Lithium hydroxide, monohydrate → 3-(3-hydroxypropyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (24 mg, 0.04 mmol) in HCOOH (1 mL) was added Zn dust (13 mg, 0.2 mmol). The reaction was heated at 100° C. for 1 h, cooled to RT and filtered. The filtrate was concentrated to a crude intermediate which was dissolved in THF (2 mL) and water (2 mL) then LiOH.H2O (33.6 mg, 0.8 mmol) was added. The reaction was stirred at RT for 30 min then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (4.0 mg, 20% yield) as a white solid. 1H NMR (CDCl3) δ: 8.68 (s, 1H), 8.38 (s, 1H), 8.27 (s, 1H), 8.17 (d, J=2.4 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.56 (d, J=7.6 Hz, 1H), 6.98 (s, 1H), 4.86 (s, 2H), 4.25 (t, J=6.0 Hz, 2H), 3.74 (s, 3H), 3.57-3.61 (m, 2H), 2.96 (brd s, 1H), 2.34 (s, 3H), 1.92-1.97 (m, 2H). LCMS: MH+ 502 and TR=2.285 min.

Provenance & Evidence