BENZOIC ACID, 4-CYANO-2-(TRIFLUOROMETHYL)-

Synthesis of (S)-4-cyano-N-(2-(2-cyano-4, 4-difluoropyrrolidin-1-yl)-2-oxoethyl)-2-(trifluoromethyl)benzamide To a stirred solution of 3-phenylisonicotinic acid (0.100 g, 0.46 mmol, 1.0 equiv) in DMF (10 mL), was added (S)-4, 4-difluoro-1-glycylpyrrolidine-2-carbonitrile hydrochloride (0.104 g, 0.46 mmol, 1.0 equiv), HOBt (0.068 g, 0.50 mmol, 1.1 equiv) and EDC.HCl (0.96 g, 0.50 mmol, 1.1 equiv). The mixture was allowed to stir at RT for 10 min. Triethyl amine (0.19 mL) was added and the mixture was allowed to stir at RT for overnight. Product formation was confirmed by LCMS and TLC. The reaction mixture was diluted with water and extracted with ethyl acetate (50 mL*2). Combined organic extracts were washed with water (20 mL*4), dried over anhydrous Na2SO4 and concentrated. The crude product obtained was purified by reversed phase HPLC to obtain (S)-4-cyano-N-(2-(2-cyano-4, 4-difluoropyrrolidin-1-yl)-2-oxoethyl)-2-(trifluoromethyl)benzamide (0.030 g, 17% Yield) as an off-white solid. LCMS 387.2 [M+H]+ 1H NMR (400 MHz, DMSO-d6) delta 9.05 (br. s., 1H), 8.40 (s, 1H), 8.28 (d, J=7.45 Hz, 1H), 7.78 (d, J=7.89 Hz, 1H), 5.12 (d, J=7.02 Hz, 1H), 4.27 (t, J=15.13 Hz, 1H), 4.01-4.21 (m, 3H), 2.72-2.99 (m, 3H).Preparation Example 9Trifluoroacetic acid (0.55 ml) was added to a solution oftert-butyl 4-cyano-2-(trifluoromethyl)benzoate (194 mg) in dichloromethane (2 ml) under ice cooling, followed by stirring at the temperature for one hour.It was warmed to room temperature and stirred for 17 hours.The reaction soltuion was concentrated under reduced pressure, a 1M aqueous sodium hydroxide solution (2 ml) was added thereto, followed by washing with diethyl ether. 1M hydrochloric acid (2 ml) was added to the aqueous layer, followed by extraction with ethyl acetate-methanol mixed solution (4:1).The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain c. 3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)-benzonitrile/3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide Prepared analogously to Example 1.a. from b.

Molecular Weight:215.13
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:1
Exact Mass:215.01941286
Monoisotopic Mass:215.01941286
Topological Polar Surface Area:61.1
Heavy Atom Count:15
Complexity:304
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes