反应详情

温度

125 °C

To a 10 mL microwave vial, 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxamide (100 mg, 400 μmol, Eq: 1.00), 2-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one (137 mg, 400 μmol, Eq: 1.00), X-phos (19.1 mg, 40.0 μmol, Eq: 0.1), Pd2(dba)3 (18.3 mg, 20.0 μmol, Eq: 0.05), and potassium phosphate tribasic (212 mg, 1.00 mmol, Eq: 2.50) were added, followed by 1,4-dioxane (5 ml) and water (0.5 ml) to give a dark brown suspension. The reaction mixture was stirred while purging with argon for 10 min. The solution was heated at 125° C. in a microwave for 30 min. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with 50 mL of dichloromethane and extracted with water. The aqueous was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 25%-50% [60:10:1 dichloromethane:methanol:aqueous ammonium hydroxide]/dichloromethane gradient) to give 4-[3-(6-cyclopropyl-8-fluoro-1-oxo-1H-isoquinolin-2-yl)-2-hydroxylmethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (25.9 mg, 15%) as a white solid: LC/MS-ESI observed [M+H]+ 432.

1. customto give a dark brown suspension
2. customwhile purging with argon for 10 min
3. temperatureThe reaction mixture was cooled to room temperature
4. additionThe reaction mixture was diluted with 50 mL of dichloromethane
5. extractionextracted with water
6. concentrationThe aqueous was concentrated in vacuo
7. customThe crude material was purified by flash chromatography (silica gel, 25%-50% [60:10:1 dichloromethane:methanol:aqueous ammonium hydroxide]/dichloromethane gradient)