Reaction Steps
A mixture of 5-bromo-4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-2-methylpyrimidine (2-3) (120 mg, 0.3 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (OO2) (104 mg, 0.4 mmol), tripotassium phosphate (145 mg, 0.7 mmol), S-Phos (14 mg, 0.03 mmol), and Pd(OAc)2 (3.9 mg, 0.02 mmol) in THF (1.5 mL) and water (0.3 mL) was heated at 100° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (10 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a colorless gum. 1H NMR (500 MHz, DMSO): δ 8.51 (s, 1 H), 8.14 (d, J=2.9 Hz, 1 H), 7.84 (s, 1 H), 7.31-7.22 (m, 2 H), 4.53 (dd, J=11.3, 6.4 Hz, 1 H), 4.25 (dd, J=11.3, 8.2 Hz, 1 H), 4.04 (t, J=7.3 Hz, 2 H), 3.78 (s, 3 H), 2.97 (t, J=7.3 Hz, 2 H), 2.50 (s, 3 H), 2.39-2.32 (m, 2 H), 2.19 (dd, J=8.4, 4.7 Hz, 1 H), 1.79 (m, 1 H), 1.17 (dt, J=8.6, 4.5 Hz, 1 H), 1.06 (dd, J=8.6, 4.9 Hz, 1 H); HRMS m/z (M+H) 378.1921 found, 378.1925 required.
