Reaction Steps
To a round bottom flask was added 2-fluoro-benzonitrile (1.0 g, 8.2 mmol), N-Methyl-methanesulfonamide (1.0 g, 9.2 mmol), potassium carbonate (1.7 g, 12 mmol) and N,N-dimethylformamide (5 mL). The mixture was heated at 80° C. for 18 hours. The mixture was cooled to room temperature and water (50 mL) was added. The mixture was extracted with ethyl acetate (75 mL). The organic layer was washed with water (2×25 mL) and saturated aqueous sodium chloride (25 mL), dried over magnesium sulfate, filtered and evaporated to a waxy solid. The recovered solid was triturated with hexane, filtered and dried. N-(2-Cyano-phenyl)-N-methyl-methanesulfonamide was isolated as a pale yellow solid (0.74 g, 42%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.72 (d, J=7.7 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.47 (t, J=7.6 Hz, 1H), 3.40 (s, 3H), 3.13 (s, 3H). MS=211 (MH)+. 147b) N-(2-Aminomethyl-phenyl)-N-methyl-methanesulfonamide was prepared from N-(2-cyano-phenyl)-N-methyl-methanesulfonamide (0.75 g, 3.5 mmol) via hydrogenation using a Paar apparatus with 10% Palladium on Carbon (50% Wet)(5:45:50, palladium:carbon black:water, 0.75 g, 0.35 mmol) and hydrogen (50 psi) in 7M ammonia in methanol (50 mL). The mixture was shaken on a Paar apparatus until adsorption of hydrogen ceased. The mixture was degassed, backflushed with nitrogen, filtered through a plug of diatomaceous earth and rinsed with dichloromethane. The filtrate was evaporated under reduced pressure. Product isolated as a tan viscous oil (0.76 g, 100%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.54 (d, J=7.7 Hz, 1H), 7.38 (ddd, J=7.6, 0.9, 0.9 Hz, 1H), 7.30 (ddd, J=7.9, 1.3, 1.3 Hz, 1H), 7.24 (dd, J=7.9, 0.8 HZ, 1H), 4.00 (br s, 2H), 3.26 (s, 3H), 2.99 (s, 3H). MS=215 (MH)+. 147c) N-{2-[(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-phenyl}-N-methyl-methanesulfonamide was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.74 g, 3.2 mmol) and N-(2-aminomethyl-phenyl)-N-methyl-methanesulfonamide (0.76 g, 3.5 mmol) in a manner analogous to Example 2d. Product isolated as a white foam (0.847 g, 72%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.87 (d, J=6.5 Hz, 1H), 7.51-7.47 (m, 1H), 7.40-7.28 (m, 3H), 6.84 (t, J=7.5 Hz, 1H), 6.47 (d, J=7.8 Hz, 1H), 5.38 (t, J=5.4 Hz, 1H), 4.73 (d, J=6.1 Hz, 2H), 3.30 (s, 3H), 3.00 (s, 3H). MS=366 (MH)+. 147d) N-Methyl-N-[2-({2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-phenyl]-methanesulfonamide was prepared from N-{2-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-phenyl}-N-methyl-methanesulfonamide (75.0 mg, 0.205 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (44.0 mg, 0.230 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (23.0 mg, 0.0421 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.053 g, 50%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.79 (d, J=6.6 Hz, 1H), 7.55-7.50 (m, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.38-7.28 (m, 3H), 6.95 (d, J=8.8 Hz, 2H), 6.65 (t, J=7.5 Hz, 1H), 6.53 (s, 1H), 6.35 (d, J=7.7 Hz, 1H), 5.21 (t, J=6.0 Hz, 1H), 4.71 (d, J=6.1 Hz, 2H), 3.30 (s, 3H), 3.18-3.12 (m, 4H), 3.00 (s, 3H), 2.62-2.57 (m, 4H), 2.36 (s, 3H). MS=521 (MH)+.
