1-Isopropyl-3-methyl-1H-pyrazol-5-amine → Gsk-2256098

関与物質

反応条件

反応手順

2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (5 g, 16.02 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (2.453 g, 17.62 mmol) and cesium carbonate (7.83 g, 24.03 mmol) were suspended in 1,4-dioxane (75 mL). Nitrogen was bubbled through mixture for 15 minutes. (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.834 g, 1.44 mmol) and diacetoxypalladium (0.216 g, 0.96 mmol) were added and flask was purged with nitrogen (x3). Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 60 mL). Silica (63-200 µm) was added to the filtrate and mixture was concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 6% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (3.35 g, 50.4 %) as a dark green foam => _contains CH2Cl2 and MeOH._ EtOAc (10 mL) was added and mixture was stirred at room temperature for 5 hours. The resulting solid was filtered, washed with cold EtOAc and dried under high vacuum at 50°C overnight to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (2.41 g, 36.3 %) as a pale yellow solid => _crystalline powder under polarized light microscopy_

情報源と証拠