反应详情

温度

130 °C

A 20 mL microwave vial was charged with 5-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (185 mg, 0.342 mmol), Xphos (Strem Chemicals, Newburyport, Mass., 9.8 mg, 0.021 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 9.4 mg, 10.27 μmol), 2-bromo-4-cyclopropylpyrimidine (CombiPhos Catalysts Inc., Princeton, N.J., 82 mg, 0.411 mmol) and potassium phosphate (218 mg, 1.03 mmol) followed by purging with argon. The solids were treated with dioxane (4.0 mL) and water (1.0 mL) and heated in the microwave at 130° C. for 20 min. The reaction mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded 5-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (186.7 mg, 0.351 mmol, 102% yield) as a viscous yellow oil in ca. 90% purity. MS (ESI, pos. ion) m/z: 533.0 (M+H)+. The material was used in the subsequent step without further purification.

1. customby purging with argon
2. additionThe solids were treated with dioxane (4.0 mL) and water (1.0 mL)
3. additionThe reaction mixture was treated with water
4. extractionextracted with EtOAc
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column