Application of 2-amino-4-fluorotrifluorotoluene_Kain Industrial Additive

Background and overview^[1]

2-Amino-4-fluorotrifluorotoluene can be used as a pharmaceutical synthesis intermediate. If you inhale 2-amino-4-fluorotrifluorotoluene, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if In case of eye contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Apply ^[1]

2-Amino-4-fluorotrifluorotoluene can be used as a pharmaceutical synthesis intermediate. For example, the following compounds are synthesized:

Step 1: Preparation of 6-(aminomethyl)-N-(5-fluoro-2-(trifluoromethyl)phenyl)pyridin-3-amine

A mixture of 0.2mmol 2-amino-4-fluorotrifluorotoluene and 22mg (0.2mmol) potassium tert-butoxide in 99 ml_ DMSO was stirred at room temperature for 1 hour, then 24mg (0.2mmol) 2-cyano- 5-fluoropyridine, and the mixture was further stirred at 800°C overnight. Work-up: The reaction mixture was filtered through Alox B, washed with DMF and evaporated to dryness in vacuo. The residue was dissolved in 100 μl of methanolic ammonia solution and hydrogenated for 5 hours at 55° C. and 3 hours of hydrogen pressure using 20 mg of Raney nickel as a catalyst. The catalyst was then filtered off, the solvent was removed from the filtrate, and the crude product was purified by HPLC. Yield: 47% of theoretical value

Step 2: Pyrimidine-5-carboxylic acid N-(1-((5-(4-fluoro-2-(trifluoromethyl)phenylamino)pyridin-2-yl)-methylcarbamoyl) )-Cyclopropyl)amide Preparation

Dissolve 1.2mmol and 1-[(pyrimidine-5-carbonyl))-amino]-cyclopropane-carboxylic acid in 15mL tetrahydrofuran, add 0.5mL (3.6mmol) triethylamine, 433mg (1.35mmol) TBTU and 326 mg (1.2 mmol) 6-(aminomethyl)-N-(5-fluoro-2-(trifluoromethyl)phenyl)pyridin-3-amine. The mixture was stirred at room temperature overnight, then concentrated to dryness and purified by HPLC.

Main reference materials

[1] WO2010097372 COMPOUNDS AS BRADYKININ B1 ANTAGONISTS