3-氟-4-(4-甲基-1-哌嗪基)苯胺 | 221198-99-8

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 3-氟-4-(4-甲基-1-哌嗪基)苯胺
• 中文别名: 3-氟-4-(4-甲基哌嗪基)苯胺
• 英文名称: 1-(2-fluoro-4-aminophenyl)-4-methylpiperazine
• 英文别名: 3-fluoro-4-(4-methylpiperazin-1-yl)aniline；3-fluoro-4-(4-methyl-1-piperazinyl)benzenamine
• CAS: 221198-99-8
• 化学式: C₁₁H₁₆FN₃
• mdl: MFCD05663793
• 分子量: 209.267
• InChiKey: GOPUCAPKOUZKPS-UHFFFAOYSA-N

物化性质

• 熔点：
  87-89
• 沸点：
  349.5±42.0 °C(Predicted)
• 密度：
  1.167±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Fluoro-4-(4-methylpiperazin-1-yl)aniline
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: 3-Fluoro-4-(4-methylpiperazin-1-yl)aniline
CAS number: 221198-99-8

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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: C11H16FN3
Molecular weight: 209.3

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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 fluoride.

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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

用途

3-氟-4-(4-甲基哌嗪基)苯胺可用作医药合成中间体。

危险处理

若吸入3-氟-4-(4-甲基哌嗪基)苯胺，请将其移至新鲜空气处；如皮肤接触，应脱去受污染的衣物，并用肥皂水和清水彻底清洗皮肤，如有不适，请就医；如眼睛接触到该物质，应翻开眼睑，使用流动清水或生理盐水冲洗，并立即就医；若误食，请立即漱口，禁止催吐，并尽快就医。

反应信息

• 作为反应物：
  描述：

  3-氟-4-(4-甲基-1-哌嗪基)苯胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium on activated charcoal 、 potassium carbonate 、 一水合肼 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 叔丁醇 为溶剂， 生成 艾维替尼
  参考文献：
  名称：

  吡咯并[2,3-d]嘧啶衍生物作为EGFR突变NSCLC细胞酪氨酸激酶抑制剂的合成及生物活性

  摘要：

  EGFR突变是NSCLC治疗中的一个持续挑战，需要不断更新EGFR TKI候选药物。吡咯并嘧啶是一组适用于定制药物开发的多功能支架。然而，在第三代共价 EGFR-TKI 领域中没有太多此类药效团的先例被研究。在此，一系列 pyrrolo[2,3- d] 通过优化的 Buchwald-Hartwig C-N 交叉偶联反应合成了能够以共价方式阻断突变 EGFR 活性的嘧啶衍生物。在分子和细胞水平上研究了它们的初步生物活性和相应的抑制机制途径。与对照化合物相比，几种化合物表现出增加的生物活性和增强的选择性。值得注意的是，与正常 HBE 细胞相比，化合物12i选择性地抑制具有 EGFR 激活突变的 HCC827 细胞，其功效提高了 493 倍。增强的选择性也通过激酶酶测定得到证实，测试化合物选择性抑制 T790 M 激活突变 EGFR（IC 50值 0.21 nM）与野生型 EGFR（IC 50值为

  DOI：

  10.1016/j.ejmech.2021.113711
• 作为产物：
  描述：

  3,4-二氟硝基苯 在 palladium on activated charcoal 、 potassium carbonate 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-氟-4-(4-甲基-1-哌嗪基)苯胺
  参考文献：
  名称：

