反应详情

To a solution of (S)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 5) (1.25 g, 2.58 mmol, 1 eq) in DMF (26 mL) was added a mixture of Selectfluor (1.187 g, 3.35 mmol, 1.3 eq) in acetonitrile (26 mL). The reaction mixture was irradiated with microwave at 82° C. for 10 minutes and filtered. The filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O) to give (S)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 19) as an off-white solid (331 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.36-3.42 (m, 1H) 3.42-3.51 (m, 1H) 3.59 (s, 3H) 3.63-3.72 (m, 1H) 3.73-3.81 (m, 1H) 4.32 (dd, J=13.14, 3.03 Hz, 1H) 4.79 (br. s., 1H) 5.10 (br. s., 1H) 6.98 (td, J=8.46, 5.31 Hz, 1H) 7.52 (dd, J=8.46, 1.14 Hz, 1H) 7.68 (dd, J=10.36, 1.77 Hz, 1H) 8.51 (s, 1H) 10.24 (d, J=2.27 Hz, 1H). [M+H] calc'd for C17H15F21N4O4, 505. found, 505.

1. customThe reaction mixture was irradiated with microwave at 82° C. for 10 minutes
2. filtrationfiltered
3. customThe filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O)