3-溴-7-氯吡唑并[1,5-a]嘧啶 | 877173-84-7

• 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 - 吡唑并嘧啶类
• 中文名称: 3-溴-7-氯吡唑并[1,5-a]嘧啶
• 中文别名: 3-溴-7-氯吡唑并[1,5-A]嘧啶
• 英文名称: 3-bromo-7-chloropyrazolo[1,5-a]pyrimidine
• CAS: 877173-84-7
• 化学式: C₆H₃BrClN₃
• 分子量: 232.467
• InChiKey: LZWBPGVLNBNKSM-UHFFFAOYSA-N

物化性质

• 密度：
  2.03

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

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: 3-Bromo-7-chloropyrazolo[1,5-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: 3-Bromo-7-chloropyrazolo[1,5-a]pyrimidine
CAS number: 877173-84-7

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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.
Storage: Store in closed vessels, refrigerated.

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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: C6H3BrClN3
Molecular weight: 232.5

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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 bromide.

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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：

  3-溴-7-氯吡唑并[1,5-a]嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 ammonium hydroxide 、 potassium phosphate 、 正丁基锂 、 四丁基氟化铵 、 氨 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 水 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 15.0h， 生成 ((1R*,4S*,5R*)-3-(7-(bis(ethoxymethyl)amino)pyrazolo[1,5-a]pyrimidin-3-yl)-4,5-dihydroxycyclopent-2-en-1-yl)methyl pivalate
  参考文献：
  名称：

  基于碳环C-核苷的甲基转移酶DOT1L高选择性抑制剂的合成与分析

  摘要：

  组蛋白甲基转移酶 DOT1L 是治疗血液恶性肿瘤的一个有吸引力的治疗靶点。在这里，我们报告了基于非常规碳环 C-核苷支架的新型 DOT1L 抑制剂的设计、合成和分析。发现实验观察到的 SAR 并非微不足道，因为单个取代基的看似微小的变化导致对 DOT1L 的亲和力发生显着变化。分子模型表明，这些趋势可能与蛋白质与抑制剂相互作用后的显着构象变化有关。化合物22和 (-)- 53 ( MU1656 )，天然核苷衍生物EPZ004777的碳环 C-核苷类似物，以及临床候选物EPZ5676 (pinometostat) 在体外以及在细胞中有效且选择性地抑制 DOT1L。发现最有效的化合物MU1656比 pinometostat 本身在体内代谢更稳定且毒性显着降低。

  DOI：

  10.1021/acs.jmedchem.1c02228
• 作为产物：
  描述：

  4H-吡唑并[1,5-a]嘧啶-7-酮 在 N-溴代丁二酰亚胺(NBS) 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 3-溴-7-氯吡唑并[1,5-a]嘧啶
  参考文献：
  名称：

  Janus激酶3抑制剂的新型铰链结合母题：Tofacitinib生物等位基因的全面的结构-活性关系研究。

  摘要：

  Janus激酶（JAKs）是关键参与细胞因子信号传导的胞质酪氨酸激酶家族。JAK已被证明是治疗炎症和骨髓增生性疾病的有效靶标，两种抑制剂托法替尼和鲁索替尼最近获得了市场许可。尽管取得了成功，但JAK系列中的选择性仍然是一个主要问题。两种批准的化合物都具有共同的7 H-吡咯并[2,3- d]嘧啶铰链结合基序，关于在该杂环核心上耐受的修饰知之甚少。在当前的研究中，制备了托法替尼生物等排体库并针对JAK3进行了测试。这些化合物具有托法替尼哌啶基侧链，而铰链结合基序被模仿其药效基团的各种杂环所取代。考虑到从分子模型获得的希望，大多数化合物被证明是活性很差的。然而，发现了在这一系列新型化学型中恢复活性的策略，并推论出关键的结构-活性关系。提出的化合物可作为开发新型JAK抑制剂的起点，并可作为计算机模拟模型的有价值的训练集。

  DOI：

  10.1002/cmdc.201402252

文献信息

• Methods for inhibiting protein kinases
  申请人：Guzi J. Timothy

  公开号：US20070082900A1

  公开（公告）日：2007-04-12

  The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim kinases, and tyrosine kinase using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.

  本发明提供了使用吡唑并[1,5-a]嘧啶化合物抑制选自AKT、检查点激酶、极光激酶、Pim激酶和酪氨酸激酶的蛋白激酶的方法，以及使用这些化合物治疗、预防、抑制或改善与蛋白激酶相关的一种或多种疾病的方法。
• Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto
  申请人：Jones M. Robert

  公开号：US20060142262A1

  公开（公告）日：2006-06-29

  The present invention relates to certain fused aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些融合芳基和杂芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢性疾病及其并发症方面非常有用，如糖尿病和肥胖症。
• Pyrazolopyrimidine compounds and their use in medicine
  申请人：Parratt Martin

