反应详情

Trimethylsilyl iodide (11.06 ml, 76.25 mmol) was added to a solution of 3-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[4-(methylsulfonyl)phenoxy]benzamide (7.00 g, 15.25 mmol) in dry acetonitrile (100 ml) under argon for 21 h. Water (40 ml) was added to quench the reaction and the acetonitrile was removed in vacuo. The residue was diluted with ethyl acetate (200 ml) and 1M aqueous hydrochloric acid and the organic layer was separated and further washed with 10% w/v aqueous sodium thiosulfate pentahydrate to remove residual iodine. The organic layer was separated, dried (MgSO4), filtered and evaporated and purified by column chromatography (eluting with 3% to 5% methanol: dichloromethane) to give the title compound (5.70 g, 84%) as a white foam. Recrystallisation from hot ethanol (125 mg/ml) afforded the title compound as colourless needles (87% recovery); 1H NMR (300 MHz, CDCl3) δ: 1.33 (d, 3H), 2.10 (t, 1H), 3.08 (s, 3H), 3.78 (m, 2H), 3.82 (s, 3H), 4.57 (m, 1H), 6.80 (m, 2H), 7.15 (m, 3H), 7.25 (m, 2H), 7.93 (d, 2H), 8.43 (s, 1H); m/z 444 (M−H)−.

1. customto quench
2. customthe reaction
3. customthe acetonitrile was removed in vacuo
4. additionThe residue was diluted with ethyl acetate (200 ml) and 1M aqueous hydrochloric acid
5. customthe organic layer was separated
6. washfurther washed with 10% w/v aqueous sodium thiosulfate pentahydrate
7. customto remove residual iodine
8. customThe organic layer was separated
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. customevaporated
12. custompurified by column chromatography (eluting with 3% to 5% methanol: dichloromethane)