反应详情

温度

130 °C

A vial was charged with 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate GG; 0.200 g, 0.624 mmol), Pd2(dba)3 (0.029 g, 0.031 mmol), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (0.027 g, 0.062 mmol), 3-(3-fluorophenyl)piperidine hydrochloride (0.202 g, 0.935 mmol) and sodium tert-butoxide (0.240 g, 2.494 mmol). Dioxane (6.24 ml) was added and the reaction was flushed with argon and stirred at 130° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM) to afford 1-(3-(3-fluorophenyl)piperidin-1-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.57 (s, 1H), 8.48 (s, 1H), 8.29-8.25 (m, 1H), 8.23 (d, J=9.0 Hz, 1H), 8.19 (d, J=5.7 Hz, 1H), 7.95 (dd, J=1.8, 8.9 Hz, 1H), 7.57 (d, J=5.8 Hz, 1H), 7.35 (dt, J=6.5, 8.0 Hz, 1H), 7.25-7.16 (m, 2H), 7.08-6.97 (m, 2H), 3.79 (t, J=13.0 Hz, 2H), 3.21-3.10 (m, 1H), 3.08-2.91 (m, 2H), 2.09-1.99 (m, 1H), 1.97-1.83 (m, 2H), 1.79-1.65 (m, 1H). m/z (ESI) 464.2 (M+H)+.

1. customthe reaction was flushed with argon
2. additionThe reaction was diluted with ethyl acetate
3. washwashed with water
4. extractionThe aqueous layer was extracted with ethyl acetate
5. dry with materialthe combined organic layers were dried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM)