Lithium Hydroxide → 4-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid

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Reaction Steps

To a solution of 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester (1.50 g, 2.9 mmol) in THF (15 mL) was added aqueous LiOH [prepared from LiOH monohydrate (0.39 g, 9.0 mmol) and H2O (3.9 mL)] dropwise at room temperature. The mixture was stirred at room temperature for 21 hours. Additional aqueous LiOH solution [prepared from LiOH monohydrate (0.25 g) and H2O (2.5 mL)] was added at room temperature. The mixture was mixture was stirred at room temperature for 24 hours, and then evaporated. The aqueous mixture was diluted with 50 mL of H2O, washed with AcOEt, and treated with active charcoal. The mixture was filtered and the filtrate was carefully acidified to pH 4-5 with 1N HCl under stirring. The mixture (including oily precipitate) was sonicated for 1 hour and stirred at room temperature for 1 hour to give pale yellow solid. The resulting solid was collected by filtration, washed with H2O, and dried at 60° C. overnight under reduced pressure to give the title compound as pale yellow crystal (1.36 g, 93%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.48 (s, 9H), 2.68 (s, 3H), 6.93 (d, J=8.5 Hz, 1H), 7.37 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.57 (d, J=8.5 Hz, 1H), 7.75 (br-d, J=8.5 Hz, 1H), 7.89 (br-s, 1H), 8.58 (s, 1H), 8.80 (d, J=8.5 Hz, 1H), 9.62 (s, 1H), 10.15 (s, 1H), 12.97 (br-s, 1H)

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