Methanol → N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (100 mg, 0.319 mmol) and N-(4-amino-2-chlorophenyl)acetamide (64.8 mg, 0.351 mmol, Aldrich) in THF (5 mL), argon was bubbled in for 2 min and the tube was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF, 1 mL, 0.957 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was diluted with saturated NaHCO3 and extracted with EtOAc (3×).The organic extract was washed with satd. NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g) eluting with a gradient of 2% to 5% 2 M NH3.MeOH in DCM to give N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (120 mg, 0.251 mmol, 79% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.84 (s, 1H); 9.74 (dd, J=7.92, 1.86 Hz, 1H); 9.47 (s, 1H); 8.89 (s, 1H); 8.42 (dd, J=4.70, 1.76 Hz, 1H); 8.30 (d, J=2.35 Hz, 1H); 7.55-7.63 (m, 1H); 7.45-7.54 (m, 1H); 7.08 (dd, J=7.82, 4.69 Hz, 1H); 5.85 (dd, J=10.95, 2.15 Hz, 1H); 4.01-4.10 (m, 1H); 3.72-3.85 (m, 1H); 2.92 (s, 3H); 2.24-2.39 (m, 1H); 2.08 (s, 3H); 1.96-2.05 (m, 2H); 1.73-1.91 (m, 1H); 1.56-1.70 (m, 2H). m/z (ESI, +ve ion) 478 (M+H)+.

Provenance & Evidence