4-Aminoacetanilide → N-(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 4′-aminoacetanilide (69.0 mg, 0.460 mmol, Aldrich, St. Louis, Mo.) and 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (120 mg, 0.383 mmol) in THF (5 mL), Ar was bubbled in for 2 minutes and the reaction was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF, 1.2 mL, 1.2 mmol) was added dropwise and the solution was stirred at 0° C. for 1 h. After warming to room temperature, the reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (3×). The organic extracts were washed with brine and dried over Na2SO4. The solution was filtered and concentrated in vacuum. The crude material was purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (25 g), eluting with a gradient of 2% to 10% 2 M NH3/MeOH in CH2Cl2, to provide N-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (115 mg, 0.259 mmol, 67.7% yield) as a yellow solid. MS (ESI positive ion) m/z 444 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.68 (s, 1H); 9.86 (s, 1H); 9.72 (d, J=8.02 Hz, 1H); 8.86 (s, 1H); 8.34 (d, J=2.15 Hz, 1H); 7.75 (d, J=7.82 Hz, 2H); 7.56 (d, J=7.63 Hz, 2H); 6.98 (s, 1H); 5.84 (d, J=10.95 Hz, 1H); 3.92-4.22 (m, 1H); 3.64-3.87 (m, 1H); 2.90 (s, 3H); 2.30-2.33 (m, 1H); 2.03 (s, 3H); 1.99-2.01 (m, 2H); 1.79-1.82 (m, 1H); 1.48-1.71 (m, 2H).

Provenance & Evidence