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

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(1-hydroxy-3-methylbutyl)-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 (100 mg, 0.04 mmol) in HCOOH (2 mL) was added Zn dust (64 mg, 0.375 mmol). The reaction was heated at 100° C. for 1 h, cooled to RT and filtered. The filtrate was concentrated, dried to a residue then dissolved in THF (1 ml) and water (1 mL). Next LiOH.H2O (33.6 mg, 0.8 mmol) was added and the reaction was stirred at RT for 10 min then extracted with EA (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(5-methylpyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.5 mg, 7% yield) as clear oil. 1H NMR (CDCl3) δ: 8.29 (s, 1H), 8.22 (s, 1H), 8.16 (s, 1H), 6.99 (s, 1H), 4.26 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.56 (d, J=18.8 Hz, 2H), 3.33-3.23 (m, 2H), 3.20 (s, 1H), 2.33 (s, 3H), 1.99-1.92 (m, 2H), 1.68 (dt, J=11.9, 6.0 Hz, 1H), 1.40 (dt, J=10.7, 6.8 Hz, 2H), 0.91 (d, J=6.6 Hz, 6H). LCMS: MH+ 413 and TR=2.549 min.

Provenance & Evidence