2-甲基-3-(4-三氟甲氧基苯基)苯甲酸 | 1221722-10-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-甲基-3-(4-三氟甲氧基苯基)苯甲酸
• 中文别名: 2-甲基-4-三氟甲氧基-联苯-3-羧酸
• 英文名称: 2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxylic acid
• 英文别名: 2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxyIic acid；2-Methyl-3-(4-trifluoromethoxyphenyl)benzoic acid；2-methyl-3-[4-(trifluoromethoxy)phenyl]benzoic acid
• CAS: 1221722-10-6
• 化学式: C₁₅H₁₁F₃O₃
• 分子量: 296.246
• InChiKey: LNRROOUNLXDADK-UHFFFAOYSA-N

物化性质

• 熔点：
  113-115°C
• 沸点：
  374.0±42.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2918990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 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: 2-Methyl-3-(4-trifluoromethoxyphenyl)benzoic acid
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: 2-Methyl-3-(4-trifluoromethoxyphenyl)benzoic acid
CAS number: 1221722-10-6

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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, refrigerated.
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: C15H11F3O3
Molecular weight: 296.2

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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, 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

Sonidegib的主要循环代谢产物是M48。Sonidegib是一种刺猬途径抑制剂，而M48的 Tmax 达到60小时，比Sonidegib更长。

反应信息

• 作为反应物：
  描述：

  2-甲基-3-(4-三氟甲氧基苯基)苯甲酸 在 C₂₉H₃₉O₃P 、 C₄₈H₅₅ClN₂Pd 、 caesium carbonate 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 sonidegib
  参考文献：
  名称：

  一种大位阻氮杂环卡宾钯配合物及其制备方法与应用和基于其的索尼吉布的合成方法

  摘要：

  本发明属于有机合成及化学催化技术领域，公开了一种大位阻氮杂环卡宾钯配合物及其制备方法与其在室温空气条件下高效催化C‑N偶联反应的应用，和基于其的索尼吉布的合成方法。本发明的大位阻氮杂环卡宾钯配合物结构以二苯基咪唑为主配体骨架、官能团化烯丙基为辅助配体，通过在催化剂的金属中心旁边引入官能团化烯丙基作为辅助配体，具有显著提升的催化活性及稳定性，可应用于高效催化C‑N偶联反应，特别是可在室温条件下高效催化C‑N偶联反应，并能得到高达99％的收率。本发明还提供了一种以芳基/脂肪胺、芳基氯代物为反应物，钯催化体系催化下，室温下三步法合成索尼吉布的方法，本发明合成方法步骤少、总收率可高达74.5％。

  公开号：

  CN112209972A
• 作为产物：
  描述：

  methyl 2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 2-甲基-3-(4-三氟甲氧基苯基)苯甲酸
  参考文献：
  名称：

  发现含有联苯药效团的新型甲酰胺衍生物作为用于抗性管理的潜在杀菌剂

  摘要：

  天然产物是药物和农用化学品发现的主要来源之一。联苯骨架是许多天然产物中普遍存在的结构，具有广泛的生物活性。因此，为了研究天然联苯衍生物的潜在应用，基于天然联苯木脂素的活性药效团，设计并合成了一系列具有不同取代基模式的新型甲酰胺衍生物，及其对几种典型植物病原体的体外抗真菌活性。对卵菌纲、子囊菌纲、半知菌纲和担子菌纲进行了全面研究。这些极具潜力的化合物在针对灰葡萄孢的体内试验中得到了进一步测试。通过对黄瓜的研究，证明其在防治常见植物病害方面的实际应用，表明四种化合物可以有效防治多菌灵、芦他霉素和吡唑烷等抗性菌株。还利用分子对接、显微技术和无标记定量蛋白质组学分析探索了化合物B12对抗灰霉病的潜在作用模式。结果表明，化合物B12可能是一种潜在的用于控制灰霉病抗性的新型杀菌剂，它可以影响灰霉病菌的蛋白质合成。这些发现可为开发新型联苯衍生物作为潜在的绿色抗真菌剂提供一定的理论基础。

  DOI：

  10.1021/acs.jafc.3c04307

文献信息

• [EN] COMPOUNDS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016196879A1

  公开（公告）日：2016-12-08

  The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hh signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.

