g，44.0 mmol），继续在-78°C下搅拌20分钟后，滴加入3N HCl水溶液（60 mL）和Et₂O（50 mL）。醚层收集后，用水洗三次（每次100 mL Et₂O萃取），合并的有机层用无水Na₂SO₄干燥。过滤去除溶剂后，通过硅胶快速色谱纯化（CH₂Cl₂/己烷，1:1 v/v），最终得到浅黄色液体状的2,6-二氟吡啶-3-甲醛（1.41 g，收率60%）。

反应信息

• 作为反应物：
  描述：

  2,6-二氟吡啶-3-甲醛 在 aluminum (III) chloride 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 48.25h， 生成 1-(2,6-difluoropyridin-3-yl)-1-(methylsulfonamido)hexan-2-yl acetate
  参考文献：
  名称：

  原子转移催化的交叉选择性氮杂频哪醇偶联

  摘要：

  已经开发了醛和亚胺的交叉选择性氮杂频哪醇偶联以提供有价值的β-氨基醇。这种策略能够在更容易还原的亚胺和其他官能团的存在下，将脂肪醛化学选择性地转化为酮基自由基。通过 AcI 进行羰基特异性活化后，光引发的 Mn 催化剂通过原子转移机制选择性地还原生成的 α-碘氧化物。随后的酮基自由基选择性地与亚胺偶联，从而阻止了通过经典还原方法进行的均二聚化。在通过原子转移催化还原酮基偶联的第一个例子中，Zn 作为末端还原剂以促进 Mn 催化剂的周转。这种新策略还可以使酮基自由基偶联到烯烃、炔烃、醛、螺旋桨和手性亚胺上。

  DOI：

  10.1021/jacs.1c00886
• 作为产物：
  描述：

  2,6-二氟-3-碘吡啶 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.25h， 生成 2,6-二氟吡啶-3-甲醛
  参考文献：
  名称：

  2,6-二氟吡啶通过有机金属中间体的结构增殖

  摘要：

  与文献声称相反，2,6-二氟吡啶-3-甲醛可以很容易地制备。通过用二异丙基氨基锂和 N,N-二甲基甲酰胺连续处理 2,6-二氟吡啶。进行了亲核试剂从醛中区域选择性置换氟。为了证明有机金属方法的多功能性，大约有两打另外的 2,6-二氟吡啶衍生物。准备好了。应用现代有机金属方法的组合，例如位点选择性氢/金属和卤素/金属置换以及去质子化触发的重卤素迁移。[在 SciFinder (R) 上]

  DOI：

  10.1002/ejoc.200300649

文献信息

• [EN] NOVEL SUBSTITUTED XANTHINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE XANTHINE SUBSTITUÉS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2019011802A1

  公开（公告）日：2019-01-17

  The present invention relates to substituted xanthine derivatives, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels.

  本发明涉及取代的黄嘌呤衍生物、含有它们的药物组合物及其在治疗中的用途，特别是在治疗与含有TRPC5的离子通道相关的病症中的用途。
• [EN] SUBSTITUTED CHROMANES AND METHOD OF USE<br/>[FR] CHROMANES SUBSTITUÉS ET MÉTHODE D'UTILISATION
  申请人：ABBVIE INC

  公开号：WO2016069757A1

  公开（公告）日：2016-05-06

  The invention provides for compounds of formula (I), wherein R1, X, Y, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, m, and R" have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjögren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

  该发明提供了一种公式（I）化合物，其中R1、X、Y、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、m和R"具有规范中定义的任何值，以及其药学上可接受的盐，这些化合物在治疗由CFTR介导和调节的疾病和症状中是有用的，包括囊性纤维化、Sjögren综合征、胰腺功能不全、慢性阻塞性肺病和慢性阻塞性气道疾病。还提供了由一个或多个公式（I）化合物组成的药物组合物。
• [EN] HETEROAROMATIC CARBOXAMIDE DERIVATIVES AS PLASMA KALLIKREIN INHIBITORS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE HÉTÉROAROMATIQUES EN TANT QU'INHIBITEURS DE LA KALLICRÉINE PLASMATIQUE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2021160718A1

  公开（公告）日：2021-08-19

  Heteroaromatic carboxamides of formula (I), wherein Y, R, and Ar are as defined in the description and the claims, and pharmaceutically acceptable salts thereof can be used in methods for the treatment of diseases which can be influenced by the inhibition of plasma kallikrein.

  式(I)中的杂环芳香族羧酰胺，其中Y、R和Ar如描述和权利要求中定义，并且其药学上可接受的盐可用于治疗受血浆激肽酶抑制影响的疾病的方法。
• [EN] HETEROCYCLIC COMPOUNDS AS HEDGEHOG SIGNALING PATHWAY INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS COMME INHIBITEURS DE LA VOIE DE SIGNALISATION HEDGEHOG
  申请人：REDX PHARMA LTD

  公开号：WO2014191737A1

  公开（公告）日：2014-12-04

  This invention relates to novel compounds of formula (I). The compounds of the invention are hedgehog pathway antagonists. Specifically, the compounds of the invention are useful as Smoothened (SMO) inhibitors. The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of the Hedgehog pathway and SMO, for example cancer.

  这项发明涉及公式（I）的新化合物。该发明的化合物是刺猬途径拮抗剂。具体来说，该发明的化合物可用作平滑蛋白（SMO）抑制剂。该发明还考虑了利用这些化合物治疗通过抑制刺猬途径和SMO可治疗的疾病，例如癌症。
• [EN] SPIRO CONDENSED BARBITURIC ACID DERIVATIVES FOR USE AS ANTIBACTERIAL<br/>[FR] DÉRIVÉS D'ACIDE BARBITURIQUE SPIRO-CONDENSÉS DESTINÉS À ÊTRE UTILISÉS COMME ANTIBACTÉRIENS
  申请人：ASTRAZENECA UK LTD

  公开号：WO2009010801A1

  公开（公告）日：2009-01-22

  In one aspect, the present invention relates to compounds of Formula (I): to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to method for their preparation.

  一方面，本发明涉及式I化合物的制备方法，以及它们的药学上可接受的盐，使用它们治疗细菌感染的方法，以及它们的制备方法。