反应详情

温度

90 °C

A solution of 1-{4-chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3′,5′-difluorobiphenyl-2-yl}ethanamine (60 mg, 0.15 mmol), 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (63 mg, 0.22 mmol, from Example 108, Step 1), and N,N-diisopropylethylamine (77 μL, 0.44 mmol) in ethanol (2.8 mL) was heated in the microwave at 130° C. for 30 minutes. Alternatively, this reaction can be heated at 90° C. overnight on the benchtop. The reaction mixture was cooled to room temperature, treated with 6 M Hydrogen chloride in water (0.49 mL, 3.0 mmol), and stirred for 30 minutes. The reaction mixture was diluted slightly with methanol, filtered, and directly purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (29 mg, 43%). LCMS for C22H17ClF2N7 (M+H)+: m/z=452.1. Found: 452.0; 1H NMR (300 MHz, DMSO-d6): δ 12.8 (br s, 1H), 8.32-8.23 (m, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.36-7.23 (m, 3H), 7.09-7.01 (m, 1H), 6.96 (d, J=8.5 Hz, 1H), 5.09-4.96 (m, 1H), 1.34 (d, J=6.7 Hz, 3H).

1. customAlternatively, this reaction
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfiltered
4. customdirectly purified via preparative LCMS (XBridge C18 column
5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)