8-Chloro-10-(trifluoromethyl)pyrimido[5,4-b]quinolin-4(3H)-one → 10-Butyl-8-chloro-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

8-Chloro-10-(trifluoromethyl)pyrimido[5,4-b]quinolin-4(3H)-one (7, 87 mg, 0.290 mmol) was suspended in anhydrous THF-TMEDA (10:1, 2 mL) and cooled to −78° C. under a nitrogen atmosphere. n-BuLi (1.6M 0.73 mL, 4 equiv) was added dropwise over 10 minutes. After the addition was complete, the reaction was stirred for 20 minutes at −78° C. and then warmed to rt over 45 minutes. The reaction was quenched with sat. NH4Cl solution and then partitioned between H2O and EtOAc. The aqueous layer was extracted with EtOAc (2×) and Et2O (2×). The combined organic phases were dried over Na2SO4 and concentrated. Chromatography (SiO2, 50% EtOAc-hexane) afforded the desired material 8 as a tan solid (35.4 mg, 34%). Rf 0.34 (50% Ethyl acetate-hexane). 1H NMR (CDCl3, 300 MHz) δ 11.42 (br s, NH), 7.78 (s, 1H), 7.30 (m, 1H), 7.18 (dd, J=2.2, 8.5 Hz, 1H), 6.95 (br s, NH), 6.77 (d, J=8.5 Hz, 1H), 2.75 (m, 1H); 2.12 (m, 1H), 1.28 (m, 2H), .0.95 (m, 2H), 0.79 (t, J=7.4 Hz, 3H). ESI-HRMS 358.0935 (M++H, C16H15ClON3F3 requires 358.0934).

Provenance & Evidence