Morpholine → 2-Chloro-4-morpholin-4-yl-7-trifluoromethyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine
Reaktionsgleichung
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([OH:9])=[C:4](Cl)[N:3]=1.[F:11][C:12]([F:17])([F:16])[CH:13]1[CH2:15][O:14]1.C(N(CC)CC)C.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>>[Cl:1][C:2]1[N:7]=[C:6]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:5]2[O:9][CH2:15][CH:13]([C:12]([F:17])([F:16])[F:11])[O:14][C:4]=2[N:3]=1Komponenten
Reaktionsbedingungen
- Temperatur
- 95 °C
Versuchsvorschrift
A microwave vial was charged with 2,4,6-trichloro-pyrimidin-5-ol (200 mg, 1.00 mmol) and 2-trifluoromethyl-oxirane (429 μL, 5.01 mmol) then sealed. The reaction mixture was heated at 95° C. for 48 hours before being cooled and concentrated in vacuo. The resultant residue was dissolved into IMS (5 mL) then treated with triethylamine (198 μL, 1.42 mmol) and morpholine (83 μL, 0.95 mmol). The orange mixture was stirred for 18 hours at RT before being concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-20% ethyl acetate in cyclohexane) affording 2-Chloro-4-morpholin-4-yl-7-trifluoromethyl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (105 mg, 32%). LCMS: RT=3.20 min, [M+H]+=326/328.
Aufarbeitung
- customthen sealed
- temperaturebefore being cooled
- concentrationconcentrated in vacuo
- dissolutionThe resultant residue was dissolved into IMS (5 mL)
- concentrationbefore being concentrated in vacuo
- customThe resulting residue was purified by column chromatography (SiO2, gradient 0-20% ethyl acetate in cyclohexane)
Quellen und Nachweise
- ORD-Eintrag
- ord-f995dfa0127946bd83177e1bd40c7811
- Quelldatensatz
- uspto-grants-2016_05
- Patentnummer
- US09346817B2
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