Hydrochloride methanol → 5-((4-chlorophenyl)(hydroxy)methyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a solution of 5-((4-chlorophenyl)(hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 0.087 mmol) in MeOH (2 mL) was added saturated HCl/MeOH (2 mL, MeOH was saturated by HCl gas at 0° C.). The reaction was stirred at RT for 18 h, concentrated then diluted with EA (10 mL) and aq. NaHCO3 (3 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-((4-chlorophenyl)(hydroxy)methyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (15 mg, 35% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.61 (s, 1H), 7.48-7.35 (m, 2H), 7.24-7.15 (m, 3H), 7.11-6.96 (m, 3H), 6.74 (m, 0.3H), 6.35 (m, 0.8H), 6.10 (m, 0.3H), 5.66 (m, 0.7H), 3.93 (m, 2H), 3.68 (s, 3H), 3.38 (m, 2H), 2.72 (m, 1H), 1.64 (m, 2H), 1.15 (d, J=6.8 Hz, 2H), 1.08 (m, 3H), 0.81 (d, J=6.7 Hz, 1H). LCMS: [M+ —OH] 476 and TR=2.931 min.

Provenance & Evidence