Potassium Carbonate → HCID 67478938, compound

To a suspension of N-methyl-methanesulfonamide (0.61 g, 5.6 mmol) and potassium carbonate (1.0 g, 7.6 mmol) in Acetone (10 mL) was added 2-bromomethyl-benzonitrile (1.0 g, 5.1 mmol). The mixture was stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (30 mL), filtered through a plug of diatomaceous earth and evaporated to a yellow waxy solid (1.2 g). N-(2-Cyano-benzyl)-N-methyl-methanesulfonamide was isolated as yellow waxy solid (1.2 g, 100%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.73-7.63 (m, 3H), 7.44 (t, J=7.5 Hz, 1H), 4.56 (s, 2H), 2.95 (s, 3H), 2.84 (s, 3H). MS=225 (MH)+. 156 b) To a Paar bottle (250 mL) was added 10% palladium on carbon (50% wet)(1.1 g, 0.52 mmol) followed by a solution of N-(2-cyano-benzyl)-N-methyl-methanesulfonamide (1.28 g, 5.71 mmol) in 7 M of ammonia in methanol (50 mL). The mixture was degassed and charged with Hydrogen (50 psi). The mixture was shaken on a Paar apparatus until adsorption of hydrogen ceased. The mixture was degassed and kept under an atmosphere of nitrogen. The mixture was filtered through a plug of diatomaceous earth, rinsed with dichloromethane and evaporated. N-(2-Aminomethyl-benzyl)-N-methyl-methanesulfonamide was isolated as tan viscous oil (1.28 g, 98%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.41 (d, J=7.4 Hz, 1H), 7.36-7.24 (m, 3H), 4.40 (s, 2H), 3.99 (s, 2H), 2.89 (s, 3H), 2.72 (s, 3H). MS=229 (MH)+. 156 c) N-{2-[(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-benzyl}-N-methyl-methanesulfonamide was prepared 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (500.0 mg, 2.151 mmol) and N-(2-aminomethyl-benzyl)-N-methyl-methanesulfonamide (540.0 mg, 2.365 mmol) in a manner analogous to Example 2d. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.88 (d, J=6.7 Hz, 1H), 7.46-7.42 (m, 1H), 7.38-7.30 (m, 3H), 6.88 (t, J=7.6 Hz, 1H), 6.50 (d, J=7.9 Hz, 1H), 5.25-5.19 (m, 1H), 4.60 (d, J=5.5 Hz, 2H), 4.40 (s, 2H), 2.87 (s, 3H), 2.73 (s, 3H). MS=380 (MH)+. 156 d) N-Methyl-N-[2-({2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-benzyl]-methanesulfonamide was prepared from N-{2-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-benzyl}-N-methyl-methanesulfonamide (75.0 mg, 0.197 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (42.0 mg, 0.220 mmol) with 2,2′-Bis-dicyclohexylphosphanyl-biphenyl (22.0 mg, 0.0402 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a brown lyophilate as the trifluoroacetic acid salt (0.006 g, 6%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.50 (br s, 1H), 9.20 (s, 1H), 7.94 (d, J=6.7 Hz, 1H), 7.63 (d, J=9.1 Hz, 2H), 7.39-7.34 (m, 2H), 7.30-7.26 (m, 2H), 6.96 (d, J=8.8 Hz, 2H), 6.70 (t, J=7.4 Hz, 1H), 6.34 (br s, 1H), 6.24 (d, J=7.4 Hz, 1H), 4.62-4.59 (m, 2H), 4.40 (s, 2H), 3.71-3.65 (m, 2H), 3.23-3.13 (m, 2H), 3.03 (s, 3H), 2.92-2.82 (m, 4H), 2.65 (s, 3H). MS=535 (MH)+.

1. filtrationfiltered through a plug of diatomaceous earth
2. customevaporated to a yellow waxy solid (1.2 g)

ORD record

ord-0002744c82b2460eabb067afe84260d2

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501936B2