3-chloro-4-(2-methoxyethoxy)aniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (0.1 g, 0.218 mmol) and 3-chloro-4-{[2-(methyloxy)ethyl]oxy}aniline (0.057 g, 0.283 mmol) were combined in a microwave safe reaction vessel. Ethylene glycol dimethyl ether (1.5 mL) and HCl (˜½ drop) were then added and the resulting mixture was heated in a microwave to 160° C. for 8 min. The reaction was then cooled to rt diluted with EtOAc (100 mL) and water (50 mL). The organic layer was separated, washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo onto silica gel. This was then purified via silica gel chromatography (EtOAc/Hexanes) to provide 55 mg of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1H), 9.53 (s, 1H), 8.83 (d, 1H), 8.42 (br m, 1H), 8.25 (d, 1H), 8.00 (s, 1H), 7.93 (s, 1H), 7.80 (d, 1H), 7.62-7.42 (m, 4H), 7.33 (d, 1H), 7.24 (m, 2H), 7.12 (m, 1H), 7.03 (d, 1H), 6.52 (d, 1H), 4.11 (m, 2H), 3.65 (m, 2H), 3.30 (s, 3H); HRMS: calc. C33H26N6O3F2 (M+H)+ 627.1723 found 627.1732. The reaction was then cooled to rt The organic layer was separated washed with brine (50 mL) dried over Na2SO4 filtered concentrated in vacuo onto silica gel This was then purified via silica gel chromatography (EtOAc/Hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-1-{[2-(methyloxy)ethyl]oxy}-4-nitrobenzene (1.0 g) was dissolved in a 1:1 solution of EtOAc and ethanol (30 mL). Pt/C (0.15 g of 10% by weight) was added and the resulting mixture was placed under 50 psi of H2 for 16 h. The reaction was then filtered through celite and the resulting organics were concentrated in vacuo to obtain 0.85 g of the compound. 1H NMR (300 MHz, DMSO-d6): δ 6.88 (d, 1H), 6.66 (m, 1H), 6.50 (m, 1H), 4.00 (m, 2H), 3.63 (m, 2H), 3.33 (s, 3H). The reaction was then filtered through celite the resulting organics were concentrated in vacuo