反应详情

A mixture of 6-[4-(5-fluoro-2-trifluoromethylbenzoyl)piperazin-1-yl]imidazo[1,2-b]pyridazine-2-carboxylic acid ethyl ester (0.100 g, 0.215 mmol), isoamylamine (1 mL), and sodium cyanide (0.020 g, 0.408 mmol) was stirred at room temperature over night. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous Na2SO4, concentrated. The residue was purified by column chromatography. The title compound was obtained as a white solid in 85% yield (0.092 g). 1H NMR (300 MHz, CDCl3) δ 8.13 (s, 1H), 7.74-7.7 (m, 1H), 7.65 (d, J=9.9 Hz, 1H), 7.21-7.16 (m, 1H), 6.86 (d, J=9.9 Hz, 1H), 4.02-3.92 (m, 1H), 3.89-3.79 (m, 1H), 3.62-3.54 (m, 2H), 3.49-3.39 (m, 4H), 3.35-3.28 (m, 2H), 1.74-1.6 (m, 1H), 1.53-1.44 (m, 2H), 0.91 (d, J=6.6 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ 165.9, 162.5, 162.4, 154.7, 138.4, 137.0, 136.9, 135.6, 129.7, 129.6, 129.5, 126.4, 125.1, 123.3, 122.9, 122.4, 121.4, 118.1, 116.8, 116.5, 114.9, 114.6, 111.8, 46.2, 46.1, 45.6, 41.2, 38.5, 37.3, 25.7, 22.4. MS (ES+) m/z 507 (M+1).

1. concentrationThe reaction mixture was concentrated in vacuo
2. additiondiluted with ethyl acetate
3. washwashed with water
4. dry with materialThe organic layer was dried over anhydrous Na2SO4
5. concentrationconcentrated
6. customThe residue was purified by column chromatography