4-羟基-6-(三氟甲基)嘧啶-2-硫醇 | 368-54-7

• 物质功能分类: 化学试剂 - 有机试剂 - 硫醇盐
• 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-羟基-6-(三氟甲基)嘧啶-2-硫醇
• 中文别名: 4-羟基-6-三氟甲基嘧啶-2-硫醇
• 英文名称: 6-trifluoromethyl-2-thiouracil
• 英文别名: 2,3‐dihydro‐2‐thioxo‐6‐(trifluoromethyl)‐4(1H)‐pyrimidinone；4-Hydroxy-6-(trifluoromethyl)pyrimidine-2-thiol；2-sulfanylidene-6-(trifluoromethyl)-1H-pyrimidin-4-one
• CAS: 368-54-7
• 化学式: C₅H₃F₃N₂OS
• mdl: MFCD03425983
• 分子量: 196.153
• InChiKey: YZAOETRYQWFEOY-UHFFFAOYSA-N

物化性质

• 熔点：
  246-250 °C (lit.)
• 密度：
  1.63±0.1 g/cm3(Predicted)
• 溶解度：
  溶于甲醇
• 最大波长(λmax)：
  270nm(MeOH)(lit.)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933599090
• 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：
  存放于惰性气体中，以避免与空气接触。

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
4-Hydroxy-6-(trifluoromethyl)pyrimidine-2-thiol
Product Name:
Synonyms:

---

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

---

Section 3. Composition/information on ingredients.
4-Hydroxy-6-(trifluoromethyl)pyrimidine-2-thiol
Ingredient name:
CAS number: 368-54-7

---

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:

---

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.

---

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.

---

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.

---

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: C5H3F3N2OS
Molecular weight: 196.2

---

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, sulfur oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

4-羟基-6-(三氟甲基)嘧啶-2-硫醇是一种4-羟基取代的嘧啶类化合物。在医药和农药中间体中，嘧啶类化合物占有重要地位。

用途

作为一种嘧啶衍生物，4-羟基-6-(三氟甲基)嘧啶-2-硫醇广泛应用于制备抗癌、抗菌、抗疟疾以及治疗关节炎等药物；它还用于合成除草剂、杀虫剂和杀菌剂。例如，抗疟药乙胺嘧啶、降压药米诺地尔和抗癌药物5-氟尿嘧啶的分子结构中都含有该化合物。在农药领域，杀菌剂如乙嘧酚和甲基嘧菌胺也包含嘧啶结构。

制备

制备4-羟基-6-(三氟甲基)嘧啶-2-硫醇的过程如下：使用一个配备有机械搅拌器和回流冷凝管的250 mL三颈瓶，向其中加入27.6 g（0.15 mol）三氟乙酰乙酸乙酯、11.4 g（0.15 mol）硫脲以及100 mL DMF，并加热至120℃反应4小时。随后冷却，减压回收溶剂并析晶，过滤后用水洗涤，最终得到产物4-羟基-6-(三氟甲基)嘧啶-2-硫醇共计25.3 g（收率：86.0%）。

反应信息

• 作为反应物：
  描述：

  4-羟基-6-(三氟甲基)嘧啶-2-硫醇 在 盐酸 、 sodium hydroxide 、 五氯化磷 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 11.08h， 生成 2,4-二氯-6-三氟甲基嘧啶
  参考文献：
  名称：

  嘧啶类。6. 6-三氟甲基氯嘧啶及相关化合物

  摘要：

  对6-三氟甲基嘧啶的氯化进行了研究。在用三氯氧化磷和五氯化磷依次处理6-三氟甲基尿嘧啶（6）时，2,4-二氯-6-三氟甲基嘧啶（7）（25％）和4-氯-6-三氟甲基嘧啶-2-基二氯磷酸（ 8）（53％）获得。通过用氯化氢的三氯氧化磷溶液处理，将化合物8转化为7，产率为72％。在一锅法合成中，从6获得了7的77％。2,4,5-三氯-6-三氟甲基尿嘧啶（16）的制备类似地进行。尽管已经提出了嘧啶基二氯磷酸酯作为将嘧啶醇转化为氯嘧啶的中间体，但这些是要分离，表征并制备成环氯化嘧啶的这类化合物的第一个实例。

  DOI：

  10.1002/jhet.5570200145
• 作为产物：
  描述：

  三氟乙酰乙酸乙酯 在 sodium methylate 、 硫脲 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 4-羟基-6-(三氟甲基)嘧啶-2-硫醇
  参考文献：
  名称：

  Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as

  摘要：

  该发明涉及式(I)的嘧啶-硫代烷基和烷基醚化合物，以及式(IA)的嘧啶-硫代烷基和烷基醚化合物，即式(I)中R.sub.4选自--H或--NR.sub.15 R.sub.16组，其中R.sub.15为--H且R.sub.16为--H、C.sub.1-C.sub.6烷基、NH.sub.2或R.sub.15和R.sub.16连同--N形成1-吡咯烷基、1-吗啉基或1-哌啶基；以及R.sub.6选自--H或卤素（优选--Cl）的化合物组，总的限制条件是R.sub.4和R.sub.6不能同时为--H。式(IA)的化合物在治疗HIV阳性个体中具有抑制病毒逆转录酶的作用。

  公开号：

  US06043248A1

文献信息

• Design, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety
  作者：Liu Limin、Wang Zhengjie、Liu Xiujuan、Gao Chao、Dai Honglin、Wang Tao、Li Na、Yan Heyi、Zhang Yang、Zhang Luye、Zheng Jiaxin、Shan Lihong、Liu Hongmin、Zhang Qiurong

