2-氨基-4-氯吡咯并[2,3-d]嘧啶 | 84955-31-7

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 2-氨基-4-氯吡咯并[2,3-d]嘧啶
• 中文别名: 2-氨基-4-氯吡咯并嘧啶；2-氨基-4-氯吡咯并[2,3-D]嘧啶；6-氯-7-脱氮鸟嘌呤
• 英文名称: 4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine
• 英文别名: 2-amino-4-chloro-7H-pyrrolo[2,3-d ]pyrimidine；2-amino-4-chloropyrrolo[2,3-d]pyrimidine；2-amino-6-chloro-7-deazapurine；6-chloro-7-deazaguanine；2-amino-4-chloro-1H-pyrrolo[2,3-d]pyrimidine；4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine
• CAS: 84955-31-7
• 化学式: C₆H₅ClN₄
• mdl: MFCD07369229
• 分子量: 168.585
• InChiKey: VIVLSUIQHWGALQ-UHFFFAOYSA-N

物化性质

• 熔点：
  215-217°C
• 沸点：
  346.6±52.0 °C(Predicted)
• 密度：
  1.82±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 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：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H319
• 储存条件：
  -20°C 冰箱

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H319: Causes serious eye irritation
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: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine
CAS number: 84955-31-7

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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: C6H5ClN4
Molecular weight: 168.6

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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.

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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

2-氨基-4-氯吡咯并[2,3-D]嘧啶是医药和化工制备中的常用中间体。吡咯[2,3-d]嘧啶化合物是一种重要的药物中间体，不仅在止痛和抗癌方面具有独特疗效，还能治疗风湿性关节炎、牛皮癣、糖尿病等疑难杂症。因此，这类化合物的应用前景广泛，近年来备受关注。

制备

目前合成吡咯[2,3-d]嘧啶化合物的方法主要有以下三种：以嘧啶化合物为底物构建吡咯环、以吡咯为母体构建嘧啶环和同时构建两种杂环。2-氨基-4-氯吡咯并[2,3-D]嘧啶的合成起始于2,6-二氨基-6-羟基嘧啶，经过关环、还原、氯代等步骤制备而成。其合成路线图如下：


反应信息

• 作为反应物：
  描述：

  2-氨基-4-氯吡咯并[2,3-d]嘧啶 在 copper(l) iodide 、 N,O-双三甲硅基乙酰胺 、 10% Pd/C 、 potassium carbonate 、 三苯基膦 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.67h， 生成 4-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)but-3-yn-1-ol
  参考文献：
  名称：

  EC144 Is a Potent Inhibitor of the Heat Shock Protein 90

  摘要：

  Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90 alpha binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

  DOI：

  10.1021/jm300810x
• 作为产物：
  描述：

  2,6-diamino-5-(3,3-diethoxyethyl)pyrimidin-4(3H)-one 在 盐酸 、 三氯氧磷 作用下， 反应 7.0h， 生成 2-氨基-4-氯吡咯并[2,3-d]嘧啶
  参考文献：
  名称：

  Tsytovich, A. V.; Shamshin, D. V.; Burkovskii, V. B., Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 11, p. 756 - 761

  摘要：

  DOI：
• 作为试剂：
  描述：

  2-氨基-4-羟基吡咯并[2,3-d]嘧啶 、 三氯氧磷 在 water ice 、 二氯甲烷 、 silica gel 、 methanol-dichloromethane 、 2-氨基-4-氯吡咯并[2,3-d]嘧啶 作用下， 反应 5.0h， 以This resulted in 0.3 g (53%) of 4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine as a light yellow solid的产率得到2-氨基-4-氯吡咯并[2,3-d]嘧啶
  参考文献：
  名称：

  IRAK INHIBITORS AND USES THEREOF

  摘要：

  本发明提供了呋喃基和吡咯基嘧啶和吡啶化合物，它们的组成物以及使用它们的方法。

  公开号：

  US20140018361A1

文献信息

• [EN] PYRROLOPYRIMIDINES AS FAK AND ALK INHIBITERS FOR TREATMENT OF CANCERS AND OTHER DISEASES<br/>[FR] PYRROLOPYRIMIDINES À TITRE D'INHIBITEURS DE FAK ET D'ALK POUR LE TRAITEMENT DES CANCERS ET AUTRES MALADIES
  申请人：ABBOTT LAB

  公开号：WO2012045195A1

  公开（公告）日：2012-04-12

  Disclosed are compounds which inhibit the activity of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK), compositions containing the compounds, and methods of treating diseases during which FAK and ALK are expressed. The diseases are, for example, cancers.

