反应详情

温度

80 °C

A mixture of 4-bromoisoquinolin-1-amine (126 mg, 0.565 mmol), bispinacol ester boronate (358 mg, 1.41 mmol), and potassium acetate (333 mg, 3.39 mmol) in 1,4-dioxane (4.6 mL) was sparged with N2 for 10 min. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (23.1 mg, 0.0282 mmol) was added. The mixture was sealed under N2 and heated at 80° C. for 20 h, diluted with DCM, the contents were filtered, washed with DCM, and concentrated. The crude product was mixed with 2-(4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide (124 mg, 0.282 mmol), a 1 M solution of sodium carbonate (0.85 mL) and 1,4-dioxane (3.4 mL, 44 mmol). The mixture was sparged with N2 for 10 min. Palladium acetate (6.342 mg, 0.02825 mmol) and a 1.0 M solution of tri-tert-butylphosphine in toluene (0.0565 mL) were added. The mixture was sealed under N2 and heated at 85° C. for 6 h, diluted with DCM, the contents were filtered, and concentrated. The residue was purified with flash chromatography. The fractions containing the desired product were collected, concentrated, and purified with reverse-phase HPLC to give 108 (25 mg, 16%). LCMS: M+H+=467. 1H NMR (400 MHz, CDCl3) δ 8.91 (d, J=8.6, 1H), 8.67 (s, 1H), 7.85 (d, J=8.3, 1H), 7.71-7.64 (m, 1H), 7.53 (t, J=7.3, 1H), 7.34 (s, 1H), 7.10 (s, 1H), 5.29 (s, 2H), 5.20 (s, 1H), 4.10-3.99 (m, 4H), 3.87 (dd, J=9.1, 4.6, 6H), 2.61 (s, 8H), 1.24 (s, 6H)

1. additionwas added
2. customThe mixture was sealed under N2
3. filtrationthe contents were filtered
4. washwashed with DCM
5. concentrationconcentrated
6. customThe mixture was sparged with N2 for 10 min
7. customThe mixture was sealed under N2
8. temperatureheated at 85° C. for 6 h
9. filtrationthe contents were filtered
10. concentrationconcentrated
11. customThe residue was purified with flash chromatography
12. additionThe fractions containing the desired product
13. customwere collected
14. concentrationconcentrated
15. custompurified with reverse-phase HPLC