3-CHLORO-5-(TRIFLUOROMETHYL)BENZOIC ACID

To 282 mg (1 mmol) 6-{5-[(lS)-l-aminoethyl]-3-(trifluoromethyl)-lH-l, 2, 4-triazol-l-yl}nicotinonitrile, 231.5 mg (1 mmol) 3-chloro-5-(trifluoromethyl)-benzoic acid, 168 mg (1.30 mmol) N, N- diisopropylethylamine (Hunig's Base) in , V, N- d i m c t h y 1 f o r m a m i d c (DMF) (5 mL), 456.3 mg (1.20 mmol) [0-(7-azabenzotriazol-l-yl)-iV, iV, iV', iV'-tetramethyluronium-hexafluorophosphate] (HATU) was added, and the reaction mixture was stirred at room temperature overnight. The rection mixture was concentrated and the solid residue was treated with dichloromethane and then extracted with a saturated NaHCC solution and water. The organic phase was separated, dried and the solvent was evaporated. The remaining solid residue was chromatographed with a cyclohexane/acetone gradient on silica gel to afford after stir out with diethyl ether 226 mg (purity: 100 %; yield: 46.2 %) of the title compound. (0702) ESI mass [m/z]: 489.0 [M+H]+ (0703) H NMR (DMSO-de, 400 MHz) see NMR peaklist in table 1.5.6 g (45 mmol) L-alaninamide-hydrochloride, 10.05 (45 mmol) Add 212 mg (0.94 mmol) 3chloro-5-(trifluoromethyl)benzoic acid to a solution of 300 mg (0.85 mmol) of N-(pyridin-2-ylmethyl)-l-[l-(pyrimidin-2-yl)-lH-l, 2, 4-triazol-5-yl]ethanamine and 0.49 mL D1PEA in 30 mL EtOAc and stir the mixture at room temperature for 10 min. Add 1 mL T3P (50 wt. % in EtOAc) and stir at room temperature over night. Partitionate the mixture between water and EtOAc, separate the layers and wash the organic phase sequentially with water, aq. sat. NaHC03 and aq. sat. NH4CI. Dry over Na2S04, filter and concentrate under reduced pressure and purify the residue by preparative chromatography to provide the title compound 1-001 (54 mg). H-NMR (260 Kelvin): CD3CN, d see NMR peak list in Table 1. m/z [M+H]+ = 488.0

Molecular Weight:224.56
XLogP3:3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:223.9851915
Monoisotopic Mass:223.9851915
Topological Polar Surface Area:37.3
Heavy Atom Count:14
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes