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

温度

100 °C

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_

ORDレコード

ord-4c19150105e34defaeb92ce9b0748e42

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示