反应详情

温度

65 °C

A mixture of 17-[2-(4-isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid (35, 60 mg, 0.095 mmol) and CDI (0.23 mmol) in dry THF (5 mL) was heated at 65° C. in a reflux setup for 1 h, and then cooled to RT. The formation of the stable intermediate 36 was observed. Then, a solution of lithium bis(trimethylsilyl)amide (460 μL of 1.0M in THF) and N-ethyl-N-methylsulfonamide (62.5 mg, 0.45 mmol) in THF (7 mL), was added. After 1 h, the reaction was quenched with water, evaporated, diluted with THF, acidified with HCl in dioxane, and evaporated. Purification by flash chromatography (YMC silica, gradient MeOH/CH2Cl2, 2 to 5%) gave 9.6 mg of the title product as white solids. LCMS: tR=3.51 min, >95%, m/z (API-ES+)=753 (M+1), 1H NMR (400 MHz, CDCl3) major rotamer □ 1.16-1.28 (m, 5H), 1.36 (m, 1H), 1.39 (d, 6H, J=6.4 Hz), 1.42 (m, 1H), 1.62 (m, 1H), 1.70 (m, 1H), 1.87 (dd, 1H, J=8.2 Hz, 5.8 Hz), 2.00 (m, 1H), 2.20-2.31 (m, 1H), 2.33-2.44 (m, 2H), 2.50-2.62 (m, 2H), 2.88-2.94 (m, 4H), 3.04 (s, 3H), 3.17-3.28 (m, 2H), 3.38-3.45 (m, 3H), 3.97 (s, 3H), 4.60 (m, 1H), 5.04 (m, 1H), 5.37 (m, 1H), 5.66 (m, 1H), 6.23 (s, 1H), 7.04 (d, 1H, J=1.2 Hz), 7.12 (dd, 1H, J=8.8, 2.8 Hz), 7.37 (d, 1H, J=2.8 Hz), 7.51 (m, 1H), 8.03 (d, 1H, J=8.8 Hz), 10.53 (s, 1H).

1. temperaturecooled to RT
2. customthe reaction was quenched with water
3. customevaporated
4. additiondiluted with THF
5. customevaporated
6. customPurification by flash chromatography (YMC silica, gradient MeOH/CH2Cl2, 2 to 5%)