5-(Trifluoromethyl)pyridine-2-carboxylic acid

Reference Example 2 (0150) Production Method of 5-(trifluoromethyl)pyridine-2-carboxylic acid ester (0151) A 100-mL autoclave was charged successively with 2-chloro-5-(trifluoromethyl)pyridine (24.55 g, 135.26 mmol), PdClTo a stirred solution of tert-butyl 4-aminopiperazine-l-carboxylate (315 mg, 1.5 mmol, 1.0 equiv) in DMF (05 mL) was added HATU (1140 mg, 3.0 mmol, 2.0 equiv) at RT and stirred for 10 minutes. Then 5~(trifuorome'hyl)picolinic acid (300 mg, 1 .5 mmol, 1.0 equiv) was added followed by the addition of DIPEA (0.8 mL, 4.5 mmol, 3.0 equiv). The resulting reaction mixture was allowed to stir at RT for overnight. Product formation was confirmed by LCMS. the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL c 2). The combined organic layer was washed with water (30mL), brine solution (30 mL c 2), dried over anhydrous sodium sulfate and concentrated under reduced pressure, to obtain tert-butyl 4-(5- (trifluoromethyl)picolinamido)piperazine-l-carboxylate (100 mg, 17 % Yield) as a brown solid. LCMS 375.1 [M+Hf; 'H NMR (400 MHz, DMSO-rfe) d 10.04 (s, 1 H), 9.00 (br s , 1 H), 8.93 (s, 1 H), 8.41 (d, .7=7.89 Hz, 1 H), 8.19 (d, .7=8.33 Hz, 1 H), 3.42 (br. s., 4 H), 2.87 - 2.94 (m, 4 H), 1.41 (d, .7=3.51 Hz, 9 H).A mixture containing CoCl26H2O (12.40 mg, 0.05 mmol), Htpc (9.50 mg, 0.05 mmol), and water (6 mL) was sealed in a 15-mL Teflon-lined stainless steel vessel and heatedat 413 K for 3 days and then cooled to room temperature at a rate of 10 Kh1. Afterfiltration, red block crystals were collected and washed with distilled water severaltimes, then dried at room temperature. Yield: 4.96mg (40%, based on CoCl26H2O).Anal. Calcd (%) for C14H10CoF6N2O6 (molecular weight 475.17 gmol1): C, 35.39; H, 2.12; N, 5.90. Found (%): C, 35.54; H, 2.21; N, 5.98. IR (KBr, cm1): 3347 w, 1663 m, 1510 m, 1410 m, 1148w, 936 w, 820 w, 640 w, 473 w.

5-(Trifluoromethyl)pyridine-2-carboxylic acid is an intermediate used in the synthesis of β-secretase (BACE) inhibitors.

Molecular Weight:191.11
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:1
Exact Mass:191.01941286
Monoisotopic Mass:191.01941286
Topological Polar Surface Area:50.2
Heavy Atom Count:13
Complexity:204
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes