Reaction Steps
To a solution of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-furo[3,2-c]pyridin-6-ylamine (32.6 mg, 0.0776 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole (18.0 mg, 0.0854 mmol) in 1,4-dioxane (1.1 mL, 14 mmol) in a microwave reactor tube were added PS-PPh3-Pd (0.10 mmol/g loading; 45 mg, 0.0045 mmol; Argonaut) and a solution of Cs2CO3 (52.1 mg, 0.160 mmol) in H2O (0.33 mL, 18 mmol). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 105° C. for 30 min. Further 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole (21 mg, 0.099 mmol) was added, and the reaction mixture was heated in the microwave reactor to 105° C. for 30 min. A solution of the remaining 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole (61 mg, 0.29 mmol) in 1,4-dioxane (0.30 mL, 3.8 mmol) was added to the reaction mixture, which was then heated to 105° C. for 45 min. The resin was filtered off and washed with DCM. The combined filtrate and washings were diluted with DCM to 50 mL, washed with water and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was submitted to MDP for purification. The product fractions were combined and dried in vacuo overnight. The product was chromatographed on an SCX column (500 mg/3 mL), and the fraction eluting with NH3/MeOH was concentrated and dried in vacuo to give the title compound as an off-white film. 1H NMR (CDCl3, 400 MHz): δ=8.91 (d, J=2.4 Hz, 1H), 8.43 (s, 1H), 7.98 (s, 1H), 7.53 (d, J=2.4 Hz, 1H), 7.29 (dd, J=4.8, 8.0 Hz, 1H), 7.06 (dd, J=8.0, 8.8 Hz, 1H), 6.62 (q, J=6.8 Hz, 1H), 5.29 (brs, 2H), 1.91 (d, J=6.8 Hz, 3H). MS (ES+): m/z=423.90/425.88/427.86 (98/100/28) [MH+], 234.00 (25) [MH+−3-F-2,6-di-Cl-Ph-CH═CH2]. HPLC: tR=3.33 min (polar—5 min, ZQ3).
