Potassium Phosphate, Tribasic → 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)benzyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

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 (See Compound 48, step 2, 60 mg, 0.144 mmol) in dioxane (4 mL) was added 4,4,5,5-tetramethyl-2-(3-(trifluoromethoxy)benzyl)-1,3,2-dioxaborolane (90 mg, 0.288 mmol), Pd(dppf)Cl2 (10 mg) and aq. 2M K3PO4 (0.8 mL). The reaction was heated at 85° C. for 2 h, cooled to RT and filtered. The filtrate was concentrated, dried to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)benzyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 28.7% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.61 (s, 1H), 7.43 (t, J=7.9 Hz, 1H), 7.19 (dd, J=25.5 and 8.5 Hz, 3H), 4.47 (s, 1H), 4.16 (s, 2H), 4.03-3.89 (m, 2H), 3.57 (s, 3H), 3.45 (dd, J=11.0 and 6.0 Hz, 2H), 3.12 (d, J=6.0 Hz, 2H), 1.81-1.64 (m, 2H), 1.51-1.56 (m, 1H), 1.03 (d, J=9.5 Hz, 2H), 0.81 (d, J=6.6 Hz, 6H). LCMS: MH+ 480 and TR=3.320 min.

Provenance & Evidence