Reaction Steps
To a stirred solution of (S)-4-(8-cyclopropyl-9-ethyl-6-(3-methylmorpho-lino)-9H-purin-2-yl)aniline (52.0 mg, 0.14 mmol) in anhydrous 1,2-dichloroethane (3.0 mL) was added triethylamine (0.063 mL, 0.45 mmol, 3.3 eq.). The reaction was cooled to 0° C. and triphosgene (40.8 mg, 0.14 mmol, 1.0 eq) was added in one portion. After stirring at 0° C. under N2 for 5 minutes, the reaction mixture was stirred at 70° C. for 1 h. The reaction mixture was cooled to RT, and 3-oxetanamine (50.2 mg, 0.69 mmol, 5.0 eq.) was then added. The reaction mixture was stirred at RT under N2 for 16 h and then diluted with ethyl acetate (25 mL). The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified by reverse phase HPLC to give the title compound as a white solid (30.5 mg, 46.5%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.78 (s, 1H), 8.24 (d, J=8.7 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 6.97 (d, J=6.7 Hz, 1H), 5.37 (broad s, 1H), 5.03 (broad s, 1H), 4.86 to 4.69 (m, 3H), 4.44 (t, J=6.0 Hz, 2H), 4.35 (q, J=7.1 Hz, 2H), 3.97 (d, J=8.7 Hz, 1H), 3.77 (d, J=11.3 Hz, 1H), 3.68 (dd, J=11.4 Hz, 2.6 Hz, 1H), 3.53 (t, J=10.5 Hz, 1H), 3.44 to 3.33 (m, 1H), 2.30 to 2.19 (m, 1H), 1.39 (t, J=7.2 Hz, 3H), 1.28 (d, J=6.7 Hz, 3H), 1.10 to 0.95 (m, 4H); LC-MS m/z (method C)=478.2 [M+H]+, RT=4.44 min.
