7-(三氟甲基)咪唑并[1,2-A]嘧啶 | 375857-66-2

• 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 - 咪唑并[1，2-a]嘧啶
• 中文名称: 7-(三氟甲基)咪唑并[1,2-A]嘧啶
• 中文别名: 7-三氟甲基咪唑并[1,2-a]嘧啶
• 英文名称: 7-(trifluoromethyl)imidazo[1,2-a]pyrimidine
• CAS: 375857-66-2
• 化学式: C₇H₄F₃N₃
• mdl: MFCD08234997
• 分子量: 187.124
• InChiKey: QBJLQUXRRGKXTD-UHFFFAOYSA-N

物化性质

• 熔点：
  163-164℃
• 密度：
  1.52

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 7-(Trifluoromethyl)imidazo[1,2-a]pyrimidine
Synonyms:

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

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Section 3. Composition/information on ingredients.
Ingredient name: 7-(Trifluoromethyl)imidazo[1,2-a]pyrimidine
CAS number: 375857-66-2

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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.
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
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C7H4F3N3
Molecular weight: 187.1

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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 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：

  7-(三氟甲基)咪唑并[1,2-A]嘧啶 在 四(三苯基膦)钯 、 溴 、 sodium acetate 、 sodium carbonate 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4,2'-difluoro-5'-(7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile
  参考文献：
  名称：

  The Expedient Synthesis of 4,2‘-Difluoro-5‘-(7-trifluoromethyl- imidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile, a GABA α2/3 Agonist

  摘要：

  An expedient regioselective synthesis of a GABA alpha 2/3 agonist 1 is described. The key step is an efficient regioselective palladium-catalyzed coupling of 7-trifluoromethylimidazo[1,2a] pyrimidine (5) to 5'-chloro-4,2'-difluorobiphenyl-2-carbonitrile ( 15). The efficiency of this step was affected by the choice of solvent, ligand, and tetrabutylammonium salt additive.

  DOI：

  10.1021/op050217j
• 作为产物：
  描述：

  2-甲基-4-(三氟甲基)嘧啶 、 2-溴-1,1-二乙氧基乙烷 在 氢溴酸 作用下， 以 乙醇 为溶剂， 反应 19.0h， 以83%的产率得到7-(三氟甲基)咪唑并[1,2-A]嘧啶
  参考文献：
  名称：

  The Expedient Synthesis of 4,2‘-Difluoro-5‘-(7-trifluoromethyl- imidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile, a GABA α2/3 Agonist

  摘要：

  An expedient regioselective synthesis of a GABA alpha 2/3 agonist 1 is described. The key step is an efficient regioselective palladium-catalyzed coupling of 7-trifluoromethylimidazo[1,2a] pyrimidine (5) to 5'-chloro-4,2'-difluorobiphenyl-2-carbonitrile ( 15). The efficiency of this step was affected by the choice of solvent, ligand, and tetrabutylammonium salt additive.

  DOI：

  10.1021/op050217j

文献信息

• [EN] PESTICIDALLY ACTIVE BI- OR TRICYCLIC HETEROCYCLES WITH SULFUR CONTAINING SUBSTITUENTS<br/>[FR] HÉTÉROCYCLES BI- OU TRICYCLIQUES À ACTION PESTICIDE AVEC SUBSTITUANTS SOUFRÉS
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2015000715A1

  公开（公告）日：2015-01-08

  Pesticidally active bi-or tricyclic heterocycles with sulphur-containing substituents, stereoisomers and tautomeric forms thereof that can be used as insecticides and can be prepared in a manner known per se.