  本申请涉及包含酯基、硫酯基或肼基的化合物，以及合成这些化合物的方法。本申请还涉及含有这些化合物的药物组合物，以及通过向需要的受试者投药这些化合物和药物组合物来治疗由Hh信号通路介导的细胞增殖紊乱疾病，如癌症的方法。
• [EN] METABOLITES OF SONIDEGIB (LDE225)<br/>[FR] MÉTABOLITES DE SONIDEGIB (LDE225)
  申请人：NOVARTIS AG

  公开号：WO2015092720A1

  公开（公告）日：2015-06-25

  Provided herein are metabolites of N-(6-((2R,6S)-2,6-dimethylmorpholino)pyridin-3-yl)- 2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxamide (Sonidegib, LDE225) that modulate the activity of the Hedgehog signaling pathway and that are useful in the treatment of diseases related to activity of Hedgehog signaling pathway including, for example, cancers of the brain, muscle, skin, and prostate; medulloblastoma; pancreatic adenocarcinomas; and small-cell lung carcinomas.

  本文提供了N-(6-((2R,6S)-2,6-二甲基吗啡啉)吡啶-3-基)-2-甲基-4'-(三氟甲氧基)-[1,1'-联苯]-3-甲酰胺（索尼地吉，LDE225）的代谢产物，这些代谢产物调节Hedgehog信号通路的活性，并且在治疗与Hedgehog信号通路活性相关的疾病方面具有用处，包括例如大脑、肌肉、皮肤和前列腺癌、髓母细胞瘤、胰腺腺癌和小细胞肺癌。
• BIPHENYLCARBOXAMIDE DERIVATIVES AS HEDGEHOD PATHWAY MODULATORS
  申请人：Dierks Christine

  公开号：US20100197659A1

  公开（公告）日：2010-08-05

  The invention provides a method for modulating the activity of the hedgehog signaling pathway. In particular, the invention provides a method for inhibiting aberrant growth states resulting from phenotypes such as Ptc loss-of-function, hedgehog gain-of-function, smoothened gain-of-function or Gli gain-of-function, comprising contacting a cell with a sufficient amount of a compound of Formula I.

  该发明提供了一种调节刺猬信号通路活性的方法。具体来说，该发明提供了一种抑制由于Ptc功能丧失、刺猬功能增强、smoothened功能增强或Gli功能增强等表型引起的异常生长状态的方法，包括将细胞与化合物I式的足够量接触。
• An environmentally responsible 3-pot, 5-step synthesis of the antitumor agent sonidegib using ppm levels of Pd catalysis in water
  作者：Balaram S. Takale、Ruchita R. Thakore、Fan Yi Kong、Bruce H. Lipshutz

  DOI：10.1039/c9gc03495a

  日期：——

  industrial approach to sonidegib utilizes wasteful organic solvents and relies on high loadings of endangered Pd. This anticancer drug can now be synthesized in 5 steps using only 3 pots, along with ppm levels of a Pd catalyst, all done in water at ambient temperatures.

  Sonidegib的当前工业方法利用了浪费的有机溶剂，并依赖于高含量的濒临灭绝的Pd。该抗癌药现在只需3个罐，就可以在5个步骤中合成，而且ppm的Pd催化剂含量也可以在环境温度下在水中完成。
• 一种索尼吉布中间体及索尼吉布的制备方法
  申请人：新发药业有限公司

  公开号：CN109293649B

  公开（公告）日：2020-05-08

  本发明提供一种索尼吉布中间体及索尼吉布的制备方法。利用2‑氨基‑5‑硝基吡啶(Ⅱ)和R‑环氧丙烷(或S‑环氧丙烷)经环氧开环取代反应、然后经缩合反应制备索尼吉布关键中间体。然后索尼吉布关键中间体经催化加氢反应还原硝基得到(2S,6R)‑2,6‑二甲基‑4‑(5‑氨基吡啶‑2‑基)吗啉；2‑甲基‑4'‑(三氟甲氧基)‑[1,1'‑联苯]‑3‑甲酸和酰氯化试剂经酰氯化反应，然后和上述(2S,6R)‑2,6‑二甲基‑4‑(5‑氨基吡啶‑2‑基)吗啉经酰胺化反应制备索尼吉布(Ⅰ)。本发明方法所用原料价廉易得，成本低；制备步骤绿色安全简便、废水产生量小；产物收率和纯度高，利于工业化生产。