To an oven dried vial were added 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((S)-1-p-tolylethyl)morpholine-3-carboxamide (PREPARATION x32, 588 mg, 1.337 mmol), potassium phosphate tribasic (284 mg, 1.337 mmol), Xantphos (58.0 mg, 0.100 mmol) and palladium(II) acetate (15.01 mg, 0.067 mmol) in dioxane (15 mL) and tert-butanol (3 mL). The reaction mixture was degassed for 5 minutes with N2. The vial was then sealed and heated to 105° C. and the contents were stirred for 18 hours to give a brown suspension. The reaction mixture was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×5 mL and brine (3×5 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetatehexane gradient to give two diastereomers whose absolute configuration was not assigned (Diastereomer 1, higher Rf, 97 mg; Diastereomer 2, lower Rf, 91 mg; 39% overall). Diastereomer 1: 1H NMR (400 MHz, DMSO-d6) δ 1.69 (d, J=7.33 Hz, 3 H), 2.29 (s, 3 H), 2.89-3.04 (m, 1 H), 3.46-3.67 (m, 2 H), 3.89-4.01 (m, 1 H), 4.13-4.27 (m, 2 H), 4.50-4.63 (m, 1 H), 6.16-6.30 (m, 1 H), 7.13-7.29 (m, 4 H), 7.29-7.38 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H19ClN4O2, 359.12; found 359.3. Diastereomer 2: 1H NMR (400 MHz, DMSO-d6) δ 1.75 (d, J=7.07 Hz, 3 H), 2.28 (s, 3 H), 2.90-3.04 (m, 1 H), 3.51-3.62 (m, 1 H), 3.64-3.75 (m, 1 H), 3.89-3.98 (m, 1 H), 4.16-4.26 (m, 2 H), 4.43-4.51 (m, 1 H), 6.06-6.17 (m, 1 H), 7.18 (d, J=2.53 Hz, 4H), 7.47 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H19ClN4O, 359.12; found 359.3.
