反应详情

温度

95 °C

To a degassed suspension of 2-(2-chloro-8-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-6-morpholino-9H-purin-9-yl)ethyl acetate (110 mg, 0.23 mmol), 1-(phenylsulfonyl)-3-indoleboronic acid (83 mg, 0.27 mmol), 2 M Na2CO3 aqueous solution (0.23 mL, 0.46 mmol) in toluene (3 mL) and ethanol (1 mL) was added Pd(PPh3)4 (10 mg, 0.009 mmol). The suspension was then stirred under nitrogen at 95° C. for 18 hours. The reaction mixture was then diluted with EtOAc and water. The layers were then separated. The aqueous layer was extracted three times with EtOAc. The combined organic extracts were washed with water, dried over Na2SO4, filtered and concentrated. The crude mixture was filtered through a pad of silica gel (10% MeOH in DCM) and the filtrate was concentrated to give a yellow paste which was then taken up in ethanol (10 mL). To the solution was added a 1 M aqueous solution of NaOH (2 mL, 2 mmol). After 2 hours of stirring at 65° C., the reaction mixture was concentrated and purified by RP-HPLC to give 107 (32 mg, 40%). LCMS: M+H+=520.3. 1H-NMR (400 MHz, DMSO-d6): δ 11.5 (s, 1H), 8.54 (m, 1H), 8.20 (s, 1H), 8.11 (d, 1H), 7.44 (m, 1H), 7.14 (m, 2H), 4.44 (t, 2H), 4.27 (s, br, 4H), 3.85 (t, 2H), 3.78 (m, 4H), 3.72 (s, 3H), 2.91 (m, 2H), 1.98 (m, 2H), 1.67 (m, 2H), 1.21 (m, 3H), 1.01 (s, 6H)

1. customThe layers were then separated
2. extractionThe aqueous layer was extracted three times with EtOAc
3. washThe combined organic extracts were washed with water
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. filtrationThe crude mixture was filtered through a pad of silica gel (10% MeOH in DCM)
8. concentrationthe filtrate was concentrated
9. customto give a yellow paste which
10. stirringAfter 2 hours of stirring at 65° C.
11. concentrationthe reaction mixture was concentrated
12. custompurified by RP-HPLC