反应详情

温度

100 °C

A mixture of (R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-5(6H)-thione (311,100 mg, 0.3 mmol), (S)—O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine (194 mg, 1.2 mmol), Hg(OAc)2 (192 mg, 0.6 mmol) and anhydrous toluene (2 mL) was heated at 100° C. for 1 h. LCMS shows completion of the reaction. The mixture was cooled, filtered through celite and washed with ethyl acetate. Filtrate concentrated and the resulting oily residue was purified by preparative LCMS to afford (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (35A, 87 mg, 65%) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 1.35 (s, 3H) 1.40 (s, 3H) 2.01 (qd, J=6.32, 3.03 Hz, 2H) 2.76 (s, 3H) 2.95 (dd, J=16.42, 8.84 Hz, 1H) 3.18 (dd, J=17.18, 5.05 Hz, 1H) 3.56-3.62 (m, 1H) 4.09 (dd, J=7.96, 5.94 Hz, 1H) 4.16-4.28 (m, 2H) 4.98 (ddd, J=8.78, 4.61, 1.52 Hz, 1H) 7.07 (td, J=8.21, 2.53 Hz, 1H) 7.34 (dd, J=8.08, 2.53 Hz, 1H) 7.68 (dd, J=12.00, 6.95 Hz, 1H). MS (ES) [M+H] calculated for C2iH26BrFN5O3, 494.11; found 494.00.

1. customcompletion of the reaction
2. temperatureThe mixture was cooled
3. filtrationfiltered through celite
4. washwashed with ethyl acetate
5. concentrationFiltrate concentrated
6. customthe resulting oily residue was purified by preparative LCMS