3,4-dihydro-2H-pyran → 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a solution of 6-bromo-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6.2 g, 19.8 mmol) in DCM (100 mL) at 0° C. was added 3,4-dihydro-2H-pyran (6 mL, 65.7 mmol) and pyridinium p-toluenesulfonate (50 mg, 0.2 mmol). The reaction was stirred at RT for 16 h then diluted with DCM (100 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (8:1 to 2:1) to give 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.5 g, 31.8% yield) as a white solid. 1H NMR (CDCl3) δ: 8.68 (m, 1H), 8.54-8.53 (m, 1H), 4.57 (s, 1H), 4.26-4.17 (m, 2H), 3.87-3.80 (m, 2H), 3.68 (s, 3H), 3.52-3.47 (m, 2H), 2.04-1.97 (m, 2H), 1.76-1.63 (m, 2H), 1.49-1.46 (m, 2H). LCMS: [MH+-THP] 314 and TR=1.626 min.

Provenance & Evidence