反应详情

A degassed suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (4.8 g, 12.4 mmol), zinc cyanide (1.2 g, 10.2 mmol), and Pd(PPh3)4 (1.6 g, 1.36 mmol) in dimethylformamide (14 mL) was subjected to microwave irradiation at 190° C. for 20 minutes. This procedure was repeated seven times and all the reaction mixtures were combined and concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was separated and extracted with ethyl acetate three times. The combined organic extracts were washed with water and then brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (silica, gradient 0% to 100%, diethyl ether in pentane) to afford the title compound as a yellow solid (18.2 g). LCMS (method B): RT=4.74 min, M+H+=344.

1. customirradiation at 190° C. for 20 minutes
2. customthe reaction mixtures
3. concentrationconcentrated in vacuo
4. dissolutionThe resultant residue was dissolved in ethyl acetate
5. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
6. customThe aqueous layer was separated
7. extractionextracted with ethyl acetate three times
8. washThe combined organic extracts were washed with water
9. dry with materialbrine, dried (Na2SO4)
10. filtrationfiltered
11. customevaporated in vacuo