Hydrochloric Acid → HCID 178482359, compound

Participants

Reaction Steps

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chloro-N-methylfuro[2,3-c]pyridin-7-amine (44.3 mg, 0.0961 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[2,3-c]pyridine (33.9 mg, 0.130 mmol), and Pd(PPh3)4 (12.8 mg, 0.0111 mmol) in 1,4-dioxane (0.5 mL) was charged with 1.0 M aqueous sodium carbonate (0.5 mL) and then irradiated in a microwave at 120° C. for 60 min. The reaction mixture was then charged with 4.0 M hydrochloric acid in 1,4-dioxane (0.6 mL) and stirred at rt for 30 min. The suspension was concentrated in vacuo. The residue was partitioned between a mixture of dichloromethane and aqueous sodium bicarbonate and the layers were separated. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by ISCO chromatography (2 to 10% 7 N ammonia/methanol:dichloromethane) afforded 30.1 mg (69%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.40 (s, 1H), 8.79 (s, 1H), 8.65 (s, 2H), 8.23 (s, 1H), 8.08 (s, 1H), 7.95 (d, J=0.76 Hz, 1H), 7.73 (s, 1H), 6.97 (q, J=4.55 Hz, 1H), 4.70 (d, J=4.55 Hz, 1H), 4.19 (tt, J=3.95, 11.59 Hz, 1H), 3.48-3.59 (m, 1H), 3.02 (d, J=4.80 Hz, 3H), 2.07 (d, J=12.13 Hz, 2H), 1.82-2.01 (m, 4H), 1.31-1.46 (m, 2H); MS (ESI): 446.16 [M+H]+; HPLC tR=2.50 min.

Provenance & Evidence