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0 °C

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid (2.5 g, 6.19 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.138 g, 7.43 mmol) and EDC (1.424 g, 7.43 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.620 g, 7.43 mmol) and after 30 min the mixture was cooled to 0° C. Then DIEA (3.23 mL, 18.57 mmol) was added. The reaction mixture was stirred at the room temperature for 24 hr. Water (100 mL) followed by acetic acid (1 mL) were added and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and condensed. The resulting oil was purified by flash column chromatography on silica gel (2:1 DCM:EtOAc). 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluoro-N-(methyloxy)benzamide (1 g, 2.195 mmol, 35.5% yield) was isolated as a yellow foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.28 (d, J=6.57 Hz, 6 H) 2.11 (s, 3 H) 3.71 (s, 3 H) 4.41 (quin, J=6.51 Hz, 1 H) 5.97 (s, 1 H) 6.74 (s, 1 H) 6.87-7.06 (m, 1 H) 7.39 (dd, J=11.37, 2.53 Hz, 1 H) 7.66 (dd, J=8.46, 6.69 Hz, 1 H) 8.03 (s, 1 H) 8.57 (s, 1 H) 9.96 (br. s., 1 H) 11.98 (br. s., 1 H); HPLC Rt=2.36 min, MS (ESI): 433.3 [M+H]+.

1. stirringThe reaction mixture was stirred at the room temperature for 24 hr
2. additionwere added
3. extractionthe solution extracted with 2×50 ml of ethyl acetate
4. washThe organic layer was washed with 2×50 ml
5. dry with materialdried over MgSO4 and condensed
6. customThe resulting oil was purified by flash column chromatography on silica gel (2:1 DCM:EtOAc)