2-甲硫基嘧啶-5-硼酸 | 348098-29-3

• 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 - 有机硫化合物 - 硫醚类
• 中文名称: 2-甲硫基嘧啶-5-硼酸
• 英文名称: 2-(methylthio)pyrimidine-5-boronic acid
• 英文别名: (2-methylsulfanylpyrimidin-5-yl)boronic acid
• CAS: 348098-29-3
• 化学式: C₅H₇BN₂O₂S
• mdl: MFCD07375142
• 分子量: 170.0
• InChiKey: SLNVTXVTMQIKCE-UHFFFAOYSA-N

物化性质

• 沸点：
  392.6±34.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.84
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  91.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S39
• 危险类别码：
  R37/38,R41
• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-(Methylthio)pyrimidine-5-boronic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: 2-(Methylthio)pyrimidine-5-boronic acid
CAS number: 348098-29-3

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H7BN2O2S
Molecular weight: 170.0

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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, sulfur 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

反应信息

• 作为反应物：
  描述：

  2-甲硫基嘧啶-5-硼酸 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.25h， 生成
  参考文献：
  名称：

  Development of a Series of (1-Benzyl-3-(6-methoxypyrimidin-3-yl)-5-(trifluoromethoxy)-1H-indol-2-yl)methanols as Selective Protease Activated Receptor 4 (PAR4) Antagonists with in Vivo Utility and Activity Against γ-Thrombin

  摘要：

  Here, we describe the development of a series of highly selective PAR4 antagonists with nanomolar potency and selectivity versus PAR1, derived from the indole-based 3. Of these, 9j (PAR4 IC50 = 445 nM, PAR1 response IC50 > 30 mu M) and 10h (PAR4 IC50 = 179 nM, PAR1 response IC50 > 30 mu M) maintained an overall favorable in vitro DMPK profile, encouraging rat/mouse in vivo pharmacokinetics (PK) and activity against gamma-thrombin.

  DOI：

  10.1021/acs.jmedchem.6b00928
• 作为产物：
  描述：

  5-溴-2-甲巯基嘧啶 在 正丁基锂 、 硼酸三甲酯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以64%的产率得到2-甲硫基嘧啶-5-硼酸
  参考文献：
  名称：

  Pyrimidinylmethylphenyl glucoside as novel C-aryl glucoside SGLT2 inhibitors

  摘要：

  Novel C-aryl glucoside SGLT2 inhibitors containing pyrimidine motif were designed and synthesized for biological evaluation. Among the compounds assayed, pyrimidine containing methylthio moiety 11g demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date (IC50 = 10.7 nM). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.103

文献信息

• Alkyl−(Hetero)Aryl Bond Formation via Decarboxylative Cross-Coupling: A Systematic Analysis
  作者：Frederik Sandfort、Matthew J. O'Neill、Josep Cornella、Laurin Wimmer、Phil S. Baran

  DOI：10.1002/anie.201612314

  日期：2017.3.13

  useful surrogates for alkyl halides in cross‐coupling chemistry. Such esters are easily accessible through reactions between ubiquitous carboxylic acids and coupling agents widely used in amide bond formation. This article features an amalgamation of in‐house experience bolstered by approximately 200 systematically designed experiments to accelerate the selection of ideal reaction conditions and activating

  Suzuki，Negishi和Kumada偶联是骨骼C-C键形成过程中最重要的反应。它们广泛地用于在两个芳环之间建立键，这使得化学科学的每个分支都可以使用。由于缺乏可商购的卤化物结构单元，烷基卤化物和金属化的芳基体系之间的类似结合未被广泛采用。氧化还原活性酯最近在交叉偶联化学中作为烷基卤的有用替代物出现。通过普遍存在的羧酸与广泛用于酰胺键形成的偶联剂之间的反应，可以容易地获得这类酯。
• NOVEL COMPOUNDS AS GPR119 AGONISTS
  申请人：Mankind Pharma Ltd.

  公开号：US20170291910A1

  公开（公告）日：2017-10-12

  The present invention relates to novel compounds of formula (I) as GPR119 agonist, composition compositions containing such compounds and method of preparation thereof.

  本发明涉及式(I)的新化合物作为GPR119激动剂，包含此类化合物的组合物及其制备方法。
• [EN] IMIDAZO [1, 2 - B] PYRIDAZINE DERIVATIVES AS CDPK1 INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDAZO[1,2-B]PYRIDAZINE COMME INHIBITEURS DE CDPK1
  申请人：MEDICAL RES COUNCIL TECHNOLOGY

  公开号：WO2012127212A1

  公开（公告）日：2012-09-27

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, (Formula (I)) wherein: R1 is -(CH2)nNR3R4, -OR5 or -(CH2)n-heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted by one or more R7 groups; R2 is selected from aryl, heteroaryl, fused aryl-heterocycloalkyl and fused hetero aryl-heterocycloalkyl each of which is substituted by at least one R8 group; R3 is H or alkyl; R4 is: (i) cycloalkyl optionally substituted by one or more -NR11R12 or NHCOR11 groups; or (ii) -(CH2)n-heterocycloalkyl, wherein said heterocycloalkyl is a 4, 5 or 6-membered nitrogen-containing group optionally containing one or more CO groups, wherein said heterocycloalkyl is optionally substituted by one or more one or more (CH2)nR7 groups; or (iii) alkyl substituted by one or more -NR11R12groups; or R3 and R4 are linked together with the nitrogen to which they are attached to form a 4, 5, 6 or 7-membered monocyclic heterocycloalkyl group or a bicyclic heterocyclic group, each of which optionally contains one or two further groups selected from CO, O, N and S, and which is optionally further substituted by one or more R7 groups; R5 is selected from alkyl, -(CH2)n-heteroaryl and - (CH2)n-heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl groups are each optionally substituted by one or more R7 groups; each R8 is independently selected from - NR16R17, -OR17 and -(CH2)nR17 where each R16 is H and each R17 is independently - (CHR10)n-heteroaryl, wherein said heteroaryl group is in turn optionally substituted by one or more R7 groups; each R10, R11 and R12 is independently H or alkyl; or in the case of an - NR11R12 group, R11 and R12 may be linked together with the nitrogen to which they are attached to form a 4, 5, 6 or 7-membered monocyclic or bicyclic heterocycloalkyl group optionally containing one or two further groups selected from CO, O, N and S, and which is optionally further substituted by one or more R7 groups; each m is independently an integer from 1 to 6; and each n is independently an integer from 0 to 6. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of PfCDPK1.

  该发明的第一个方面涉及式(I)的化合物，或其药学上可接受的盐或酯，其中：R1为-(CH2)nNR3R4，-OR5或-(CH2)n-杂环烷基，其中所述的杂环烷基基团可以选择性地由一个或多个R7基团取代；R2选自芳基，杂芳基，融合芳基-杂环烷基和融合杂芳基-杂环烷基，每个基团至少被一个R8基团取代；R3为H或烷基；R4为：(i) 可选择性地由一个或多个-NR11R12或NHCOR11基团取代的环烷基；或(ii) -(CH2)n-杂环烷基，其中所述的杂环烷基是一个含氮的4、5或6元环基团，可选择性地含有一个或多个CO基团，其中所述的杂环烷基可以选择性地由一个或多个(CH2)nR7基团取代；或(iii) 可选择性地由一个或多个-NR11R12基团取代的烷基；或R3和R4与它们连接到的氮原子结合在一起形成一个4、5、6或7元单环杂环烷基基团或一个双环杂环基团，每个基团可选择性地含有一个或两个进一步选择自CO、O、N和S的基团，并且可选择性地进一步由一个或多个R7基团取代；R5选自烷基，-(CH2)n-杂芳基和-(CH2)n-杂环烷基，其中所述的杂芳基和杂环烷基基团可以选择性地由一个或多个R7基团取代；每个R8独立地选自-NR16R17，-OR17和-(CH2)nR17，其中每个R16为H，每个R17独立地为-(CHR10)n-杂芳基，其中所述的杂芳基基团又可选择性地由一个或多个R7基团取代；每个R10、R11和R12独立地为H或烷基；或在-NR11R12基团的情况下，R11和R12可以与它们连接到的氮原子结合在一起形成一个4、5、6或7元单环或双环杂环烷基基团，可选择性地含有一个或两个进一步选择自CO、O、N和S的基团，并且可选择性地进一步由一个或多个R7基团取代；每个m独立地为1到6的整数；每个n独立地为0到6的整数。进一步方面涉及所述化合物在治疗各种治疗性疾病中的应用，特别是作为PfCDPK1的抑制剂。
• General Access to <i>C</i>-Centered Radicals: Combining a Bioinspired Photocatalyst with Boronic Acids in Aqueous Media
  作者：Maheshwerreddy Chilamari、Jacob R. Immel、Steven Bloom

