A solution of 3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-ylamine (5.65 g, 30.0 mmol), 2-chloro-4,5-difluorobenzoic acid (6.93 g, 36.0 mmol), copper acetate (II) (0.545 g, 3.00 mmol) and potassium carbonate (4.15 g, 30.0 mmol) in N,N-dimethylformamide (30 mL) was heated under reflux under an argon atmosphere for 2 hours. The solution was allowed to cool to room temperature, and the reaction mixture was poured into water. The solution was made weakly acidic by the addition of 1N hydrochloric acid, and the resulting crude crystals were collected by filtration. The crystals were washed with water and air dried to give crude 4,5-difluoro-2-[[3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid (8.18 g, 79% yield). A solution of the compound (7.00 g, 20.3 mmol) in phosphorus oxychloride (9.73 mL, 104 mmol) was heated under reflux for 30 minutes. The reaction solution was allowed to cool to room temperature, and the residue was poured into iced water. The solution was neutralized by the addition of a sodium hydroxide solution, and the organic matter was extracted with chloroform. The extract was washed with saturated brine and water, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (chloroform) to give crude 4-chloro-6,7-difluoro-3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazolo[3,4-b]quinoline (2.70 g, 39% yield). To a solution of the compound (2.70 g, 36.0 mmol) in ethanol (120 mL), 6N hydrochloric acid (4 mL, 24.0 mmol) was added, and the mixture was heated under reflux for 3 hours. The reaction solution was allowed to cool to room temperature, and the resulting crystals were collected by filtration. The crystals were washed with ethanol, air dried and recrystallized from ethanol to give the title compound (1.68 g, 66% yield).
