4-ethynylpiperidine

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3R,3aR,6R,6aR)-6-((5-(4-bromophenyl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (25 mg, 0.055 mmol), 4-ethynylpiperidine (10.5 mg, 0.072 mmol), copper (I) iodide (2.1 mg, 0.011 mmol), chloro(tri-tert-butyl)-2-[-(2′amino-1,1′-biphenyl)]palladium (II) (5.7 mg, 0.011 mmol, prepared by a procedure analogous to procedures described in J. AM. CHEM. SOC. 2010, 132, 14073-14075), and cesium carbonate (54.0 mg, 0.166 mmol) were placed under nitrogen in dry, degassed toluene (138 μl) and dimethylacetamide (138 μl). The mixture was stirred at 50° C. for 2 hours. The resulting residue was diluted with dimethylformamide (0.7 mL), then filtered through a filter disc (0.45 micron). The material was purified by reverse phase HPLC purification using 0-100% acetonitrile in water over 10 minutes. The desired product fraction was concentrated under reduced pressure to afford the title compound as an off-white solid. LC-MS: calculated for C25H25ClN4O4 480.16 observed m/e: 481.14 (M+H)+ (Rt 1.43/4 min). 1H NMR δ (ppm) (CD3OD): 7.80 (1H, s), 7.62 (2H, d, J=8.5 Hz), 7.49 (2H, d, J=8.5 Hz), 5.53 (1H, m), 4.95 (1H, t, J=5.5 Hz), 4.46 (1H, t, J=5.0 Hz), 4.27 (1H, m), 4.15 (1H, dd, J=9.5, 6.0 Hz), 4.09 (1H, dd, J=10.0, 4.9 Hz), 3.88 (1H, dd, J=8.0, 7.0 Hz), 3.58 (1H, t, J=8.5 Hz), 3.42 (2H, m), 3.18 (2H, m), 3.09 (1H, m), 2.17 (2H, m), 1.96 (2H, m) in dry degassed toluene (138 μl) and dimethylacetamide (138 μl) The resulting residue was diluted with dimethylformamide (0.7 mL) filtered through a filter disc (0.45 micron) The material was purified by reverse phase HPLC purification over 10 minutes The desired product fraction was concentrated under reduced pressure