反应详情

温度

125 °C

A glass microwave reaction vessel was charged with 2-chloro-6-(4,4-difluoropiperidin-1-yl)pyrazine (300 mg, 1.28 mmol) and (Me3Sn)2 (0.32 mL, 1.54 mmol) in p-dioxane (2.5 mL) followed by Pd(PPh3)4 (60 mg, 0.05 mmol). The reaction was heated in a microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 125° C. for 30 min. The mixture was cooled to RT and 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (0.615 g, 1.024 mmol) was added followed by DMF (1 mL), CuI (244 mg, 1.28 mmol) and Pd(PPh3)4 (59 mg, 0.05 mmol). The reaction was heated in a microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 125° C. for 0.5 h. It was diluted with 5 mL of acetone and 10 mL of EtOAc, filtered through a pad of Celite. The filtrate was concentrated. The residue was loaded on a silica gel column and eluted with 50% EtOAc in DCM followed by 10-20% MeOH in EtOAc to give 5-(3-(6-(4,4-difluoropiperidin-1-yl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (590 mg) as a brown amorphous solid that was used in the next step without further purification. MS (ESI, pos. ion) m/z 672.0 (M+1).

1. customA glass microwave reaction vessel
2. temperatureThe mixture was cooled to RT
3. temperatureThe reaction was heated in a microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 125° C. for 0.5 h
4. filtrationfiltered through a pad of Celite
5. concentrationThe filtrate was concentrated
6. washeluted with 50% EtOAc in DCM