1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯 | 53554-29-3

• 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 - 有机杂环化合物 - 二嗪类
• 中文名称: 1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯
• 中文别名: 2-甲硫基-4-羟基嘧啶-5-甲酸乙酯；4-羟基-2-甲硫基嘧啶-5-甲酸乙酯；2-甲硫基-4-羟基嘧啶-5-羧酸乙酯；2-甲硫基-4-羟基-5-嘧啶甲酸乙酯；乙基-4-羟基-2-(甲硫基)嘧啶-5-羧酸乙酯；2-(甲硫基)-4-羟基嘧啶-5-甲酸乙酯；4-羟基-2-(甲硫基)嘧啶-5-羧酸乙酯
• 英文名称: ethyl 4-hydroxy-2-(methylthio)pyrimidine-5-carboxylate
• 英文别名: ethyl 2-methylsulfanyl-6-oxo-1H-pyrimidine-5-carboxylate
• CAS: 53554-29-3
• 化学式: C₈H₁₀N₂O₃S
• mdl: MFCD00023234
• 分子量: 214.245
• InChiKey: HDIWKNXVBQPJCO-UHFFFAOYSA-N

物化性质

• 熔点：
  136-144°C
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Ethyl 4-hydroxy-2-(methylsulfanyl)pyrimidine-5-carboxylate
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: Ethyl 4-hydroxy-2-(methylsulfanyl)pyrimidine-5-carboxylate
CAS number: 53554-29-3

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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.
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: C8H10N2O3S
Molecular weight: 214.2

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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

制备方法与用途

简介

1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯是一种有机中间体，可以通过将甲基硫脲硫酸盐与乙氧亚甲基丙二酸二乙酯为原料关环得到。它还是制备阿伐那非的关键中间体。

制备

将75.2g（0.4mol）甲基硫脲硫酸盐加入到质量分数为16%的NaOH溶液（250mL，1.18mol）中搅拌30分钟。然后将103.4g（0.48mol）乙氧亚甲基丙二酸二乙酯溶于160mL乙醇，并缓慢滴入反应液中。滴加完成后，在室温下继续反应10小时，直至出现大量白色固体析出。随后进行抽滤、水洗和真空干燥处理，得到白色固体（84.7g，纯度99.7%）。通过ESE-MS分析（m/z）：249[M+H]+、236.9[M+Na]+，并与文献数据比对确认为1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯。

应用

1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯可用作多种合成中间体和医药中间体，主要用于实验室研发过程及医药化工生产过程中。

反应信息

• 作为反应物：
  描述：

  1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯 在 甲醇 、 双氧水 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 、 异丙醇 、 丙酮 、 乙腈 为溶剂， 反应 29.5h， 生成 阿伐那非
  参考文献：
  名称：

  阿伐那非的制备方法

  摘要：

  本发明提供一种阿伐那非的制备方法，具体涉及药物化学技术领域，包括如下步骤：甲基硫脲硫酸和乙氧亚甲基丙二酸二乙酯作为初始原料，依次经过环合、氯化反应得到4‑氯‑2‑甲硫基嘧啶‑5‑羧酸乙酯，然后经3‑氯‑4‑甲氧基苄胺取代、水解后，与2‑氨甲基嘧啶缩合得到关键中间体4‑[(3‑氯‑甲氧基苄基)氨基]‑2‑甲硫基‑N‑(2‑嘧啶基甲基)‑5‑嘧啶甲酰胺，该中间体经氧化后与L‑脯氨醇反应生成阿伐那非。本发明具有原料易得、操作简便，反应条件温和，产品收率较高的优点。

  公开号：

  CN108707141A
• 作为产物：
  描述：

  sodium 5-(ethoxycarbonyl)-2-(methylthio)-4-oxo-4H-pyrimidin-3-ide 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 1,4-二氢-2-甲巯基-4-氧代-5-嘧啶甲酸乙酯
  参考文献：
  名称：

  [EN] DESIGN AND SYNTHESIS OF NOVEL INHIBITORS OF ISOPRENOID BIOSYNTHESIS
  [FR] CONCEPTION ET SYNTHÈSE D'INHIBITEURS INÉDITS DE LA BIOSYNTHÈSE DES ISOPRÉNOÏDES

  摘要：

  公开号：

  WO2013163159A3

文献信息

• Studies on antiallergy agents. III. Synthesis of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids and related compounds.
  作者：Kohji OZEKI、Teru ICHIKAWA、Hiroyuki TAKEHARA、Kenjiro TANIMURA、Makoto SATO、Hideya YAGINUMA

  DOI：10.1248/cpb.37.1780

  日期：——

  A series of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids with various substituents was synthesized and evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. High activity by intraperitoneal and oral administrations was observed for the 3-trifluoromethyl and 2-alkoxyanilino derivatives (64, 79, 81, 82 and 85). Structure-activity relationships are discussed.

