Water → HCID 178440674, compound

Temperature

100 °C

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.

1. temperatureThe resulting mixture was cooled to room temperature
2. extractionThe aqueous phase was extracted with DCM (3×10 mL)
3. washthe combined extracts were washed with sat NaHCO3 solution (20 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. customthe solvent was removed under reduced pressure
7. dissolutionThe residue was dissolved in POCl3 (1 mL)
8. temperatureheated for 16 h at 100° C
9. temperatureThe resulting mixture was cooled to room temperature
10. additionpoured onto ice (˜20 mL)
11. customAfter the POCl3 had been consumed
12. customthe precipitate was isolated by filtration
13. washwashed with H2O (2×20 mL)
14. dissolutionThe solid was dissolved in DCM (25 mL)
15. dry with materialthe solution was dried over MgSO4
16. filtrationfiltered
17. customThe solvent was removed under reduced pressure
18. customthe crude product was chromatographed on a 24-g SiO2 pre-packed column
19. washeluting with 0:1-2:3 EtOAc/hexanes

ORD record

ord-f70dd0f5f9084b17b1f6e0b99983e9d5

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680098B2