反应详情

温度

130 °C

A mixture of 6′-bromo-5-methyl-5″,6″-dihydro-4″H-dispiro[imidazole-2,4′-chromene-2′,3″-pyran]-4-amine (Example 45 Isomer 1, 116 mg, 0.32 mmol), 3-chlorophenylboronic acid (64.7 mg, 0.41 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (26.0 mg, 0.03 mmol), K2CO3 (2 M aq) (0.318 mL, 0.64 mmol) and 1,4-dioxane (2 mL) were added to a microwave vial. The vial was capped, evacuated and filled with argon. The vial was heated in a microwave reactor at 130° C. for 20 min. Brine was added and the residue was extracted with DCM (×3), dried with a phase separator and concentrated under reduced pressure. The crude product was purified by preparative chromatography. The desired fractions were concentrated. Water and DCM were added and the layers separated. The organic phase was dried with a phase separator and concentrated to give isomer 1 of the title compound (38.5 mg, 30% yield) with undetermined configuration: 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.44-1.53 (m, 1 H), 1.83-1.92 (m, 3 H), 2.01 (d, 2 H), 2.22 (s, 3 H), 3.41-3.48 (m, 1 H), 3.56 (d, 1 H), 3.67-3.73 (m, 1 H), 3.99 (d, 1 H), 6.58 (s, 1 H), 6.62 (s, 1 H), 6.95 (d, 1 H), 7.31-7.39 (m, 2 H), 7.39-7.47 (m, 3 H); MS (ES+) m/z 396 [M+H]+.

1. additionwere added to a microwave vial
2. customThe vial was capped
3. customevacuated
4. additionfilled with argon
5. additionBrine was added
6. extractionthe residue was extracted with DCM (×3)
7. customdried with a phase separator
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified by preparative chromatography
10. concentrationThe desired fractions were concentrated
11. additionWater and DCM were added
12. customthe layers separated
13. customThe organic phase was dried with a phase separator
14. concentrationconcentrated