Nitrogen → 4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)-6-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 6-bromo-4-(((3S,4S)-1-(5-cyanopyridin-2-yl)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (20 mg, 0.045 mmol, from Step 2), 2-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol (24.18 mg, 0.091 mmol, from Step 3), potassium phosphate tribasic (28.9 mg, 0.136 mmol), palladium(II) acetate (1 mg, 4.45 μmol) and dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (4.78 mg, 8.90 μmol) in tert-butanol (0.5 mL) was degassed by vacuum-N2 refill cycle twice. The sealed tube was then heated at 110° C. for 2 h. The crude material was diluted with methanol (1.3 mL) and water (0.2 mL) and filtered. The filtrate was purified by preparative RP-HPLC (50-80% solvent B in 30 min, 30 mL/min, Pursuit XRs 10 u C18 30×250 mm) to give the title compound (9.7 mg). 1H NMR (500 MHz, 1:1 mixture of chloroform-d/methanol-d4) δ ppm 8.31 (br. s., 1H), 8.07 (s, 1H), 7.85 (s, 1H), 7.74 (s, 2H), 7.63 (dd, J=8.9, 1.5 Hz, 1H), 6.98 (d, J=1.5 Hz, 1H), 6.49 (d, J=8.9 Hz, 1H), 4.97 (br. s., 1H), 4.10 (s, 2H), 3.99-3.75 (m, 3H), 3.46-3.36 (m, 1H), 2.84 (br. s., 1H), 1.29 (d, J=6.9 Hz, 3H), 1.20 (s, 6H); MS (ES+) m/z: 500.2 (M+H); LC retention time: 1.18 min (analytical LCMS Method I).

Provenance & Evidence