反应详情

温度

120 °C

6-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (35 mg, 0.15 mmol, from Example 176, Step 4) and DIPEA (0.04 mL, 0.2 mmol) were added to 4-(1-aminoethyl)-3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrile in ethanol (2 mL). The reaction was heated to 120° C. overnight. The reaction was allowed to cool to room temperature and was concentrated in vacuo to give 3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)benzonitrile as a solid residue. This intermediate was dissolved in 4.0 M HCl in dioxane (1 mL) and was stirred for 10 minutes. The reaction was concentrated and was purified on prep HPLC on a C-18 column eluting with water:acetonitrile gradient buffered with TFA to give 3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-[1-(9H-purin-6-ylamino)ethyl]benzonitrile as a white solid (0.010 g, 16%). LCMS calculated for C23H24N7O3S (M+H)+: m/z=478.1. found: 478.1. 1H NMR (300 MHz, DMSO-d6) δ 9.18 (d, J=2.2 Hz, 1H), 9.09 (d, J=2.0 Hz, 1H), 8.75 (m, 1H), 8.54 (t, J=2.1 Hz, 1H), 8.33 (m, 2H), 7.68 (s, 1H), 5.80 (m, 1H), 3.99-3.79 (m, 1H), 3.40 (s, 3H), 3.34 (m, 1H), 2.47 (s, 3H), 1.58 (d, J=6.9 Hz, 3H), 0.98 (t, J=6.9 Hz, 3H).

1. temperatureto cool to room temperature
2. concentrationwas concentrated in vacuo