反应详情

温度

80 °C

4-(cyclopropylmethyl)benzeneboronic acid (1.5 g), 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (2.99 g) and sodium carbonate (912 mg) were added to a mixture of toluene (66 ml), ethanol (33 ml) and water (24 ml). The mixture was deoxygenated by alternatively bubbling argon through and evacuating (3 cycles) and tetrakis(triphenylphosphine) palladium(0) (347 mgs) was added. The reaction mixture was heated to 80° C. for 18 hours with efficient stirring and, after cooling, ethyl acetate (50 ml) and water (30 ml) were added. The organic phase was separated and the aqueous layer extracted with ethyl acetate (2×30 ml). The combined organic phases were washed with brine (15 ml), dried (MgSO4) and evaporated. The residue was purified by chromatography on a Mega Bond Elut column, eluting with a gradient of ethyl acetate in hexane (0-100%) to give 2-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (1.85 g); 1H NMR (d6 -DMSO): 0.25 (q, 2H), 0.54 (m, 2H), 1.03 (M, 1H), 1.64 (m, 1H), 2.55 (s, 3H), 2.60 (d, 2H), 3.83 (d, 2H), 3.98 (s, 3H), 7.33 (d, 2H), 7.46 (d, 2H), 7.77 (dd, 1H), 8.15 (s, 1H), 8.10-8.95 (m, 2H); mass spectrum (+ve ESP) 511 (M+H)+.

1. customThe mixture was deoxygenated by alternatively bubbling argon through and
2. customevacuating (3 cycles) and tetrakis(triphenylphosphine) palladium(0) (347 mgs)
3. additionwas added
4. temperatureafter cooling
5. additionethyl acetate (50 ml) and water (30 ml) were added
6. customThe organic phase was separated
7. extractionthe aqueous layer extracted with ethyl acetate (2×30 ml)
8. washThe combined organic phases were washed with brine (15 ml)
9. dry with materialdried (MgSO4)
10. customevaporated
11. customThe residue was purified by chromatography on a Mega Bond Elut column
12. washeluting with a gradient of ethyl acetate in hexane (0-100%)