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

HRID 1043811Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([Cl:13])[CH:10]=[C:9](Cl)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.CCOC(C)=O>CN1C(=O)CCC1>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[N:8]=[C:9]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:10]=[C:11]([Cl:13])[N:12]=2)[CH2:5][CH2:6]1

Participants

Conditions

Temperature: 85 °C

Procedure

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).

Workup

temperaturethe solution was cooled
washThe organic solution was washed with 25 mL of NaHCO3(sat.) (2×), water (2×) and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
dissolutionThe crude material was dissolved in 200 mL EtOAc
filtrationfiltered through a SiO2 pad
washfurther eluting with EtOAc

Sources & evidence

ORD record: ord-11aa03d3bb7343979e9f69361b418cba
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563549B2

Reaction notes

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