Reaction Steps
To a racemic solution of 2-chloro-5-fluoro-6-(1-hydroxy-4,4-dimethylpentan-3-ylamino)pyridine-3-carbonitrile, 95a, (0.20 g, 0.70 mmol) and 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 7a, (0.44 g, 1.05 mmol) in THF (15 mL) was added a solution of potassium phosphate (0.45 g) in 3 mL of water. The resulting mixture was degassed under a stream of nitrogen for 15 minutes. To the mixture was then added X-Phos (0.03 g, 0.07 mmol) and Pd2(dba)3 (0.02 g, 0.04 mmol). The reaction was warmed to 135° C. via microwave irradiation for 15 minutes and then extracted into EtOAc (3×15 mL) vs. water. The organic layers were combined and concentrated in vacuo to a dark oil which was redissolved in 20 ml, of THF. To the solution was added 5 mL of 2 N LiOH and the reaction was warmed to 65° C. for 12 hrs and then concentrated in vacuo. The resulting residue was purified via silica gel chromatography (EtOAc) to afford 108 mg of the desired product, 41, as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 12.40 (s, H), 8.63 (dd, J=2.8, 10.1 Hz, H), 8.37-8.32 (m, H), 7.83 (d, J=11.4 Hz, H), 7.31 (d, J=9.7 Hz, H), 4.56-4.50 (m, H), 4.41 (dd, J=4.1, 5.2 Hz, H), 3.69 (s, H), 3.57 (s, H), 3.49 (t, J=6.6 Hz, H), 3.48 (s, H), 3.36-3.28 (m, H), 2.50 (qn, J=1.8 Hz, H), 1.86-1.67 (m, 2 H), 1.21 (dd, J=7.0, 16.1 Hz, H) and 0.94 (s, 9 H) ppm; LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=3.09 minutes (M+H) 386.39.
