100491-29-0

105152-47-4

100491-29-0

(1) 250 mg of phosphoryl chloride was slowly added dropwise to 4 mL of N,N-dimethylformamide followed by 200 mg of 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]ethyl acetate under cooling conditions in an ice bath and stirred for 10 min keeping the same temperature. Next, ethyl acetate was added to the reaction mixture. The reaction system was warmed up to 50-60°C for 3.5 hours. Upon completion of the reaction, the mixture was poured into 50 mL of ice water and extracted by adding 20 mL of chloroform, the organic layer was separated, washed with 20 mL of water and subsequently dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure, 5 mL of ether was added to the residue, and the crystals were collected by filtration to afford 150 mg (72.2% yield) of ethyl 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-diazanaphthalene-3-carboxylate, melting point 217-220 °C. The solvent was concentrated under reduced pressure. Crystals with melting points of 219-221°C were obtained by recrystallization from acetone-methanol solvent mixture (1:1, v/v). Elemental analysis (C17H10N2O3ClF3) Calculated values (%): C, 53.35; H, 2.63; N, 7.32. Measured values (%): C, 53.61; H, 2.47; N, 6.96.