3-Chlorophenol → 6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-5-isopentyl-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a solution of 3-(6-bromo-5-isopentyl-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (42 mg, 0.109 mmol) in dioxane (2 mL) was added 3-chlorophenol (28 mg, 0.218 mmol), CuI (6 mg, 0.0327 mmol), Cs2CO3 (71 mg, 0.218 mmol) and 3-(dimethylamino)propanoic acid (3 mg, 0.0327 mmol). The reaction was stirred at 130° C. (MW) for 2 h, cooled to RT then diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4, and concentrated to a residue which was purified by Prep HPLC to give 6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-5-isopentyl-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (8 mg, 15.5% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.57 (s, 1H), 7.39 (t, J=8.4 Hz, 1H), 7.17 (d, J=9.2 Hz, 1H), 7.02-7.00 (m, 1H), 6.93 (dd, J=8.0, 2.4 Hz, 1H), 4.50 (t, J=5.2 Hz, 1H), 4.00 (t, J=7.2 Hz, 2H), 3.58 (s, 3H), 3.45-3.50 (m, 2H), 3.15-3.10 (m, 2H), 1.77-1.72 (m, 2H), 1.57-1.52 (m, 1H), 1.23-1.34 (m, 2H), 0.82 (d, J=6.8 Hz, 6H). LCMS: MH+ 432 and TR=3.366 min.

Provenance & Evidence