5-氰基-7-氮杂吲哚 | 517918-95-5

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 5-氰基-7-氮杂吲哚
• 英文名称: 1H-pyrrolo[2,3-b]pyridine-5-carbonitrile
• 英文别名: 5-cyano-7-azaindole
• CAS: 517918-95-5
• 化学式: C₈H₅N₃
• mdl: MFCD06659684
• 分子量: 143.148
• InChiKey: DRAQIXNADYAISI-UHFFFAOYSA-N

物化性质

• 熔点：
  225.1-225.2°C
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 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：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37
• 危险类别码：
  R22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险品运输编号：
  NONH for all modes of transport
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 危险性防范说明：
  P261,P305+P351+P338
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H302: Harmful if swallowed
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory 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: 1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile
CAS number: 517918-95-5

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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.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
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.

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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: C8H5N3
Molecular weight: 143.1

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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

5-氰基-7-氮杂吲哚是目前合成新型抗肿瘤新药—蛋白酶抑制剂类中常用的中间体，主要用于实验室研发过程和化工生产过程中。

制备

在500L反应釜中，依次加入5-溴-7-氮杂吲哚40Kg、N-甲基吡咯烷酮(NMP)200Kg以及氰化亚铜20Kg，在氮气氛围下，将体系缓慢升温至180℃并保温15小时。通过HPLC监测确保原料含量低于0.5％后停止反应，并将反应液冷却至约40℃。

随后，将反应液转移至3000L反应釜中，加入1600Kg乙酸乙酯进行稀释，使用5％氨水洗涤至接近无色，再用饱和食盐水洗涤并以无水硫酸钠干燥。过滤后浓缩得粗品5-氰基-7-氮杂吲哚。

向上述粗品中加入400Kg乙酸乙酯和4Kg活性炭，回流0.5小时后趁热压滤，使用100Kg热乙酸乙酯洗涤并合并滤液浓缩至约200L。冷却后析出固体，过滤得到目标产品5-氰基-7-氮杂吲哚23Kg，收率为79.3％，纯度为99.8％。

反应信息

• 作为反应物：
  描述：

  5-氰基-7-氮杂吲哚 在 氯化亚砜 、 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 34.0h， 生成 甲基1H-吡咯并[2,3-B]吡啶-5-甲酸酯
  参考文献：
  名称：

  氮杂吲哚异羟肟酸衍生物对幽门螺杆菌甲硫氨酸氨肽酶的选择性抑制：设计、合成、体外生化和结构研究

  摘要：

  甲硫氨酸氨肽酶 (MetAPs) 是一类重要的酶，可协同翻译去除起始甲硫氨酸。化学抑制或基因敲低对微生物来说是致命的，这表明它们可以用作抗生素靶点。然而，微生物和宿主 MetAP 之间的序列和结构相似性一直是鉴定选择性抑制剂的挑战。在这项研究中，我们分析了数千个 MetAP 序列并建立了酶 S1 口袋中的变异模式。基于这一知识，我们设计了一个包含 17 种氮杂吲哚基异羟肟酸衍生物的文库，与人类对应物相比，该文库选择性地抑制了幽门螺杆菌的 MetAP 。结构研究为选择性提供了分子基础。

  DOI：

  10.1016/j.bioorg.2021.105185
• 作为产物：
  描述：

  5-溴-7-氮杂吲哚 以96%的产率得到5-氰基-7-氮杂吲哚
  参考文献：
  名称：

  HETEROCYCLIC COMPOUND, APPLICATION THEREOF, AND COMPOSITION CONTAINING SAME

  摘要：

  由式XI表示的杂环化合物，其药用盐、溶剂合物，或其药用盐的溶剂合物，以及其用途和含有该化合物的组合物。该化合物在结构上是新颖的，并具有良好的STAT5抑制活性。

  公开号：

  EP3960736A1

文献信息

• [EN] HETEROARYL SUBSTITUTED AMINOPYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS D'AMINOPYRIDINE SUBSTITUÉS PAR HÉTÉROARYLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016210034A1

  公开（公告）日：2016-12-29

  Disclosed are compounds of Formula (I) or salts thereof, wherein HET is a heteroaryl selected from pyrrolo[2,3 b]pyridinyl, pyrrolo[2,3 d]pyrimidinyl, pyrazolo[3,4 b]pyridinyl, pyrazolo[3,4 d]pyrimidinyl, imidazolo[4,5 b]pyridinyl, and imidazolo[4,5 d]pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a nitrogen ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 2 Rb; A is pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxadiazolyl or dihydroisoxazolyl, each substituted with zero or 1 Ra; and R3, Ra, and Rb are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.