  基于嘌呤支架的新型平滑配体作为治疗胰腺癌的潜在药物

  摘要：

  Hedgehog (Hh) 信号通路的异常激活与胰腺癌的发生和进展有关。因此，通过针对 G 蛋白偶联受体 Smoothened (SMO) 的抑制剂阻断 Hh 通路已被认为是治疗这种癌症的治疗靶点。在我们之前的工作中，我们获得了一种基于嘌呤支架（化合物）的新SMO配体，它在几种癌细胞系中表现出有趣的抗肿瘤活性。在这项工作中，我们报告了 17 种新嘌呤衍生物的设计和合成，其中一些衍生物对 Mia-PaCa-2（Hh 依赖性胰腺癌细胞系）表现出高细胞毒性作用，而对非肿瘤性 HEK-293 细胞则表现出低毒性。与吉西他滨，如 、 和 （IC = 4.56、4.11 和 3.08 μM，分别）。其中两种嘌呤还通过 NanoBRET 测定显示出与 SMO 结合的能力（p = 5.17 和 5.01），与化合物具有更高的亲和力（p = 1.51）。此外，对接研究提供了嘌呤取代模式与 SMO 亲和力相关的见解。最后，使用基于

  DOI：

  10.1016/j.bioorg.2024.107681
• 作为试剂：
  描述：

  3-氟-4-(4-甲基-1-哌嗪基)苯胺 、 2-chloro-4-(3-nitrophenoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-D]pyrimidine 在 3-氟-4-(4-甲基-1-哌嗪基)苯胺 作用下， 生成 N-(3-fluoro-4- (4-methylpiperazin-1-yl)phenyl)-4-(3-nitrophenoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-D]pyrimidin-2-amine
  参考文献：
  名称：

  NOVEL PYRROLOPYRIMIDINE COMPOUNDS AS INHIBITORS OF PROTEIN KINASES

  摘要：

  本发明涉及某些吡咯吡嗪衍生物、包含它们的药物组合物以及使用它们的方法，包括用于治疗增殖障碍和与激酶调节失调相关的其他疾病的方法（例如，但不限于，EGFR（包括HER）、Alk、PDGFR、BLK、BMX/ETK、BTK、FLT3（D835Y）、ITK、JAK1、JAK2、JAK3、TEC和TXK）和/或相应途径的方法。

  公开号：

  US20150210702A1

文献信息

• [EN] PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS<br/>[FR] PYRROLOTRIAZINES EN TANT QU'INHIBITEURS D'ALK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2010071885A1

  公开（公告）日：2010-06-24

  The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了一种式（I）的化合物或其盐形式，其中Q1、Q2、Q3和Q4如本文所定义。式（I）的化合物具有ALK和/或JAK2抑制活性，并可用于治疗增殖性疾病。
• [EN] TETRAHYDROBENZOFURO[2,3-C]PYRIDINE AND BETA-CARBOLINE COMPOUNDS FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES<br/>[FR] COMPOSÉS DE TÉTRAHYDROBENZOFURO[2,3-C]PYRIDINE ET DE BÊTA-CARBOLINE POUR LE TRAITEMENT, LE SOULAGEMENT OU LA PRÉVENTION DE TROUBLES ASSOCIÉS À DES AGRÉGATS DE PROTÉINE TAU
  申请人：AC IMMUNE SA

  公开号：WO2019233883A1

  公开（公告）日：2019-12-12

  The present invention relates to novel compounds of formula (I) that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

  本发明涉及一种可以用于治疗、缓解或预防与Tau（微管相关单元）蛋白聚集相关的一组疾病和异常的新化合物（I）的公式。这些疾病和异常包括但不限于神经原纤维缠结（NFTs），如阿尔茨海默病（AD）。
• [EN] PYRIMIDOPYRIMIDOINDAZOLE DERIVATIVE<br/>[FR] DÉRIVÉ DE PYRIMIDO-PYRIMIDO-INDAZOLE
  申请人：BANYU PHARMA CO LTD

  公开号：WO2010098367A1

  公开（公告）日：2010-09-02

  The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a):; R1 means a -(C=O)aOb(C1-C6)alkyl group, a -(C=O)aOb(C2-C6)alkenyl group, a -(C=O)aOb(C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R2 and R3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a -(C=O)aOb(C1-C6)alkyl group or a group of -(C=O)aN(R1e)R2e; R4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.

