Morpholine → 4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

Participants

Reaction Conditions

Reaction Steps

To a slurry of 2-morpholino-4,6-dichloropyrimidine (prepared as in Method 22, 2.0 g, 8.54 mmol) in NMP (14 mL), triethylamine (1.43 mL, 10.25 mmol) was added. The heterogeneous mixture was stirred for 15 minutes, then treated with morpholine (0.75 mL, 8.54 mmol). Upon refluxing at 85° C. under argon for 2 hours, the solution was cooled, then added to EtOAc (160 mL). The organic solution was washed with 25 mL of NaHCO3(sat.) (2×), water (2×) and brine, dried over Na2SO4, filtered and concentrated. The crude material was dissolved in 200 mL EtOAc and filtered through a SiO2 pad, further eluting with EtOAc, yielding 2.2 g (93%) of 2,4-dimorpholino-6-chloropyrimidine as an off-white solid. LCMS (m/z): 285.0 (MH+), 1H NMR (CDCl3): δ 5.86 (s, 1H), 3.71-3.76 (m, 12H), 3.52-3.56 (m, 4H).

Provenance & Evidence