Cesium carbonate → N-(5-chloro-2-nitrophenyl)-8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

関与物質

反応条件

反応手順

To an oven-dried vial was added 8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine (56 mg, 0.18 mmol, 1 equiv.) in anhydrous toluene (1 mL), then freshly grounded cesium carbonate (82 mg, 0.25 mmol, 1.4 equiv.) with stirring at room temperature under Ar. After 10 min, Pd(OAc)2 (13.5 mg, 0.02 mmol, 0.1 equiv.), racemic BINAP (17 mg, 0.03 mmol, 0.15 equiv.) and 1-bromo-5-chloro-2-nitrobenzene (WO 02/053545 A1) (55 mg, 0.23 mmol, 1.3 equiv.) were added as solids. The vial was purged with Ar for 3 min, then closed and heated in a microwave oven at 170° C. for 2 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate/methylene chloride, filtered through a Nylon 0.45 μm filter, and the filtrate was concentrated in vacuo. The resulting residue was purified using preparative TLC (silica gel, 7.5% methanol in methylene chloride) to give the desired product as a yellow solid (18 mg, 21% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.30 (s, 1H), 8.77 (br m, 2H), 8.64 (br m, 2H), 8.26 (d, J=8.9 Hz, H), 7.05 (d, J=7.9 Hz, 1H), 4.60-4.56 (m, 1H), 4.26-4.22 (m, 2H), 3.64 (app t, J=11.9 Hz, 2H), 2.94-2.90 (m, 2H), 2.76 (s, 3H), 1.91 (br d, J=11.2 Hz, 2H); MS (EI) m/z 466.3 (MH)+.

情報源と証拠