反应详情

A mixture of 3-cyclohexyl-N-[(dimethylamino)sulfonyl]-2-(2-formylphenyl)-1H-indole-6-carboxamide (1.06 g, 2.1 mmol), methyl 2-(dimethoxyphosphoryl)acrylate (0.4 mL, 3.2 mmol), and Cs2CO3 (1.04 g, 3.2 mmol) in DMF (4 mL) was stirred at 60° C. for 18 hr, at which time additional Cs2CO3 4 g, 0.32 mmol) and methyl dimethoxyphosphoryl)acrylate (0.4 mL, 3.2 mmol) were added. The mixture was stirred for an additional 8 hr, cooled and diluted with ethyl acetate. The resulting mixture was washed with dilute HCl (3×) followed by brine (3×). The solution was concentrated to leave the crude product as a yellow solid (1.2 g). The crude product was purified utilizing a Biotage apparatus with a prepacked silicic acid column and using gradients of hexanes:ethyl acetate:acetic acid of from (100:2:0.0.5) to (64:36:0.5). The product containing fractions were combined and concentrated to dryness to afford the titled compound as a pale yellow solid (640 mg, 59%). MS m/z 522 (MH+).

1. additionwere added
2. temperaturecooled
3. washThe resulting mixture was washed with dilute HCl (3×)
4. concentrationThe solution was concentrated
5. customto leave the crude product as a yellow solid (1.2 g)
6. customThe crude product was purified
7. additionThe product containing fractions
8. concentrationconcentrated to dryness