反应详情

6-Bromo-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde (Example 26d 16.8 g), N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (20.61 g), Pd-118 (1.619 g) and potassium carbonate (17.16 g) in DMF (140 mL) was heated to 70° C. for 4 h under nitrogen. The mixture was cooled, diluted with water (250 mL), and extracted with ethyl acetate (300 mL). The separated organic layer was dried (MgSO4), filtered and evaporated. The residue was purified (SiO2 chromatography, elution with 50 to 100% ethyl acetate in DCM) to give a solid, which was triturated with isohexane 1:1 diethyl ether (200 mL) for 1 h. The suspension was filtered and dried to give the subtitle compound (14.5 g) as a solid.

1. customwas heated to 70° C. for 4 h under nitrogen
2. temperatureThe mixture was cooled
3. extractionextracted with ethyl acetate (300 mL)
4. dry with materialThe separated organic layer was dried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified
8. wash(SiO2 chromatography, elution with 50 to 100% ethyl acetate in DCM)
9. customto give a solid, which
10. customwas triturated with isohexane 1:1 diethyl ether (200 mL) for 1 h
11. filtrationThe suspension was filtered
12. customdried