Selectfluor → Tak-733

Participants

Reaction Steps

To a solution of (R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 6) (1 g, 2.06 mmol, 1 eq) in DMF (19 mL) was added dropwise a mixture of Selectfluor (801 mg, 2.26 mmol, 1.1 eq) in acetonitrile (9 mL) and DMF (5 mL) at ambient temperature while stirring under nitrogen. The reaction mixture was stirred for 10 minutes at ambient temperature and filtered. The filtrate was purified by preparatory LC/MS (30-55% CH3CN in H2O) to give (R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 18) as an off-white solid. The recovered starting material was subjected to the same reaction conditions to produce a second crop of product. The total yield of product was 347 mg (33% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.36-3.40 (m, 1 H) 3.43-3.50 (m, 1 H) 3.58 (s, 3 H) 3.61-3.72 (m, 1 H) 3.72-3.82 (m, 1 H) 4.27-4.37 (m, 1 H) 4.78-4.87 (m, 1 H) 5.14 (d, J=5.81 Hz, 1 H) 6.93-7.03 (m, 1 H) 7.53 (d, J=8.84 Hz, 1 H) 7.65-7.74 (m, 1 H) 8.52 (s, 1 H) 10.25 (d, J=1.01 Hz, 1 H). [M+H] calc'd for C17H15F21N4O4, 505; found, 505.

Provenance & Evidence