Potassium Acetate → tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.250 g, 0.989 mmol) and (R)-5-(1-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (0.489 g, 1.385 mmol) in dioxane (3 mL). Then A-Phos (0.070 g, 0.099 mmol), potassium acetate (0.291 g, 2.97 mmol) and water (0.5 mL) were added into the reaction mixture. The reaction mixture was stirred and heated in a CEM Explorer Microwave at 120° C. for 10 min (120 watts, Powermax feature on). The mixture was diluted with dichloromethane (10 mL), water (10 mL) and brine solution (5 mL). The organic layer was collected by extracting with dichloromethane (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to give the crude material as a tan oil. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica-gel column (40 g) eluting with 100% ethyl acetate to give tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate (0.400 g, 0.761 mmol, 77% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.20-8.29 (m, 3H) 5.78 (dd, J=10.37, 2.35 Hz, 1H) 3.76 (s, 1H) 3.55 (d, J=6.65 Hz, 1H) 3.34 (s, 5H) 2.82 (s, 3H) 2.33 (d, J=5.09 Hz, 5H) 1.95-2.13 (m, 3H) 1.56-1.81 (m, 5H) 1.33-1.40 (m, 9H). m/z (ESI, +ve ion) 526.2 (M+H)+.

Provenance & Evidence