Water → HCID 178440674, compound

Participants

Reaction Conditions

Reaction Steps

3-tert-Butyl-isoxazole-5-carboxylic acid [4-amino-2-chloro-6-(2-trifluoromethyl-phenyl)-pyridin-3-yl]-amide (73.9 mg, 0.168 mmol, prepared as in the previous step) was dissolved in AcOH (1 mL) and the resulting solution was heated to 100° C. for 14 h. The resulting mixture was cooled to room temperature and poured into H2O (20 mL). The aqueous phase was extracted with DCM (3×10 mL) and the combined extracts were washed with sat NaHCO3 solution (20 mL). The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The residue was dissolved in POCl3 (1 mL) and heated for 16 h at 100° C. The resulting mixture was cooled to room temperature and poured onto ice (˜20 mL). After the POCl3 had been consumed, the precipitate was isolated by filtration and washed with H2O (2×20 mL). The solid was dissolved in DCM (25 mL) and the solution was dried over MgSO4 and filtered. The solvent was removed under reduced pressure and the crude product was chromatographed on a 24-g SiO2 pre-packed column eluting with 0:1-2:3 EtOAc/hexanes to yield 2-(3-tert-butyl-isoxazol-5-yl)-4-chloro-6-(2-trifluoromethyl-phenyl)-3H-imidazo[4,5-c]pyridine. 1H-NMR (400 MHz, CD3OD) δ: 7.84 (d, J=7.8 Hz, 1H), 7.69-7.77 (m, 1H), 7.62-7.68 (m, 2H), 7.59 (d, J=7.6 Hz, 1H), 7.30 (s, 1H), 1.43 (s, 9H). Mass Spectrum (LCMS, ESI pos.): Calculated for C20H16ClF3N4O: 421.1 (M+H); Measured: 421.1.

Provenance & Evidence