  DOI：10.1134/s1068162021060157

  日期：2021.11

  Abstract In order to find efficient new antitumor drugs, a series of novel pyrimidine derivatives containing urea moiety were designed and synthesized, and the antitumor activity of four human tumor cells was evaluated by MTT analysis. The results showed that most of the target compounds exhibited moderate antitumor activity. In particular, the IC50 (concentration required to achieve 50% inhibition

  摘要 为了寻找有效的新型抗肿瘤药物，设计合成了一系列含有尿素部分的新型嘧啶衍生物，并通过MTT分析评估了四种人肿瘤细胞的抗肿瘤活性。结果表明，大多数目标化合物表现出中等的抗肿瘤活性。特别地，化合物2-((4-(4-乙基苯氧基)-6-(三氟甲基)嘧啶-2-基)硫代) -N的IC 50 (实现50%抑制肿瘤细胞增殖所需的浓度)值-((4-乙基苯基)carba-moyl)乙酰胺对于 MGC-803（人胃癌细胞系）为 2.51 ± 0.17 µmol L –1，抗增殖活性明显优于阳性对照药物5-氟尿嘧啶。分子对接表明，该化合物可以与表皮生长因子受体（EGFR）的活性位点结合良好，有可能成为潜在的抗肿瘤药物。
• Synthesis of Pyrimido[2,1-b][1,3,5]Thiadiazines Containing Polyfluoroalkyl- and Amino Acid Fragments
  作者：O. G. Khudina、A. E. Ivanova、Ya. V. Burgart、V. I. Saloutin

  DOI：10.1007/s10593-014-1544-x

  日期：2014.9

  structural fragment of amino acid or its ester were synthesized by a multicomponent cyclization of 6-polyfluoroalkyl-2-thiouracils with formaldehyde and amines. The use of diamino acids allowed the preparation of bis(pyrimido-[2,1-b][1,3,5]thiadiazin-6-ones), containing an aliphatic linker with a carboxy group. Two of the synthesized compounds exhibited weak antituberculosis activity in vitro.

  通过将6-聚氟烷基-2-硫尿嘧啶与甲醛和胺类进行多组分环化反应，合成了包含氨基酸或其酯结构片段的8-多氟烷基嘧啶基[2,1-b] [1,3,5]噻二嗪-6-。 。使用二氨基酸允许制备含有具有羧基的脂族连接基的双（嘧啶-[2，1-b] [1，3，5]噻二嗪-6-酮）。两种合成的化合物在体外均显示出弱的抗结核活性。
• [EN] HETEROCYCLIC COMPOUNDS AS DELTA-5 DESATURASE INHIBITORS AND METHODS OF USE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE DELTA-5 DÉSATURASE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2021108408A1

  公开（公告）日：2021-06-03

  The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase ("D5D"). The compounds have a general Formula (I) wherein the variables of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a metabolic or cardiovascular disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

  本公开提供了用于抑制Delta-5 Desaturase ("D5D")的化合物。这些化合物具有一般的化学式（I），其中化学式（I）中的变量在此处被定义。本公开还提供了包括这些化合物的药物组合物，这些化合物的用途，以及用于治疗代谢或心血管疾病的组合物。此外，本公开提供了在合成化合物的中间体中有用的中间体。
• Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists
  作者：Yang Liu、Qing Zhang、Lin-Hai Chen、Hui Yang、Wei Lu、Xin Xie、Fa-Jun Nan

  DOI：10.1021/acsmedchemlett.6b00025

  日期：2016.6.9

  A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.

  基于高通量筛选（HTS）hit 1，设计并合成了一系列烷基嘧啶-4,6-二醇衍生物，作为新型GRP84激动剂。6-壬基吡啶-2,4-二醇被鉴定为迄今为止报道的最强效的GPR84激动剂，EC 50为0.189 nM。这些新颖的GPR84激动剂将为研究GPR84的生理功能提供有价值的工具。
• Design, synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives
  作者：Limin Liu、Zhengjie Wang、Chao Gao、Honglin Dai、Xiaojie Si、Yang Zhang、Yaqi Meng、Jiaxin Zheng、Yu Ke、Hongmin Liu、Qiurong Zhang

  DOI：10.1016/j.bmcl.2021.128268

  日期：2021.11

  novel trifluoromethyl-substituted pyrimidine derivatives were designed and synthesized, and the bioactivity against four human tumor cells (PC-3, MGC-803, MCF-7 and H1975) was evaluated by MTT assay. Compound 17v displayed potent anti-proliferative activity on H1975 (IC50 = 2.27 μΜ), which was better than the positive control 5-FU (IC50 = 9.37 μΜ). Further biological evaluation studies showed that compound

  为了寻找高效的抗肿瘤新药，设计合成了一系列新型三氟甲基取代的嘧啶衍生物，并通过MTT评估了对四种人类肿瘤细胞（PC-3、MGC-803、MCF-7和H1975）的生物活性。化验。化合物17v对H1975显示出有效的抗增殖活性（IC 50  = 2.27 μM），优于阳性对照5-FU（IC 50  = 9.37 μM）。进一步的生物学评价研究表明，化合物17v 可诱导H1975细胞凋亡，并将细胞周期阻滞在 G2/M 期。此外，化合物17v通过增加促凋亡蛋白 Bax 和 p53 的表达并下调抗凋亡蛋白 Bcl-2 诱导 H1975 细胞凋亡。此外，化合物17v能够紧密嵌入 EGFR 的活性口袋中。总之，这些结果表明化合物17v具有作为进一步研究的先导化合物的潜力。

表征谱图