反应详情

A vial was charged with perfluorophenyl 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (INTERMEDIATE TTTT; 71.85 mg, 0.118 mmol), 1,2,4-thiadiazol-5-amine (13.10 mg, 0.130 mmol), and cesium carbonate (115 mg, 0.353 mmol). The vial was flushed with Ar (g), and then acetonitrile (589 μl) was added. After 2 h, the mixture was diluted with EtOAc and 0.5 N aq. HCl. The layers were separated, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from DCM/MeOH. The residue was then taken up in MeOH and filtered. The collected solid was washed with MeOH (1×), dried under a stream of N2 (g), then dried under vacuum to give 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (40 mg, 0.076 mmol, 64.4% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.72 (d, J=5.7 Hz, 1H), 8.60 (d, J=1.7 Hz, 1H), 8.48 (s, 1H), 8.16 (d, J=5.7 Hz, 1H), 7.95-7.90 (m, 1H), 7.88-7.81 (m, 1H), 7.63-7.54 (m, 2H), 7.50-7.41 (m, 2H), 7.36-7.29 (m, 1H), 7.27 (s, 1H), 3.71 (s, 3H). m/z (ESI) 527.2 (M+H)+.

1. customThe vial was flushed with Ar (g)
2. additionacetonitrile (589 μl) was added
3. additionthe mixture was diluted with EtOAc and 0.5 N aq. HCl
4. customThe layers were separated
5. extractionthe aq. layer was extracted with EtOAc (2×)
6. dry with materialThe combined organic extracts were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. concentrationThe residue was concentrated from DCM/MeOH
10. filtrationfiltered
11. washThe collected solid was washed with MeOH (1×)
12. dry with materialdried under a stream of N2 (g)
13. customdried under vacuum