  公开的是Formula (I)的化合物或其盐，其中HET是从吡咯并[2,3 b]吡啶基、吡咯并[2,3 d]嘧啶基、吡唑并[3,4 b]吡啶基、吡唑并[3,4 d]嘧啶基、咪唑并[4,5 b]吡啶基和咪唑并[4,5 d]嘧啶基中选择的杂芳基，其中所述杂芳基通过所述杂芳基中的一个氮环原子连接到Formula (I)的化合物中的吡啶基，并且所述杂芳基被取代为零至2个Rb；A是吡唑基、咪唑基、三唑基、异噁唑基、噁二唑基或二氢异噁唑基，每个取代为零或1个Ra；R3、Ra和Rb在此处定义。还公开了使用这些化合物作为IRAK4调节剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓炎症和自身免疫疾病，或在癌症治疗中是有用的。
• MASP-2 INHIBITORS AND METHODS OF USE
  申请人：Omeros Corporation

  公开号：US20190367452A1

  公开（公告）日：2019-12-05

  The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.

  本公开提供了具有MASP-2抑制活性的化合物，这些化合物的组合物以及制造和使用这些化合物的方法。
• [EN] TRICYCLIC HETEROCYLIC DERIVATIVES<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES TRICYCLIQUES
  申请人：MERCK PATENT GMBH

  公开号：WO2017202748A1

  公开（公告）日：2017-11-30

  Compounds of the formula (I) in which R1 and R2 have the meanings indicated in Claim 1,are inhibitors of ATR, and can be employed for the treatment of diseases such as cancer.

  式(I)中R1和R2具有权利要求书中指示的含义，是ATR的抑制剂，可用于治疗癌症等疾病。
• [EN] PYRROLO[2,3-B]PYRIDINE CDK9 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRROLO[2,3-B]PYRIDINE CDK9 KINASE
  申请人：ABBVIE INC

  公开号：WO2014139328A1

  公开（公告）日：2014-09-18

  Disclosed are compounds of Formula (IIa), wherein R1, R2, R3A, R3B, R3C, R3D, R3E, and R4 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (IIa).

  公开的是Formula (IIa)的化合物，其中R1、R2、R3A、R3B、R3C、R3D、R3E和R4如规范中所定义，并且其药用盐。这些化合物可用作治疗疾病，包括癌症的药物。还提供了包含一个或多个Formula (IIa)化合物的药物组合物。
• 1,2,4-oxadiazole derivatives and their therapeutic use
  申请人：Laboratorios Almirall, S.A.

  公开号：EP2202232A1

  公开（公告）日：2010-06-30

  New derivatives of general formula (I), or pharmaceutically acceptable salts or N-oxides thereof wherein, A is selected from the group consisting of -N-, -O- and -S-; B and C are independently selected from the group consisting of-N- and -O-, with the proviso that at least two of A, B and C are nitrogen atoms; G1 is selected from the group consisting of -CH2-, -NH- and -O-; G2 is selected from the group consisting of -NR4- and -O-; R1 represents: ➢ a 8 to 10 membered bicyclic N-containing heteroaryl group optionally substituted with a C1-4 carboxyalkyl group or a C1-4 aminoalkyl group, ➢ a pyridyl group optionally substituted with one or more substituents selected from hydroxy groups, C1-4 alkyl groups, C1-4 carboxyalkyl groups, C1-4 haloalkyl groups, C1-4 alkoxy groups, amino groups, C1-4 aminoalkyl groups and C1-4 aminoalkoxy groups, ➢ a pyridone group substituted with one or more C1-4 alkyl groups; C1-4 haloalkyl groups or C1-4 aminoalkyl groups, or ➢ a group of formula: wherein: • Ra represents a hydrogen atom, a halogen atom, a C1-4 alkyl group, C3-4 cycloalkyl group or a -CF3 group; • Rb represents a hydrogen atom, a halogen atom, a C14 alkyl group, a -CF3 group or a C1-4 alkoxy group; • Rd represents a hydrogen atom, a C1-4 alkyl group or a C1-4 alkoxy group; • Rc represents: ○ a hydrogen atom, a C1-4 hydroxyalkyl group, a C1-4 aminoalkyl group which is optionally substituted with one or more substituents selected from halogen atoms, hydroxy groups and -CF3 groups; ○ a 4 to 6-membered saturated N-containing heterocyclic ring optionally substituted with a C1-2 carboxyalkyl group; ○ -(CH2)(0-4)-C(O)OR', -(CH2)(0-4)-C(O)NR'R", -(CH2)(0-4)-NHC(O)R", -S(O)2NR'R", -O-(CH2)(2-4)NR'R", -O-(CH2)(1-4)C(O)OR", -O-(CH2)(1-4)-C(O)NR'R", -(CH2)(0-4)-NR'R", -(CH2)(0-4)-CONHS(O)2R', -(CH2)(0-4)-NHS(O)2R' or -(CH2)(0-3)-N H-(CH2)(1-3)-(NH)(0-1)S(O)2R' wherein, ■ R' represents a hydrogen atom or a C1-4 alkyl group, ■ R" represents a hydrogen atom, a C1-4 alkyl group, a C3-4 cycloalkyl group, a C1-4 carboxyalkyl group, a C1-4 haloalkyl group, a C1-4 hydroxyalkyl group or a 6 membered, saturated N-containing heterocyclic ring, or ■ R' and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected from N and O, and which is optionally substituted with a carboxy or a C1-4 carboxyalkyl group, or Rc together with Rd form a C5-6 cycloalkyl group optionally substituted by a -NHRf group, wherein Rf is selected from the group consisting of a hydrogen atom and a carboxymethyl group; R2 and R3 are independently selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyl groups; and R4 is selected from the group consisting of a hydrogen atom, a phenyl group, a C3-4 cycloalkyl-C1-4 alkyl group, C1-4 aminoalkyl group, C1-4 haloalkyl group and a linear or branched C1-4 alkyl group which is optionally substituted by a phenyl or a pyridyl group.