  合成了一系列具有各种取代基的2-苯胺基-1,6-二氢-6-氧代-5-嘧啶羧酸，并在大鼠被动皮肤过敏反应试验中评估了其抗过敏活性。对于3-三氟甲基和2-烷氧基苯胺基衍生物（64、79、81、82和85），观察到腹膜内和口服给药具有高活性。讨论了构效关系。
• SULFONYL AMIDE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：Luzzio Michael Joseph

  公开号：US20090054395A1

  公开（公告）日：2009-02-26

  The present invention relates to a compound of the formula I wherein R 1 to R 6 , A, B, n and m are as defined herein. Such novel sulfonyl amide derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及一种具有以下式I的化合物 其中R 1 至R 6 ，A，B，n和m如本文所定义。这种新型磺酰胺衍生物在治疗哺乳动物（如癌症）中的异常细胞生长方面是有用的。本发明还涉及一种在治疗哺乳动物（尤其是人类）中的异常细胞生长中使用这种化合物的方法，以及含有这种化合物的药物组合物。
• Synthesis of 4-unsubstituted dihydropyrimidines. Nucleophilic substitution at position-2 of dihydropyrimidines
  作者：Hidetsura Cho、Yoshio Nishimura、Yoshizumi Yasui、Satoshi Kobayashi、Shin-ichiro Yoshida、Eunsang Kwon、Masahiko Yamaguchi

  DOI：10.1016/j.tet.2011.01.092

  日期：2011.4

  Synthesis of novel 4-unsubstituted dihydropyrimidines (DPs) was performed. Subsequently, a variety of 4-unsubstituted 1,4(3,4)-DPs with amino moieties at position-2 were obtained in excellent yields by activation of position-2 owing to regioselective alkoxycarbonylation at position-3 of the DP skeleton. 3-Oxo-2-phenyl-2,3,5,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine was obtained using phenylhydrazine

  进行了新型的4-未取代的二氢嘧啶（DPs）的合成。随后，由于在DP骨架的位置3处的区域选择性烷氧羰基化，通过位置2的活化，以优异的产率获得了在位置2具有氨基部分的各种4-未取代的1,4（3,4）-DP。使用苯肼代替胺获得3-氧代-2-苯基-2,3,5,8-四氢[1,2,4]三唑并[4,3- a ]嘧啶。根据温度和浓度，在一种衍生物的1 H NMR光谱中观察到1,4（3,4）-DP的各个互变异构体。另一方面，通过单晶X射线晶体学仅发现了固态的1，4-DP。
• Optimization of highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase
  作者：Noel A. Powell、Jennifer K. Hoffman、Fred L. Ciske、Jeffrey T. Kohrt、Sangita M. Baxi、Yun-Wen Peng、Min Zhong、Cornel Catana、Jeff Ohren、Lisa A. Perrin、Jeremy J. Edmunds

  DOI：10.1016/j.bmcl.2012.12.028

  日期：2013.2

  Optimization of the ADME properties of a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase resulted in the identification of highly selective compounds with properties suitable for use as in vitro and in vivo tools to probe the effects of Sky inhibition.

  对一系列Sky激酶的2,4-二氨基嘧啶-5-羧酰胺抑制剂的ADME性质进行优化，从而鉴定出具有适合用作体外和体内工具来探测Sky抑制作用的特性的高选择性化合物。
• Novel and orally active 5-(1,3,4-oxadiazol-2-yl)pyrimidine derivatives as selective FLT3 inhibitors
  作者：Hiroshi Ishida、Shoichi Isami、Tsutomu Matsumura、Hiroshi Umehara、Yoshinori Yamashita、Jiro Kajita、Eiichi Fuse、Hitoshi Kiyoi、Tomoki Naoe、Shiro Akinaga、Yukimasa Shiotsu、Hitoshi Arai

  DOI：10.1016/j.bmcl.2008.09.031

  日期：2008.10

  4-Oxadiazol-2-yl)pyrimidine derivative 1 was identified as a new class of FLT3 inhibitor from our compound library. With the aim of enhancement of antitumor activity of 2 prepared by minor modification of 1, structure optimization of side chains at the 2-, 4-, and 5-positions of the pyrimidine ring of 2 was performed to improve the metabolic stability. Introduction of polar substituents on the 1,3,4-oxadiazolyl

  5-（1,3,4-Oxadiazol-2-yl）嘧啶衍生物1从我们的化合物库中被鉴定为一类新的FLT3抑制剂。为了增强通过对1进行少量修饰而制备的2的抗肿瘤活性，进行了对嘧啶环2的2-，4-和5-位侧链的结构优化，以改善代谢稳定性。在1,3,4-恶二唑基上引入极性取代基有助于代谢稳定性的显着提高。结果，通过口服给药，一系列化合物在小鼠中显示出针对MOLM-13异种移植模型的增强的功效。