反应详情

温度

90 °C

Saturated aqueous sodium carbonate (0.2 mL) was added to a mixture of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (100 mg, 0.20 mmol), 4-bromo-3-chloroaniline (46 mg, 0.22 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol), and water (0.3 mL). The reaction mixture was purged with nitrogen and then 1,4-dioxane (0.7 mL) was added. The reaction mixture was degassed, stirred, and heated at 90° C. overnight. Water and ethyl acetate were added; the reaction mixture was concentrated; dissolved in 1:1 acetic acid:water (1 mL) and purified by preparative HPLC. Fractions were combined, adjusted to pH 8-9 with aqueous sodium bicarbonate, and extracted with DCM. Extracts were washed with water, dried with sodium sulfate, and concentrated. The concentrate was dissolved in methanol and concentrated under vacuum to provide the title compound (m/z): [M+H]+ calcd for C26H30ClN5O3 496.20 found 496.7.

1. customThe reaction mixture was purged with nitrogen
2. addition1,4-dioxane (0.7 mL) was added
3. customThe reaction mixture was degassed
4. additionWater and ethyl acetate were added
5. concentrationthe reaction mixture was concentrated
6. dissolutiondissolved in 1:1 acetic acid
7. customwater (1 mL) and purified by preparative HPLC
8. extractionextracted with DCM
9. washExtracts were washed with water
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated
12. dissolutionThe concentrate was dissolved in methanol
13. concentrationconcentrated under vacuum