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

関与物質

反応条件

反応手順

To a stirred solution of 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (28 g, 89.70 mmol) in 1,4-dioxane (300 mL) were added 1-isopropyl-3-methyl-1H-pyrazol-5-amine (14.98 g, 107.64 mmol), cesium carbonate (43.8 g, 134.55 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.67 g, 8.07 mmol) and diacetoxypalladium (1.208 g, 5.38 mmol) Mixture was degassed 3 times with N2 and heated to reflux overnight: OK. Reaction was cooled down, then filtered, salts were washed with 500mL of a 90/10 solution of CH2Cl2/MeOH and the filtrate was concentrated. Residue was then dissolved in CH2Cl2/MeOH, adsorbed on silica and purified by chromatography, eluting with 7% of MeOH in CH2Cl2. Solvent were concentrated and the solid obtained was stirred in 300mL of AcOEt for 3h. product was filtered, washed with AcOEt and dried on vacuum at 50°C for the we. 1H NMR indicates the presence of 7% of AcOEt... Need to dissolve the product in EtOH, then concentrated to dryness and stirred with 500mL of water for 3h. Solid was filtered, washed with water and dried on vacuum overnight at 50°C to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (21.50 g, 57.8 %) as a white powder. Purity-check OK.

情報源と証拠