1,2-Dichloroethane → 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide

Participants

Reaction Steps

4-(5-Bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (PREPARATION x30, 1 g, 3.10 mmol), EDC (0.892 g, 4.65 mmol), HOBt (0.712 g, 4.65 mmol), (R)-1-(4-chlorophenyl)ethanamine (0.724 g, 4.65 mmol) and triethylamine (1.296 mL, 9.30 mmol) were dissolved in DMF (15 mL). The resulting brown solution was stirred at room temperature for 18 hours and was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow foam (574 mg, 40%). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (dd, J=7.07, 4.29 Hz, 3H), 3.55 (d, J=6.32 Hz, 2H), 3.68-3.79 (m, 1H), 3.84-3.91 (m, 1H), 4.22-4.39 (m, 2H), 4.86 (m, 1H), 4.89-5.03 (m, 1H), 7.31-7.41 (m, 4H), 8.45 (d, J=10.61 Hz, 2H).

Provenance & Evidence