  通用公式（I）的新衍生物，或其药用可接受盐或N-氧化物，其中， A选自-N-，-O-和-S-组成的群; B和C分别选自-N-和-O-组成的群，但至少有两个A，B和C是氮原子; G1选自-CH2-，-NH-和-O-组成的群; G2选自-NR4-和-O-组成的群; R1代表: ➢一个含氮杂环的8到10成员双环基团，可选择地取代为C1-4羧基烷基基团或C1-4氨基烷基基团， ➢一个吡啶基，可选择地取代为一个或多个取代基，所选取代基包括羟基、C1-4烷基基团、C1-4羧基烷基基团、C1-4卤代烷基基团、C1-4烷氧基团、氨基、C1-4氨基烷基基团和C1-4氨氧基团， ➢一个吡啶酮基，取代为一个或多个C1-4烷基基团；C1-4卤代烷基基团或C1-4氨基烷基基团，或 ➢一个公式的基团： 其中: • Ra代表氢原子、卤原子、C1-4烷基基团、C3-4环烷基基团或-CF3基团; • Rb代表氢原子、卤原子、C14烷基基团、-CF3基团或C1-4烷氧基团; • Rd代表氢原子、C1-4烷基基团或C1-4烷氧基团; • Rc代表: ○氢原子、C1-4羟基烷基基团、C1-4氨基烷基基团，可选择地取代为一个或多个取代基，所选取代基包括卤原子、羟基和-CF3基团; ○一个4到6成员饱和的含氮杂环环，可选择地取代为C1-2羧基烷基基团; ○-(CH2)(0-4)-C(O)OR'，-(CH2)(0-4)-C(O)NR'R"，-(CH2)(0-4)-NHC(O)R"，-S(O)2NR'R"，-O-(CH2)(2-4)NR'R"，-O-(CH2)(1-4)C(O)OR"，-O-(CH2)(1-4)-C(O)NR'R"，-(CH2)(0-4)-NR'R"，-(CH2)(0-4)-CONHS(O)2R'，-(CH2)(0-4)-NHS(O)2R'或-(CH2)(0-3)-N H-(CH2)(1-3)-(NH)(0-1)S(O)2R'其中， ■ R'代表氢原子或C1-4烷基基团， ■ R"代表氢原子、C1-4烷基基团、C3-4环烷基基团、C1-4羧基烷基基团、C1-4卤代烷基基团、C1-4羟基烷基基团或6成员饱和的含氮杂环环，或 ■ R'和R"与它们连接的氮原子一起形成一个4到6成员的杂环基团，该基团包含一个N原子和可选择地一个进一步选择自N和O的原子，并可选择地取代为羧基或C1-4羧基烷基基团， 或Rc与Rd一起形成一个可选择地由-NHRf基团取代的C5-6环烷基基团，其中Rf选自氢原子和羧甲基基团; R2和R3分别选自氢原子、卤原子和C1-4烷基基团;和 R4选自氢原子、苯基团、C3-4环烷基-C1-4烷基基团、C1-4氨基烷基基团、C1-4卤代烷基基团和可选择地由苯基或吡啶基取代的线性或支链C1-4烷基基团。