4,6-二氯-5-氟嘧啶 | 213265-83-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4,6-二氯-5-氟嘧啶
• 英文名称: 4,6-dichloro-5-fluoropyrimidine
• CAS: 213265-83-9
• 化学式: C₄HCl₂FN₂
• mdl: MFCD08056331
• 分子量: 166.97
• InChiKey: DGMIGAHDDPJOPN-UHFFFAOYSA-N

物化性质

• 沸点：
  50-60℃/14mm
• 密度：
  1.605±0.06 g/cm3(Predicted)
• 闪点：
  91°(196°F)
• 溶解度：
  可溶于DMSO、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险等级：
  8
• 安全说明：
  S24/25
• 海关编码：
  2933599090
• 危险品运输编号：
  UN 3265
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4,6-Dichloro-5-fluoropyrimidine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H314: Causes severe skin burns and eye damage
H318: Causes serious eye damage
H227: Combustible liquid
P210: Keep away from heat/sparks/open flames/hot surfaces. No smoking
P260: Do not breathe dust/fume/gas/mist/vapours/spray
P303+P361+P353: IF ON SKIN (or hair): Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
Store locked up
P405:

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Section 3. Composition/information on ingredients.
Ingredient name: 4,6-Dichloro-5-fluoropyrimidine
CAS number: 213265-83-9

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.

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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.
Store in closed vessels.
Storage:

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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
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C4HCl2FN2
Molecular weight: 167.0

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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
UN Number: UN3265 Class: 8 Packing group: III
Proper shipping name: CORROSIVE LIQUID, ACIDIC, ORGANIC, N.O.S. (4,6-Dichloro-5-fluoropyrimidine)

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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

制备方法与用途

用途

4,6-二氯-5-氟嘧啶化合物因其对环境污染小、价格低且稳定性好，并具有过渡金属的特性，已被广泛应用于工业化学、农业化学以及医药品化学中。它在多种氧化反应、重排反应、胺基化反应中扮演着重要角色，同时还能作为选择性氧化剂和绿色环保偶联试剂，在替代过渡金属催化反应方面也表现出色。

合成方法 步骤1

将搅拌的乙酸甲脒（1当量）溶解于乙醇（50体积），然后向其中加入含有3当量乙醇钠在乙醇（2%重量/重量）溶液的混合物。在0℃下搅拌反应混合物30分钟后，再逐滴加入氟丙二酸二乙酯（1当量）的乙醇（5vol）溶液，并继续室温下搅拌72小时。

将反应混合物冷却至0°C后，添加浓HCl（3vol），调节pH值至6。过滤所得沉淀物，用异丙醇、乙醚和己烷洗涤，得到中间体用于下一步，无需进一步纯化最终产物。

步骤2

在磷酰氯（4vol）中搅拌N,N-二甲基苯胺（1当量），然后滴加5-氟-嘧啶-4,6-二醇（1当量）。将反应混合物加热回流16小时后，冷却至室温。随后真空除去溶剂，并用冰处理所得残留物。

将残留物用乙酸乙酯（EtOAc）萃取所需中间体。有机层经MgSO4干燥、过滤和减压蒸馏去除溶剂后，得到所需的中间体用于下一步，无需进一步纯化最终产物。最终产品为4,6-二氯-5-氟嘧啶。

反应信息

• 作为反应物：
  描述：

  4,6-二氯-5-氟嘧啶 在 Ammonium hydroxide 作用下， 以 正丁醇 为溶剂， 反应 2.5h， 以57%的产率得到4-氨基-6-氯-5-氟嘧啶
  参考文献：
  名称：

  COMPOUNDS USEFUL AS RAF KINASE INHIBITORS

  摘要：

  本发明提供了作为Raf蛋白激酶抑制剂有用的化合物。本发明还提供了这些化合物的组合物，以及治疗Raf介导疾病的方法。

  公开号：

  US20090036419A1
• 作为产物：
  描述：

  4-氯-5-氟嘧啶 在 sodium ferrate(VI) 、 磷酸 、 四丁基溴化铵 、 pyridinium chlorochromate 作用下， 以 氘代二甲亚砜 、 水 为溶剂， 反应 5.5h， 以97.5%的产率得到4,6-二氯-5-氟嘧啶
  参考文献：
  名称：

