Cesium fluoride → [4-[6-Amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-2-(4-piperidyl)pyrazol-3-yl]methanol

Participants

Reaction Conditions

Reaction Steps

Tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (250 mg), tert-butyl 4-(4-bromo-5-(hydroxymethyl)pyrazol-1-yl)piperidine-1-carboxylate (131 mg), bis(triphenylphosphine) palladium chloride (12.73 mg) and caesium fluoride (165 mg) were weighed out in a microwave vial and sealed. Methanol (3 ml) was added and argon was let to bubble in the resulting suspension for 5 minutes. The resulting mixture was heated in the microwave at 120° C. for 20 minutes. Insolubles were removed by filtration and the filtrate was concentrated. Hydrogen chloride (5N in isopropanol) (1.814 ml) was added and the mixture was heated at reflux for 2 hours. The resulting precipitate was collected by filtration, washed with isopropanol. The solid was taken up into methanolic ammonia (7N-2 mL) and dicalite speed plus. The crude product was purified by flash chromatography on silica gel eluting with 5 to 10% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford [4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-2-(4-piperidyl)pyrazol-3-yl]methanol (60 mg). NMR Spectrum: (DMSOd6) 1.80-1.89 (m, 2H), 1.93 (dd, 1H), 1.98 (dd, 1H), 2.25 (bs, 1H), 2.57-2.67 (m, 2H), 3.03-3.11 (m, 2H), 4.37-4.46 (m, 1H), 4.56 (d, 2H), 5.46 (t, 1H), 7.41-7.48 (m, 2H), 7.70 (bs, 2H), 7.71 (s, 1H), 7.79 (dd, 1H), 7.85 (dd, 1H), 8.35 (d, 1H), 8.36 (d, 1H). Mass spectrum: M+H+ 391;

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