  这项发明是为了提供一种新型的抗癌药物或增敏剂，用于癌症化疗或放疗。通式(I)的化合物：其中A表示芳基或杂环基，或者是式(a)的基团；R1表示-(C=O)aOb(C1-C6)烷基、-(C=O)aOb(C2-C6)烯基、-(C=O)aOb(C3-C6)环烷基、芳基或杂环基；R2和R3各自表示氢原子、卤素原子、羟基、羧基、-(C=O)aOb(C1-C6)烷基或-(C=O)aN(R1e)R2e的基团；R4表示氢原子或(C1-C6)烷基等，具有优异的Wee1激酶抑制作用，因此在医学领域特别是各种癌症治疗领域中非常有用。
• [EN] 2-AMINO-4-HYDROXY-5-PYRIMIDINECARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF T CELL ACTIVATION FOR THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] DERIVES DE 2-AMINO-4-HYDROXY-5-PYRIMIDINOCARBOXAMIDE ET COMPOSES ASSOCIES SERVANT D'INHIBITEURS DE L'ACTIVATION DES LYMPHOCYTES T POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：AMGEN INC

  公开号：WO2005009443A1

  公开（公告）日：2005-02-03

  The present invention relates to pyrimidine or pyridine carboxamides or pharmaceutically-acceptable salts thereof. Also included is a method of treatment of inflammation, inhibition of T cell activation and proliferation, arthritis, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, organ transplant, acute transplant or heterograft or homograft rejection, transplantation tolerance induction, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease, including ulcerative colitis, Crohn's disease, lupus, contact hypersensitivity, delayed-type hypersensitivity, and gluten-sensitive enteropathy, type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, glomerulonephritis, serum sickness, uticaria, allergic diseases, asthma, hayfever, allergic rhinitis, scleracielma, mycosis fungoides, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, atopic dermatitis, colon carcinoma or thymoma in a mammal comprising administering a therapeutically-effective amount a compound as described above.

  本发明涉及嘧啶或吡啶甲酰胺或其药用可接受的盐。还包括一种治疗炎症、抑制T细胞激活和增殖、关节炎、类风湿性关节炎、银屑病关节炎、骨关节炎、器官移植、急性移植或异体移植或同种异体移植排斥、移植耐受性诱导、缺血或再灌注损伤、心肌梗死、中风、多发性硬化症、炎症性肠病，包括溃疡性结肠炎、克罗恩病、狼疮、接触超敏反应、迟发型超敏反应和谷蛋白敏感性肠病、1型糖尿病、银屑病、接触性皮炎、桥本甲状腺炎、舍格伦综合征、自身免疫性甲状腺功能亢进、阿狄森病、自身免疫多腺体病、自身免疫性脱发、恶性贫血、白癜风、自身免疫性垂体功能减退、吉兰-巴雷综合征、肾小球肾炎、血清病、荨麻疹、过敏性疾病、哮喘、花粉症、过敏性鼻炎、硬皮病、真菌病、皮肌炎、斑秃、慢性日光性皮炎、湿疹、贝赫切特病、掌跖脓疱病、脓皮病、塞扎里综合征、特应性皮炎、系统性硬化病、硬皮病、特应性皮炎、结肠癌或胸腺瘤的方法，包括施用如上所述的化合物的治疗有效量。
• [EN] FURO[3,2-d]PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSÉS DE FURO[3,2-D]PYRIMIDINE
  申请人：ABBOTT LAB

  公开号：WO2012048222A1

  公开（公告）日：2012-04-12

  The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

  本发明涉及式(I)的新化合物、药用可接受的盐、生物活性代谢物、前药、外消旋混合物、对映异构体、非对映异构体、溶剂合物和水合物，其中变量如本文所述定义。式(I)的化合物作为激酶抑制剂是有用的，因此可用于治疗某些状况和疾病，特别是炎症状况和疾病以及增殖性障碍和状况，例如癌症。