Dimethylformamide → N-(3-Chloro-6-fluoro-1H-indazol-5-yl)-4-[2-fluoro-4-(trifluoro-methyl)phenyl]-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamide

Participants

Reaction Steps

The product from Example 21, Step 2 (1.0 g, 3.152 mmol, 1.0 equiv) and oxalyl chloride (330 μL, 3.783 mmol, 1.2 equiv) in CH2Cl2 (12.5 mL) with catalytic DMF (20 μL) was stirred at room temperature for 45 minutes. The reaction mixture was concentrated en vacuo and half was redissolved in CH2Cl2 (5 mL). This solution was added dropwise over 5 minutes to a solution of the product from Example 39, step 2 (322 mg, 1.733 mmol, 1.1 equiv) in pyridine (4 mL) at −20° C. The reaction mixture was slowly warmed to room temperature over 3 hours. The reaction mixture was diluted with EtOAc and 1N HCl. The phases were separated, and the organic phase was washed twice with 1N HCl, once with satd. NaHCO3, and once with satd. NaCl. The organic phase was concentrated en vacuo. The residue was purified by flash chromatography (0-80% EtOAc in Hexanes) and further purified by reverse-phase HPLC (20-90% CH3CN/H2O, 0.1TFA over 13 minutes, retention time 8.11 min) to provide 60 mg (8%) of the title compound as a white solid. MS (ES+) m/e 485 [M+H]+

Provenance & Evidence