Cesium fluoride → N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Steps

To a solution of N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (46.3 mg, 88.2 μmol) in acetonitrile (5 mL) was added CsF (134 mg, 882 μmol) and 18-crown-6 (70.0 mg, 265 μmol), the reaction mixture was heated to reflux with stirring for 48 h, reaction diluted with dichloromethane (20 mL), filtered over celite and concentrated. The residue was dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. The pure product dissolved in dichloromethane/MeOH and cyclohexane added to allow solid formation, which was separated by decantation and dried to give N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (18 mg, 45.6 μmol, 51.7%) as a yellow solid. MS (M+H)+=377; 1H NMR (DMSO-d6) δ: 8.96 (s, 1H), 8.34 (s, 1H), 7.98 (br. s., 1H), 7.79 (br. s., 1H), 7.68 (d, J=9.1 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 4.93 (br. s., 1H), 4.13 (s, 3H), 3.86 (s, 3H), 3.60 (d, J=4.9 Hz, 2H), 1.39 (s, 6H).

Provenance & Evidence