  揭示了抑制焦点粘附激酶（FAK）和间变性淋巴瘤激酶（ALK）活性的化合物，含有这些化合物的组合物，以及治疗在其中FAK和ALK表达的疾病的方法。这些疾病例如包括癌症。
• Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
  申请人：——

  公开号：US20020147160A1

  公开（公告）日：2002-10-10

  The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

  本发明提供了核苷化合物及其某些衍生物，这些衍生物是RNA依赖性RNA病毒聚合酶的抑制剂。这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用于治疗RNA依赖性RNA病毒感染。它们特别适用于作为丙型肝炎病毒（HCV）NS5B聚合酶的抑制剂，作为HCV复制的抑制剂，以及/或用于治疗丙型肝炎感染。本发明还描述了包含这种核苷化合物的药物组合物，单独使用或与其他对RNA依赖性RNA病毒感染，特别是HCV感染有效的制剂组合使用。还公开了使用本发明的核苷化合物抑制RNA依赖性RNA聚合酶、抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。
• 7-去氮-7-卤素鸟嘌呤核苷的合成方法
  申请人：上海交通大学

  公开号：CN103819523B

  公开（公告）日：2016-02-10

  本发明公开了一种7-去氮-7-卤素鸟嘌呤核苷的合成方法；所述方法包括如下步骤：式(III)化合物在碱性条件下去保护基得式(IV1)或(IV2)化合物；进一步去甲基得式(I)化合物，即所述7-去氮-7-卤素鸟嘌呤核苷；其中，R1为H或OH，R2为I、Br或Cl，R3为H或本发明合成的7-去氮-7-卤素-鸟嘌呤核苷是在DNA测序、标记、延伸等生物学领域广泛使用的基本原料，目前其销售价格很高，且合成方法复杂，难以控制；而本发明的合成方法所需原料简单易得，合成过程均为常规化学反应，可用于大规模推广使用。
• N4-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d]pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation
  作者：Aleem Gangjee、Nilesh Zaware、Sudhir Raghavan、Jie Yang、Jessica E. Thorpe、Michael A. Ihnat

  DOI：10.1016/j.bmc.2012.01.029

  日期：2012.4

  With the goal of developing multitargeted receptor tyrosine kinase inhibitors that display potent inhibition against PDGFRβ and VEGFR-2 we designed and synthesized eleven N4-(3-bromophenyl)-7-(substitutedbenzyl) pyrrolo[2,3-d]pyrimidines 9a–19a. These compounds were obtained from the key intermediate N4-(3-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine 29. Various arylmethyl groups were regiospecifically

  为了开发对 PDGFR β和 VEGFR-2 具有有效抑制作用的多靶点受体酪氨酸激酶抑制剂，我们设计并合成了 11 种N 4 -(3-溴苯基)-7-(取代苄基)吡咯并[2,3- d ]嘧啶9a – 19a . 这些化合物是从关键中间体N 4 -(3-溴苯基)-7 H-吡咯并[2,3- d ]嘧啶-2,4-二胺29获得的。通过氢化钠诱导的取代芳基甲基卤化物的烷基化，将各种芳基甲基基团区域特异性连接在29的N7处。化合物11a和19a是PDGFRβ和VEGFR-2的有效双重抑制剂。在 COLO-205 中，体内肿瘤小鼠模型11a表现出对肿瘤生长、转移和肿瘤血管生成的抑制作用，优于或相当于标准化合物 TSU-68 (SU6668, 8 )。
• Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2′-C-methyl-6-O-methyl guanosine nucleoside and l-Alanine ester phosphoramidates
  作者：Claire Bourdin、Christopher McGuigan、Andrea Brancale、Stanley Chamberlain、John Vernachio、Jeff Hutchins、Elena Gorovits、Alexander Kolykhalov、Jerry Muhammad、Joseph Patti、Geoffrey Henson、Blair Bleiman、K. Dawn Bryant、Babita Ganguly、Damound Hunley、Aleksandr Obikhod、C. Robin Walters、Jin Wang、Changalvala V.S. Ramamurty、Srinivas K. Battina、C. Srivinas Rao

  DOI：10.1016/j.bmcl.2012.12.004

  日期：2013.4

  HCV inhibitors now in clinical trials. In this Letter, we report the synthesis and biological evaluation of 2′-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives. In contrast to prior studies, removal of the N-7 of the nucleobase entirely negates anti-HCV activity compared to the 2′-C-methyl-6-O-methylguanosine analogues. To understand better this significant loss of activity, enzymatic assays

  已知7-脱氮嘌呤具有广泛的抗病毒活性，但是2'- C-甲基鸟苷类似物显示差的细胞渗透和有限的磷酸化，因此不是丙型肝炎病毒（HCV）复制的有效抑制剂。我们先前曾报道6- O-甲基实体作为增加鸟嘌呤核苷亲脂性的前药部分，并且ProTide方法应用于2' - C-甲基-6- O-甲基鸟苷已导致有效的HCV抑制剂正在临床试验中。在这封信中，我们报告了2'- C-甲基-6- O的合成和生物学评价-甲基-7-脱氮鸟苷和ProTide衍生物。与先前的研究相反，与2' - C-甲基-6- O-甲基鸟苷类似物相比，去除核碱基的N-7完全消除了抗HCV活性。为了更好地了解这种显着的活性丧失，进行了酶促测定和分子建模，结果表明2'- C-甲基-6- O-甲基-7-脱氮鸟苷和相关ProTides不能充当游离核苷酸的有效前药，与亲代鸟嘌呤类似物的情况形成鲜明对比。

表征谱图