Methanol → HCID 178508373, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (232 mg, 0.520 mmol), 5-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thieno[2,3-c]pyridine (235 mg, 0.530 mmol), and Pd(PPh3)4 (60.1 mg, 0.0520 mmol) in 1,4-dioxane (2.0 mL) and aqueous 1.0 M sodium carbonate solution (2.0 mL, 2.0 mmol) was heated to 120° C. in a microwave reactor for 60 min. Water (10 mL) was added, and the mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water (2×10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated. The residue was transferred to a sealable vial. To the vial was added sodium methoxide (148 mg, 2.60 mmol) and methanol (5.0 mL, 120 mmol), and the reaction mixture was heated in a microwave at 150° C. for 2 h. Water (10 mL) was added, and the mixture was extracted with EtOAc (3×15 mL). The organic extracts were washed with water (2×10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated. The residue was transferred to a vial, to which was added pyridine hydrochloride (613 mg, 5.20 mmol) and water (10.0 mL), and the mixture was heated at 120° C. for 3 h followed by heating in a microwave at 150° C. for 2 h. Purification of the residue by MDPS afforded 25.6 mg (11%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.70 (s, 1H), 8.66 (s, 1H), 8.25 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.58 (s, 1H), 7.56 (s, 1H), 6.36 (brs, 2H), 4.70 (br s, 1H), 4.19 (tt, J=11.4, 4.0 Hz, 1H), 3.59-3.45 (m, 1H), 2.12-2.04 (m, 2H), 2.02-1.82 (m, 4H), 1.45-1.33 (m, 2H), 1H overlapping with water peak; MS (ESI): 448.31 [M+H]+; HPLC: tR=2.37 min (ZQ3: polar—5 min).

Provenance & Evidence