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

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-hydroxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.1 g, 6.3 mmol) in DMF (20 mL) was added isopropyl iodide (2.14 g, 12.6 mmol) followed by K2CO3 (1.74 g, 12.6 mmol). The reaction was heated at 80° C. for 2 h, cooled to RT, diluted with water (100 mL) then extracted with EA (3×100 mL). The combined organic layers were washed with water (100 mL) then brine (100 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography to give 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (1.08 g, 46% yield over 3 steps) as a solid. 1H NMR (CDCl3) δ: 8.34 (d, J=3.1 Hz, 1H), 7.90 (d, J=3.1 Hz, 1H), 4.69-4.51 (m, 2H), 4.10-4.30 (m, 2H), 3.90-3.78 (m, 2H), 3.69 (s, 3H), 3.51), 3.40-3.70 (m, 2H), 2.01 (dd, J=13.4, 6.7 Hz, 2H), 1.86-1.45 (m, 6H), 1.38 (d, J=6.1 Hz, 6H), 1.26 (t, J=7.1 Hz, 2H). LCMS: [MH+-THP] 294 and TR=1.668 min.

Provenance & Evidence