  具有含硫取代基的杀虫活性的双环或三环杂环化合物，其立体异构体和互变异构体形式可用作杀虫剂，并可按照已知方法制备。
• Imidazo-pyrimidine derivatives as ligands for gaba receptors
  申请人：——

  公开号：US20020193385A1

  公开（公告）日：2002-12-19

  A class of 3-phenylimidazo[1,2-&agr;]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABA A receptors, in particular having good affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑[1,2-&agr;]嘧啶衍生物，苯环的间位被取代，取代基可以是直接连接或通过氧原子或-NH-键桥接的取代芳基或杂环芳基，苯环上进一步被取代为烷基，三氟甲基，烷氧基或一个或两个卤素原子，特别是氟，是GABAA受体的选择性配体，特别是对其中的&agr;2和/或&agr;3和/或&agr;5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑，惊厥和认知障碍具有益处。
• 3-Phenyl-imidazo-pyrimidine derivatives as ligands for gaba receptors
  申请人：——

  公开号：US20030176449A1

  公开（公告）日：2003-09-18

  A class of 3-phenylimidazo(1,2-&agr;) pyrimidine derivatives (of Formula I, or salt or prodrug thereof: I) wherein Y represents a chemical bond, an oxygen atom, or a —NH— linkage; Z represents an optionally substituted aryl or heteroaryl group; R 1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano trifluoromethyl, nitro, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —NR a R b , —NR a COR b , —NR a CO 2 R b , —COR a , CO 2 R a , —CONR a R b or —CR a ═NOR b ; and R a and R b independently represent hydrogen, hydrocarbon or a heterocyclic group.), substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, are selective ligands for GABA A receptors, in particular having good affinity for the a2 and/or a3 and/or a5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders. 1

  一类3-苯基咪唑并(1,2-a)嘧啶衍生物（公式I中的盐或前药：I），其中Y代表化学键，氧原子或-NH-键；Z代表可选取代的芳基或杂芳基基团；R1代表氢，碳氢化合物，杂环基团，卤素，氰基，三氟甲基，硝基，-ORa，-SRa，-SORa，-SO2Ra，-SO2NRaRb，-NRaRb，-NRaCORb，-NRaCO2Rb，-CORa，CO2Ra，-CONRaRb或-CRa═NORb；而Ra和Rb分别独立地代表氢，碳氢化合物或杂环基团，取代苯环的meta位，由氧原子或-NH-键直接连接或桥接的可选取代的芳基或杂芳基基团，是GABAA受体的选择性配体，特别是对其中的a2和/或a3和/或a5亚单位具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑，惊厥和认知障碍具有益处。
• Imidazopyridines pyrimidines and triazines for enhancing cognition as gaba-a-alphas 5 receoptor subtype ligands
  申请人：Bettati Michela

  公开号：US20060040940A1

  公开（公告）日：2006-02-23

  The present invention provides a pharmaceutical composition providing a compound of formula I or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable excipient: (I), in which: X and Y independently represent CH or N, with the proviso that if X is CH then Y is also CH; R 1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —NR a R b , —NR a COR b , —NR a CO 2 R b , —COR a , —CO 2 R a , —CONR a R b or CR a ═NOR b ; R a and R b independently represent hydrogen, hydrocarbon or a heterocyclic group; V and W are independently selected from H, halogen, C 11-6 alkyl, OH and C -1-6 alkoxy; Z represents H, halogen, CN, NO 2 , CF 3 , OCF 3 , CF 2 H, SCF 3 , R 2 , OR 3 , SR 3 , (CH 2 )pN(R 3 ) 2 , O(CH 2 )pN(R 3 ) 2 , SO 2 R 2 , SO 2 N(R 3 ) 2 , COR 4 , CO 2 R 3 , CON(R 3 ) 2 , NHCOR 4 , NR 1 (CH 2 ) n heteroaryl or O(CH 2 ) n heteroaryl the heteroaryl is optionally substituted by one, two or three groups chosen from C 1-6 alkyl, benzyl, (CH 2 )pN(R 3 ) 2 , halogen and CF 3 , R 1 is C 1-6 alkyl, where n is 1 or 2 and p is 0, 1 or 2; with the proviso that at least one of V, W and Z is other than H; R 2 represents C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or heteroaryl, any of which may bear a substituent selected from halogen, CN, NO 2 , CF 3 , OCF 3 , CF 2 H, SCF 3 , OH, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, amino, C 1-4 alkylamino, or di(C 1-4 alkyl)amino; R 3 represents H or R 2 ; or two R 3 groups bonded to the same nitrogen atom may complete a 5-7 membered nonaromatic heterocyclic ring; and R 4 represents R 3 or heteroaryl; the compounds are ligands for GABA-A receptors containing the alpha 5 subtype and thus are useful for enhancing cognition in individuals suffering from conditions such as Alzheimer's Disease.