  DOI：10.1021/acscatal.0c03422

  日期：2020.11.6

  indispensable building blocks for modern synthetic chemistry. In recent years, visible light photoredox catalysis has become a promising avenue to access C-centered radicals from a broad array of latent functional groups, including boronic acids. Herein, we present an aqueous protocol wherein water features a starring role to help transform aliphatic, aromatic, and heteroaromatic boronic acids to C-centered

  以碳为中心的自由基是现代合成化学必不可少的组成部分。近年来，可见光光氧化还原催化已成为从包括硼酸在内的广泛的潜在官能团中进入以C为中心的自由基的有前途的途径。在本文中，我们介绍了一种水性方案，其中水起着星形作用，以帮助将脂族，芳族和杂芳族硼酸转化为C具有生物启发性的黄素光催化剂的中心自由基。这些自由基通过开壳共轭物加成到不同的Michael受体上，以递送各种不同的烷基化产物，包括三种药学上相关的化合物。通过计算研究，氘标记，自由基捕获实验和光谱分析研究了反应机理。
• [EN] FUSED HETEROCYCLIC COMPOUNDS FOR USE IN THE TREATMENT OF MALARIA<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS POUR UTILISATION DANS LE TRAITEMENT DU PALUDISME
  申请人：MEDICAL RES COUNCIL TECHNOLOGY

  公开号：WO2011101640A1

  公开（公告）日：2011-08-25

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein: R1 is -NR3R4 or -OR5; R2 is selected from aryl, heteroaryl, fused aryl- heterocycloalkyl and fused heteroaryl-heterocycloalkyl each of which may be optionally substituted by one or more R8 groups; R3 is H or alkyl; R4 is: (i) cycloalkyl optionally substituted by one or more -NR11R12, -NHCO2R11, -NHCOR11 and -NHSO2R11 groups; or (ii) -(CH2)n-heterocycloalkyl, wherein said heterocycloalkyl is a 4, 5 or 6-membered nitrogen-containing group optionally containing one or more CO groups, wherein said heterocycloalkyl is optionally substituted by one or more one or more (CH2)nR7 groups; (iii) -(CH2)n-heteroaryl, wherein said heteroaryl group is optionally substituted by one or more R7 groups; or (iv) alkyl substituted by one or more -NR11R12groups; or R3 and R4 are linked together with the nitrogen to which they are attached to form a 4, 5 or 6-membered heterocycloalkyl group optionally containing one or two further groups selected from CO, O, N and S, and which is optionally further substituted by one or more R7 groups; R5 is selected from alkyl, -(CH2)n-heteroaryl and -(CH2)n-heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl groups are each optionally substituted by one or more R7 groups; each R11 and R12 is independently H or alkyl; and each n is independently an integer from O to 6; for use in treating or preventing a disorder associated with CDPK. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of PfCDPK1.

  发明的第一个方面涉及式(I)的化合物，或其药学上可接受的盐或酯，其中：R1为-NR3R4或-OR5；R2选自芳基、杂环芳基、融合芳基-杂环烷基和融合杂环芳基-杂环烷基，每种基可能被一个或多个R8基取代；R3为H或烷基；R4为：(i) 可选地被一个或多个-NR11R12、-NHCO2R11、-NHCOR11和-NHSO2R11基取代的环烷基；或(ii) -(CH2)n-杂环烷基，其中所述杂环烷基是一个含氮的4、5或6成员环基，可选地含有一个或多个CO基团，其中所述杂环烷基可被一个或多个(CH2)nR7基团取代；(iii) -(CH2)n-杂芳基，其中所述杂芳基可被一个或多个R7基团取代；或(iv) 被一个或多个-NR11R12基团取代的烷基；或R3和R4与它们连接到的氮一起形成一个含有一个或两个进一步选择自CO、O、N和S的4、5或6成员杂环烷基基团，可选地进一步被一个或多个R7基团取代；R5选自烷基、-(CH2)n-杂芳基和-(CH2)n-杂环烷基，其中所述杂芳基和杂环烷基基团可选地被一个或多个R7基团取代；每个R11和R12独立地为H或烷基；每个n独立地为0到6的整数；用于治疗或预防与CDPK相关的疾病。进一步方面涉及所述化合物在治疗各种治疗性疾病中的使用，更特别地作为PfCDPK1的抑制剂。