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 (1.00 g, B99), (2-fluorophenyl)boronic acid (337 mg), dichlorobis(tricyclohexylphosphine)palladium (137 mg) and aqueous cesium carbonate solution (1.4 ml, 2.0 M) are placed in a microwave tube and DME (15 ml) is added. The reaction vessel is sealed and the mixture is subjected to microwave irradiation at 150° C. with stirring for 40 min. The mixture is allowed to cool to RT, additional (2-fluorophenyl)boronic acid (52 mg) is added and the vessel is subjected to microwave irradiation at 150° C. for additional 40 min. The mixture is allowed to cool to RT and then filtered over a plug of silica (eluent: DCM). After removal of all volatile materials the residue is purified by flash column chromatography [silica gel, eluation gradient: cyclohexane/EtOAc, 1/0 to 2/3 (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 which is crystallized from toluene and directly used for step 2.

1. customThe reaction vessel is sealed
2. customirradiation at 150° C.
3. customirradiation at 150° C. for additional 40 min
4. temperatureto cool to RT
5. filtrationfiltered over a plug of silica (eluent: DCM)
6. customAfter removal of all volatile materials the residue
7. customis purified by flash column chromatography [silica gel, eluation gradient: cyclohexane/EtOAc, 1/0 to 2/3 (v/v)]