2-甲基氨基嘧啶-5-硼酸频那醇酯 | 904326-88-1

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸酯
• 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: 2-甲基氨基嘧啶-5-硼酸频那醇酯
• 中文别名: 2-(甲基)氨基-5-硼酸酯；2-(甲基氨基)嘧啶-5-硼酸频哪酯
• 英文名称: N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine
• CAS: 904326-88-1
• 化学式: C₁₁H₁₈BN₃O₂
• mdl: MFCD11878345
• 分子量: 235.094
• InChiKey: QDOXNCAIXITTKA-UHFFFAOYSA-N

物化性质

• 熔点：
  122-125℃
• 沸点：
  371.2±34.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.636
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
2-Methylaminopyrimidine-5-boronic acid, pinacol ester
Product Name:
Synonyms: N-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
2-Methylaminopyrimidine-5-boronic acid, pinacol ester
Ingredient name:
CAS number: 904326-88-1

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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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.

---

Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C11H18BN3O2
Molecular weight: 235.1

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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.

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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

制备方法与用途

应用中的2-(甲基)氨基-5-硼酸酯是一种有机合成中间体和医药中间体，可用于实验室研发过程和化工医药合成过程中。该化合物可通过5-溴-2-氯嘧啶作为起始物料，经过两步反应制备得到。

制备 1. 5-溴-N-甲基嘧啶-2-胺的制备

将5-溴-2-氯嘧啶（1.93 g，10 mmol）溶解在14 mL甲胺中，在130℃下微波反应40分钟。随后减压浓缩反应液，并加入20 mL水和20 mL二氯甲烷进行萃取分液。水相用二氯甲烷萃取三次（每次10 mL），合并有机相，使用饱和氯化钠溶液洗涤两次（每次10 mL），再用无水硫酸镁干燥，过滤后减压浓缩，得到粗品5-溴-N-甲基嘧啶-2-胺（1.20 g，白色固体）。此步骤未进行纯化直接进行下一步反应。质谱分析结果：[ \text{MS m/z (ESI)} = 189.9 [\text{M}+1] ]

2. 2-(甲基)氨基-5-硼酸酯的制备

将粗品5-溴-N-甲基嘧啶-2-胺（1.20 g，6.38 mmol）、双戊酰二硼（2.40 g，9.60 mmol）、[ \text{[1,1′-双(二苯基磷)二茂铁]二氯化钯} （260 mg，0.32 mmol）和醋酸钾（1.57 g，16 mmol）溶解在20 mL二氧六环中。加热至115℃搅拌反应16小时后冷却至室温。过滤后减压浓缩滤液，并通过硅胶柱色谱法以洗脱剂体系B纯化所得残余物，得到2-(甲基)氨基-5-硼酸酯（1.30 g，白色固体），产率86.6%。质谱分析结果：[ \text{MS m/z (ESI)} = 236.1 [\text{M}+1] ]

反应信息

• 作为反应物：
  描述：

  2-甲基氨基嘧啶-5-硼酸频那醇酯 、 5-[tert-butoxycarbonyl-(2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl)amino]pentanoic acid ethyl ester 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 以43%的产率得到ethyl 5-(tert-butoxycarbonyl(2-(2-(methylamino)pyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)amino)pentanoate
  参考文献：
  名称：

  TREATMENT OF CANCERS HAVING K-RAS MUTATIONS

  摘要：

  本发明提供了一种治疗与K-ras突变相关的癌症的方法，适用于需要该方法的受试者。该方法包括以下步骤：（1）识别患有与K-ras突变相关的癌症的受试者；和（2）向受试者施用（i）PI3激酶抑制剂和（ii）HDAC抑制剂，其中PI3激酶抑制剂和HDAC抑制剂以联合治疗有效的剂量进行施用。

  公开号：

  US20130102595A1
• 作为产物：
  描述：

  5-溴-2-甲基氨基嘧啶 、 联硼酸频那醇酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以100%的产率得到2-甲基氨基嘧啶-5-硼酸频那醇酯
  参考文献：
  名称：

  MORPHOLINOPURINE DERIVATIVES

  摘要：

  提供了一种新型化合物，它抑制磷脂酰肌醇3-激酶（PI3K）和/或哺乳动物雷帕霉素靶蛋白（mTOR），并表现出抗肿瘤活性。本发明提供了一种由以下式（1）表示的化合物，具有各种取代基，可抑制PI3K和/或mTOR，并表现出抗肿瘤活性： 其中R1、R2、R3、R4、Ra、Rb、Rc和X的含义与规范中定义的含义相同。

  公开号：

  US20100130492A1

文献信息

• [EN] 9H-PYRROLO-DIPYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE 9H-PYRROLO-DIPYRIDINE
  申请人：UCB BIOPHARMA SPRL

  公开号：WO2016124508A1

  公开（公告）日：2016-08-11

  The invention relates to 9H-pyrrolo-dipyridine derivatives of formula I, processes for preparing them, pharmaceutical compositions containing them and their use as radiopharmaceuticals in particular as imaging agents for the detection of Tau aggregates.

  这项发明涉及到式I的9H-吡咯-二吡啶衍生物，以及制备它们的方法、含有它们的药物组合物以及它们作为放射性药物的用途，特别是作为检测Tau聚集体的成像剂。
• MORPHOLINOPURINE DERIVATIVES
  申请人：Nakayama Kiyoshi

  公开号：US20100130492A1

  公开（公告）日：2010-05-27

  There is provided a novel compound that inhibits phosphatidylinositol 3-kinase (PI3K) and/or the mammalian target of rapamycin (mTOR) and exhibits anti-tumor activity. The present invention provides a compound represented by the following formula (1) having various substituents that inhibits PI3K and/or mTOR and exhibits anti-tumor activity: wherein R 1 , R 2 , R 3 , R 4 , R a , R b , R c , and X each have the same meaning as defined in the specification.

  提供了一种新型化合物，它抑制磷脂酰肌醇3-激酶（PI3K）和/或哺乳动物雷帕霉素靶蛋白（mTOR），并表现出抗肿瘤活性。本发明提供了一种由以下式（1）表示的化合物，具有各种取代基，可抑制PI3K和/或mTOR，并表现出抗肿瘤活性： 其中R1、R2、R3、R4、Ra、Rb、Rc和X的含义与规范中定义的含义相同。
• DNA-PK INHIBITORS
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20130281431A1

  公开（公告）日：2013-10-24

  The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及作为DNA-PK抑制剂的化合物。该发明还提供了包含所述化合物的药物可接受的组合物，以及使用所述组合物治疗各种疾病、状况或失调的方法。
• ARYL AND HETEROARYL FUSED LACTAMS
  申请人：PFIZER INC.

  公开号：US20140179667A1

  公开（公告）日：2014-06-26

  This invention relates to compounds of general formula (I) in which R 1 , R 2 , U, V, L, M, R 5 , m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

  本发明涉及具有通用公式（I）的化合物，其中R1，R2，U，V，L，M，R5，m，X，Y和Z定义如本文中所述，以及药用可接受的盐，包含此类化合物和盐的药物组合物，以及使用此类化合物、盐和组合物治疗异常细胞生长，包括癌症的方法。
• [EN] OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION<br/>[FR] INHIBITEURS OXADIAZOLE DE PRODUCTION DE LEUCOTRIÈNES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012040137A1

  公开（公告）日：2012-03-29

  The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物及其药用盐，其中R1-R5如本文所定义。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的方法以及在这些过程中有用的中间体。