  本发明提供了一种制药组合物，其中包含式I的化合物或其药学上可接受的盐，以及药学上可接受的载体：（I），其中：X和Y独立地表示CH或N，但如果X是CH，则Y也是CH；R1表示氢、碳氢化合物、杂环基、卤素、氰基、三氟甲基、硝基、—ORa、—SRa、—SORa、—SO2Ra、—SO2NRaRb、—NRaRb、—NRaCORb、—NRaCO2Rb、—CORa、—CO2Ra、—CONRaRb或CRa═NORb；Ra和Rb独立地表示氢、碳氢化合物或杂环基；V和W独立地选自H、卤素、C11-6烷基、OH和C-1-6烷氧基；Z表示H、卤素、CN、NO2、CF3、OCF3、CF2H、SCF3、R2、OR3、SR3、（CH2）pN（R3）2、O（CH2）pN（R3）2、SO2R2、SO2N（R3）2、COR4、CO2R3、CON（R3）2、NHCOR4、NR1（CH2）n杂环基或O（CH2）n杂环基，其中杂环基可选地被来自C1-6烷基、苯甲基、（CH2）pN（R3）2、卤素和CF3的一个、两个或三个基团取代，R1是C1-6烷基，其中n为1或2，p为0、1或2；但要求V、W和Z中至少有一个不是H；R2表示C1-6烷基、C3-6环烷基、C3-6环烷基C1-4烷基、C2-6烯基、C2-6炔基或杂环基，其中任何一种可以携带来自卤素、CN、NO2、CF3、OCF3、CF2H、SCF3、OH、C1-4烷氧基、C1-4烷氧羰基、氨基、C1-4烷基氨基或二（C1-4烷基）氨基的取代基；R3表示H或R2；或者两个结合到同一氮原子上的R3基团可以形成一个5-7成员非芳香杂环环；R4表示R3或杂环基；这些化合物是GABA-A受体的配体，包含α5亚型，因此对于患有阿尔茨海默病等疾病的个体，有助于增强认知能力。
• 3-Phenyl-imidazo-pyrimidine derivatives as ligands for GABA receptors
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06642229B2

  公开（公告）日：2003-11-04

  A class of 3-phenylimidazo(1,2-a)pyrimidine derivatives (of Formula I, or salt or prodrug thereof: I) wherein Y represents a chemical bond, an oxygen atom, or a —NH— linkage; Z represents an optionally substituted aryl or heteroaryl group; R1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano trifluoromethyl, nitro, —ORa, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NRaRb, —NRaCORb, —NRaCO2Rb, —CORa, CO2Ra, —CONRaRb or —CRa═NORb; and Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group.), substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, are selective ligands for GABAA receptors, in particular having good affinity for the a2 and/or a3 and/or a5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑并[1,2-a]嘧啶衍生物（化学式I，或其盐或前药：I），其中Y代表化学键，氧原子或—NH—连接；Z代表可选取代的芳基或杂芳基基团；R1代表氢、碳氢化合物、杂环基团、卤素、氰、三氟甲基、硝基、—ORa、—SRa、—SORa、—SO2Ra、—SO2NRaRb、—NRaRb、—NRaCORb、—NRaCO2Rb、—CORa、CO2Ra、—CONRaRb或—CRa═NORb；而Ra和Rb分别独立地代表氢、碳氢化合物或杂环基团。这些衍生物在苯环的间位上取代了可选取代的芳基或杂芳基基团，该基团直接连接或通过氧原子或—NH—连接桥接，是GABAA受体的选择性配体，特别是对a2和/或a3和/或a5亚单位具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑、惊厥和认知障碍，具有益处。