反应详情

温度

100 °C

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.

1. temperaturethen cooled to RT
2. filtrationfiltered
3. concentrationThe filtrate was concentrated
4. customdried to a residue which
5. dissolutionwas dissolved in water (1 ml)
6. extractionthen extracted with EA (3×5 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. concentrationconcentrated to a residue which
9. customwas purified by Prep HPLC