反应详情

Tert-butyl 4-{6-bromo-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate (250 mg, compound B99), (2-fluorophenyl)boronic acid (65 mg), dichlorobis(tricyclohexylphosphine)palladium (17 mg) and aqueous cesium carbonate solution (0.35 ml, 2.0 M) are placed in a microwave tube and DME (8 ml) is added. The reaction vessel is sealed and the mixture is subjected to microwave irradiation at 150° C. with stirring for 20 min. The mixture is allowed to cool to RT and additional (2-fluorophenyl)boronic acid (19 mg) and dichlorobis(tricyclohexylphosphine)palladium (9 mg) are added. The mixture is again subjected to microwave irradiation at 150° C. with stirring for 20 min and then allowed to cool to RT. After addition of water and extraction with EtOAc the combined organic layers are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. All volatile materials are removed in vacuo and the residue is purified by flash column chromatography [silica gel, eluent: cyclohexane/EtOAc, 3/1 (v/v)] to afford tert-butyl 4-{1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-6-(2-fluorophenyl)-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate as a solid.

1. customThe reaction vessel is sealed
2. customirradiation at 150° C.
3. customirradiation at 150° C.
4. stirringwith stirring for 20 min
5. temperatureto cool to RT
6. washare washed with saturated aqueous sodium chloride solution
7. dry with materialdried over sodium sulfate
8. customAll volatile materials are removed in vacuo
9. customthe residue is purified by flash column chromatography [silica gel, eluent: cyclohexane/EtOAc, 3/1 (v/v)]