Reaktion #388
ord-a11b668f474546c6bffcfc85e307c94b
Reaktionsgleichung
Lösungsmittel
Reaktionsbedingungen
Vorschrift
2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide (8.9 g, 25.60 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (3.41 g, 30.72 mmol), diacetoxypalladium (0.460 g, 2.05 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.370 g, 4.10 mmol) and cesium carbonate (10.01 g, 30.72 mmol) were suspended in 1,4-dioxane (111 ml). The reaction was degased, purged with nitrogen and heated to 90°C (internal temperature) for 4 hours _._ Reaction was concentrated to dryness. Residue was diluted with CH2Cl2/MeOH 9/1 (200 mL) and water (200 mL). Aqueous was extracted with CH2Cl2/MeOH 9/1 (100 mL). Combined organic layers were dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (7.6 g) as a yellow foam => _1H NMR showed that it contained EtOAc and a vey small amount of an impurity_. This residue was triturated in CH2Cl2 (10 mL) => _complete solubilisation followed by precipitation._ The resulting solid was filtered and washed with tBuOMe (10 mL) to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (6.3 g) as a pale yellow solid => _1H NMR showed that EtOAc and impurity has been removed_ This solid was suspended in tBuOMe (20 mL) and stirred at 50°C (heating block temperature) for 1 hour. Mixture was allowed to cool for 5 minutes then filtered, washed once with tBuOMe (10 mL) and dried overnight under high vacuum at 50°C to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (6.00 g, 55.5 %) as a white solid.