  一种氟嘧菌酯中间体4,6-二氯-5-氟嘧啶的合成方法

  摘要：

  本发明公开了一种氟嘧菌酯中间体4,6‑二氯‑5‑氟嘧啶的合成方法，属于农药制药领域，其特征在于，将4‑氯‑5‑氟嘧啶和氯化试剂通过氯化反应得到4,6‑二氯‑5‑氟嘧啶，所述氯化反应过程为：1)将氯化试剂、高铁酸盐、酸和季铵盐加入到水中，在保护气下加热至110～125℃得A液，4‑氯‑5‑氟嘧啶溶于DMSO中得B液，将B液滴入A液中，控制滴加时间为40～60min，滴加结束后将体系继续升温至130～140℃，反应3～4.5h结束；2)将体系冷却后过滤除去固体，滤液用乙酸乙酯提取，提取液经洗涤、浓缩得粗品，粗品经减压蒸馏得到纯品产物氟嘧菌酯中间体。本发明副反应少，产率高，排污少，操作安全。

  公开号：

  CN108997222A

文献信息

• [EN] HETEROARYLBENZIMIDAZOLE COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROARYLBENZIMIDAZOLE
  申请人：BAYER PHARMA AG

  公开号：WO2017102091A1

  公开（公告）日：2017-06-22

  The present invention covers heteroarylbenzimidazole compounds of general formula (I) in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative and/or inflammatory disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式（I）中的杂环芳基苯并咪唑化合物，其中R1、R2、R3、R4和R5如本文所定义，制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是治疗或预防过度增殖和/或炎症性疾病的药物组合物，作为唯一活性成分或与其他活性成分组合使用。
• 作为MNK抑制剂的杂环化合物
  申请人：南京天印健华医药科技有限公司

  公开号：CN109020957B

  公开（公告）日：2023-01-13

  本发明涉及一类杂环化合物、含有其的药物组合物、以及它们的制备方法,和其作为丝裂原活化蛋白激酶相互作用激酶1和2‑MNK1/MNK2抑制剂的用途。该抑制剂为式(I)所示的杂环化合物，或其药学上可接受的盐、前药、溶剂化合物、多晶型体、异构体、稳定同位素衍生物或含有其的药物组合物。本发明涉及的化合物可用于治疗或预防由MNK介导的相关疾病，如癌症。
• [EN] PYRIMIDONE DERIVATIVES AS SELECTIVE CYTOTOXIC AGENTS AGAINST HIV INFECTED CELLS<br/>[FR] DÉRIVÉS DE PYRIMIDONE EN TANT QU'AGENTS CYTOTOXIQUES SÉLECTIFS CONTRE DES CELLULES INFECTÉES PAR LE VIH
  申请人：MERCK SHARP & DOHME

  公开号：WO2020131597A1

  公开（公告）日：2020-06-25

  The present disclosure is directed to pyrimidone derivatives of Formula I and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV nave cells, and for the treatment or prophylaxis of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).

  本公开涉及式I的嘧啶酮衍生物及其用于选择性杀灭HIV感染的GAG-POL表达细胞而不对HIV天然细胞产生细胞毒性，并用于治疗或预防HIV感染，或用于治疗、预防或延缓艾滋病或艾滋病相关综合症（ARC）的发病或进展。
• [EN] PRMT5 INHIBITORS<br/>[FR] INHIBITEURS DE PRMT5
  申请人：LUPIN LTD

  公开号：WO2020250123A1

  公开（公告）日：2020-12-17

  The invention relates to substituted nucleoside analogues of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions for treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme. The invention also relates to methods of treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme.

  该发明涉及公式（I）的替代核苷类似物，其药用盐以及用于治疗与PRMT5酶过度表达相关的疾病、紊乱或状况的药物组合物。该发明还涉及治疗与PRMT5酶过度表达相关的疾病、紊乱或状况的方法。
• [EN] AZABENZOTHIAZOLE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS D'AZABENZOTHIAZOLE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012035039A1

  公开（公告）日：2012-03-22

  Provided are compounds of Formula I, stereoisomers, tautomers, solvates, prodrugs and pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, and methods of 5 manufacturing a compound of Formula I.

  提供的是公式I的化合物，立体异构体，互变异构体，溶剂合物，前药和其药学上可接受的盐，其中A、X、R1、R2、R4和R5在此处被定义，包括公式I的化合物和药学上可接受的载体、辅料或载体的药物组合物，使用该化合物或组合物进行治疗的方法，以及制造公式I的化合物的方法。