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

Participants

Reaction Steps

To a mixture of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (80 mg, 0.17 mmol), CuI (4.2 mg, 0.022 mmol), Cs2CO3 (167.6 mg, 0.51 mmol) and 2-(dimethylamino)acetic acid (8.8 mg, 0.085 mmol) in dioxane (2 mL) was added 3-chlorophenol (55.1 mg, 0.43 mmol). The reaction was heated at 140° C. (MW) for 2 h, cooled to RT then diluted with EA (15 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10.2 mg, 12% yield) as a white solid. 1H NMR (CDCl3) δ: 8.35 (s, 1H), 7.23 (d, J=8.2 Hz, 1H), 7.17 (s, 4H), 7.09 (d, J=8.0 Hz, 1H), 6.84-6.73 (m, 2H), 4.71 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.55 (s, 2H), 3.02 (s, 1H), 2.00-1.86 (m, 2H). LCMS: MH+ 486 and TR=3.332 min.

Provenance & Evidence