Potassium Acetate → 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Participants

Reaction Steps

A mixture of 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3) (531.6 mg, 2104 μmol), 2-fluoropyridin-3-ylboronic acid (Asymchem Laboratories, Inc., Morrisville, N.C.) (596 mg, 4230 μmol), potassium acetate (629 mg, 6409 μmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.) (37.2 mg, 52.6 μmol) under a N2 atmosphere was suspended in EtOH (5.0 mL) and H2O (1.0 mL), degassed, and heated at gentle reflux for 2 h. LCMS indicated the reaction was complete. The mixture was poured into saturated aqueous NaHCO3 and extracted into EtOAc. The EtOAc extracts were dried (MgSO4), concentrated and purified by flash chromatography (EtOAc) to give 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (519 mg, 78.7% yield) as a pale yellow oil which crystallized to give a white solid upon trituration with Et2O. 1H NMR (400 MHz, d6-DMSO) δ 8.79 (s, 1H); 8.46-8.53 (m, 1H); 8.43-8.46 (m, 1H); 7.55-7.62 (m, 1H); 5.78-5.85 (m, 1H); 4.00-4.08 (m, 1H); 3.70-3.80 (m, 1H); 2.78 (s, 3H); 2.26-2.40 (m, 1H); 1.95-2.06 (m, 2H); 1.72-1.87 (m, 1H); 1.56-1.67 (m, 2H). m/z (ESI, +ve) 314.0 (M+H)+.

Provenance & Evidence