Water → HCID 44479178, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1) (6.00 g, 25.1 mmol) in dioxane (54 mL) was sequentially treated with water (7.2 mL), 2-fluoropyridin-3-ylboronic acid (Asymchem Laboratories, Inc., Morrisville, N.C.) (5.31 g, 37.7 mmol), sodium carbonate monohydrate (9.35 g, 75.4 mmol) and PdCl2 (dppf) (Strem Chemicals, Inc., Newburyport, Mass.) (0.616 g, 0.754 mmol). The stirred mixture was degassed (alternating vacuum/nitrogen) and heated under nitrogen at 100° C. for 10 h. The mixture was cooled and extracted into EtOAc (500 mL) from water (400 mL). The aqueous layer was extracted with EtOAc (200 mL) and the combined organic extracts were dried (MgSO4), filtered through Celite® (diatomaceous earth), and concentrated. The crude product was dissolved in a small volume of DCM and purified by flash chromatography (50% to 75% to 100% EtOAc/hexane) to give 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3.96 g, 53% yield) as an off-white solid. 1H NMR (400 MHz, d6-DMSO) δ 9.11 (s, 1H), 8.91 (s, 1H), 8.58 (m, 1H), 8.49 (s, 1H), 7.62 (m, 1H), 5.85 (d, 1H), 4.05 (m, 1H), 3.75 (m, 1H), 2.38 (m, 1H), 2.05 (m, 2H), 1.79 (m, 1H), 1.61 (m, 2H).

Provenance & Evidence