  公开号：US20070179161A1

  公开（公告）日：2007-08-02

  Compounds of formula (I) or salts, N-oxides, hydrates or solvates thereof are inhibitors of kinase activity, and useful for the treatment of, for example, cancer, psoriasis or restenosis: wherein ring A is an optionally substituted carbocyclic or heterocyclic radical. Alk represents an optionally substituted divalent C1-C 6 alkylene radical. n is 0 or 1. Q represents a radical of formula -(Alk 1 ) p (X) r -(Alk 2 ) s -Z wherein in any compatible combination Z is hydrogen or an optionally substituted carbocyclic or heterocyclic ring; Alk 1 and Alk 2 are optionally substituted divalent C 1 -C 6 alkylene radicals which may contain a —O—, —S— or —NR A — link, wherein R A is hydrogen or C 1 -C 6 alkyl; X represents —O—, —S—, —(C═O)—, —(C═S)—, —SO 2 —, —SO—, —C(═O)O—, —OC(═O)—, —C(═O)NR A—, —NR A C(═O)—, —C(═S)NR A , —NR A C(═S)—, —SO 2 NR A —, —NR A SO 2 —, —OC(═O)NR A—, —NR A C(═O)O—, or —NR A — wherein R A is hydrogen or C 1 -C 6 alkyl. p, r and s are independently 0 or 1. R 1 represents a radical -(Alk 3 ) a -(Y)b-(Alk 4 ) d -B wherein a, b and d are independently 0 or 1; Alk 3 and Alk 4 are optionally substituted divalent C,-C3 alkylene radicals; Y represents a monocyclic divalent carbocyclic or heterocyclic radical having from 5 to 8 ring atoms, —O—, —S—, or —NR A — wherein R A is hydrogen or C 1 -C 6 alkyl; B represents hydrogen or halo, or an optionally substituted monocyclic carbocyclic or heterocyclic ring having from 5 to 8 ring atoms, or in the case where Y is —NR A — and b is 1, then R A and the radical -(Alk 4 ) d -B taken together with the nitrogen to which they are attached may form an optionally substituted heterocyclic ring. R represents hydrogen, halo, C 1 -C 6 alkyl, C1-C 6 alkoxy, C 1 -C 6 alkylthio, phenyl, benzyl, cycloalkyl with 3 to 6 ring atoms, or a monocyclic heterocyclic group having 5 or 6 ring atoms.

  式(I)化合物或其盐、N-氧化物、水合物或溶剂合物是激酶活性的抑制剂，可用于治疗癌症、牛皮癣或再狭窄等疾病：其中环A是可选取代的碳环或杂环基。Alk表示可选取代的二价C1-C6烷基基团。n为0或1。Q表示式-(Alk1)p(X)r-(Alk2)s-Z的基团，其中Z在任何兼容的组合中为氢或可选取代的碳环或杂环环；Alk1和Alk2是可选取代的二价C1-C6烷基基团，可包含—O—、—S—或—NRA—链，其中RA为氢或C1-C6烷基；X表示—O—、—S—、—(C═O)—、—(C═S)—、—SO2—、—SO—、—C(═O)O—、—OC(═O)—、—C(═O)NRA—、—NRAC(═O)—、—C(═S)NRA、—NRAC(═S)—、—SO2NRA—、—NRASO2—、—OC(═O)NRA—、—NRAC(═O)O—或—NRA—，其中RA为氢或C1-C6烷基。p、r和s独立地为0或1。R1表示式-(Alk3)a-(Y)b-(Alk4)d-B的基团，其中a、b和d独立地为0或1；Alk3和Alk4是可选取代的二价C,-C3烷基基团；Y表示具有5至8个环原子的单环二价碳环或杂环基、—O—、—S—或—NRA—，其中RA为氢或C1-C6烷基；B表示氢或卤素，或者具有5至8个环原子的可选取代单环碳环或杂环环，或者在Y为—NRA—且b为1的情况下，RA和式-(Alk4)d-B与它们连接的氮一起可能形成可选取代的杂环环。R表示氢、卤素、C1-C6烷基、C1-C6烷氧基、C1-C6烷硫基、苯基、苄基、具有3至6个环原子的环烷基或具有5或6个环原子的单环杂环基。
• Pyrazolo [1,5-a] pyrimidine compounds and pharmaceutical compositions containing them
  申请人：Murphy Finbarr

  公开号：US20080300263A1

  公开（公告）日：2008-12-04

  The present invention relates to certain pyrazolo[1,5a]pyrimidine compounds, to processes for their preparation, compositions comprising them and methods of using them. The compounds are useful in the treatment of cancer. Novel screening methods are also provided.

  本发明涉及某些嘧唑并[1,5a]嘧啶化合物，其制备方法，包含它们的组合物和使用它们的方法。这些化合物在癌症治疗中有用。还提供了新的筛选方法。
• FUSED-ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF METABOLISM AND THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO
  申请人：Jones Robert M.

  公开号：US20100093761A1

  公开（公告）日：2010-04-15

  The present invention relates to certain fused aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些融合芳基和杂环芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢性疾病及其并发症，如糖尿病和肥胖症方面是有用的。