反应详情

温度

130 °C

A mixture of 6′-bromo-5-methyl-2″,3″,5″,6″-tetrahydro-3′H-dispiro[imidazole-2,1′-indene-2′,4″-pyran]-4-amine (Example 25, 75 mg, 0.22 mmol), 3-chlorophenylboronic acid (40.4 mg, 0.26 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.86 mg, 10.77 μmol), 2 M aq. K2CO3 (0.215 mL, 0.43 mmol) and 1,4-dioxane (2 mL) were mixed in a vial and heated in a microwave reactor at 130° C. for 15 min. When cooled to r.t., the mixture was diluted with brine (3 mL) and extracted with DCM (3×3 mL). The combined organics were concentrated and the resulting residue was purified by preparative chromatography. The fractions containing the title compound were pooled, the solvent removed in vacuo, and the resulting aqueous residue was extracted with DCM (3×3 mL). The combined organics were passed through a phase separator and concentrated. The resulting residue was taken up in MeOH (2 mL) and dried in a vacuum oven at 40° C. over a weekend to give 36 mg (44% yield) of the title compound; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.55 (t, 1H), 7.49 (m, 2H), 7.39 (m, 3H), 6.80 (d, 1H), 6.61 (br. s, 1H), 3.66 (m, 2H), 3.48 (m, 1H), 3.40 (td, 1H), 3.22 (d, 1H), 3.08 (d, 1H), 2.19 (s, m 3H), 1.72 (td, 1H), 1.22 (m, 3H); MS (ES+) m/z 380 [M+H]+.

1. additionwere mixed in a vial and
2. temperatureWhen cooled to r.t.
3. extractionextracted with DCM (3×3 mL)
4. concentrationThe combined organics were concentrated
5. customthe resulting residue was purified by preparative chromatography
6. additionThe fractions containing the title compound
7. customthe solvent removed in vacuo
8. extractionthe resulting aqueous residue was extracted with DCM (3×3 mL)
9. concentrationconcentrated
10. customdried in a vacuum oven at 40° C. over a weekend