Lithium hydroxide, monohydrate → HCID 118875472, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 0.06 mmol) in HCOOH (2 mL) was added Zn dust (19.5 mg, 0.3 mmol). The reaction was heated at 100° C. for 1 h then cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was dissolved in water (1 ml) and THF (1 mL). Next LiOH.H2O (25 mg, 0.6 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)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10 mg, 29.4% yield) as clear oil. 1H NMR (CDCl3) δ: 8.65 (s, 1H), 8.40 (s, 1H), 7.78 (d, J=6.8 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.36 (t, J=8.3 Hz, 1H), 7.01 (d, J=8.3 Hz, 1H), 6.81 (dd, J=8.3, 2.2 Hz, 1H), 6.75 (s, 1H), 4.82 (s, 2H), 4.23 (t, J=6.2 Hz, 2H), 3.57 (t, J=5.5 Hz, 2H), 2.93 (s, 1H), 2.00-1.87 (m, 2H). LCMS: MH+ 571 and TR=3.069 min.

Provenance & Evidence