Cesium carbonate → 5-Phenyl-3-(2,2,2-trifluoroethyl)furo[2,3-d]pyrimidin-4(3H)-one
Reaction equation
[C:1]1([C:7]2[C:15]3[C:14](=[O:16])[NH:13][CH:12]=[N:11][C:10]=3[O:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:23][C:24]([F:28])([F:27])[CH2:25]I>CN(C=O)C.O>[C:1]1([C:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:25][C:24]([F:28])([F:27])[F:23])[CH:12]=[N:11][C:10]=3[O:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 70 °C
Procedure
To a solution of 5-phenylfuro[2,3-d]pyrimidin-4(3H)-one (2 g, 9.42 mmol, prepared as described in WO2006/004658) in DMF (20 ml) was charged cesium carbonate (6.76 g, 20.7 mmol) and 1,1,1-trifluoro-2-iodoethane (1.86 ml, 18.9 mmol). The reaction was heated at 70° C. for 18 h under a nitrogen atmosphere. A further 1 eq. of 1,1,1-trifluoro-2-iodoethane was charged to the reaction mixture. The reaction was heated to 100° C. for 5 h before being cooled to RT, diluted with water and extracted twice with ethyl acetate. The organic extracts were washed with brine (3×50 ml), dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was purified by silica gel chromatography (SiO2, 0 to 50% EtOAc in cyclohexane) affording the title compound as a beige solid (730 mg, 26%). LCMS RT=1.27 min, M+H+=295.
Workup
- temperatureThe reaction was heated to 100° C. for 5 h
- temperaturebefore being cooled to RT
- extractionextracted twice with ethyl acetate
- washThe organic extracts were washed with brine (3×50 ml)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe resultant residue was purified by silica gel chromatography (SiO2, 0 to 50% EtOAc in cyclohexane)
Sources & evidence
- ORD record
- ord-649a2766c3da49bdb2e8e1f64e58d77c
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156853B2
Reaction notes
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