8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one → 6-[(1,3-Dimethylpyrazol-4-yl)amino]-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridine-3-carbonitrile

関与物質

反応条件

反応手順

8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (35.6 mg, 0.20 mmol), 4-chloro-6-(1,3-dimethyl-1H-pyrazol-4-ylamino)nicotinonitrile (25 mg, 0.10 mmol), diacetoxypalladium (1.133 mg, 5.05 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.84 mg, 10.09 µmol) and cesium carbonate (39.5 mg, 0.12 mmol) were dissolved in dioxane (0.5 mL) and sealed into a microwave tube. nitrogen was let to bubble into the mixture then the reaction was heated to 100 °C for 90 minutes. Crude LCMS showed the expected product P3 and no hydrolysis by-product at all like in _EN01775-20_ !! The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. **10 days later** , the fractions containing the desired compound were evaporated to dryness to afford impure 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (13.00 mg, 33.2 %): it has probably gone off after 10 days in solution (aqueous ammonium carbonate and acetonitrile) ENCOURAGING, THOUGH.

情報源と証拠