반응 #223
ord-80d00cb26739441d887e2e759be183c4
용매
반응 조건
실험 절차
8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), cesium carbonate (121 mg, 0.37 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.7 mg, 0.05 mmol) and diacetoxypalladium (5.57 mg, 0.02 mmol) were suspended in dioxane (2 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 12 hours. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (83 mg, 69.8 %) as a grey solid. Sample was combined with EN01622-31,32,33,35,36,37,38,39&40\. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (218 mg, EN01622-42-02) as a pale pink foam.