反应详情

温度

95 °C

A solution of 3-dimethylamino-1-(2,4-dichlorophenyl)-2-(4-chlorophenyl)prop-2-en-1-one (14.4 mmol assumed) from Step A, cyanoacetamide (1.33 g, 15.8 mmol), and methanol (1.3 mL, 32 mmol) in DMF (35 mL) was added dropwise to a suspension of sodium hydride (60% in mineral oil) (1.45 g, 36 mmol) in DMF (16 mL) at rt. After the slow addition was complete, the reaction was heated to 95° C. for 2.5 h. Most of the DMF was then removed in vacuo before the reaction was diluted with aqueous 18% citric acid solution. The mixture was extracted twice with methylene chloride and the organic layers were washed with a portion of brine. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The solid residue was triturated with ether, filtered, and air dried to afford 6-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3-nitrile. HPLC/MS: 375 (M+1), 377 (M+3); Rt=3.47 min; 1HNMR (CDCl3): δ 6.96 (br d, J=8.4 Hz, 2H), 7.14 (d, J=8.2 Hz, 1H), 7.25 (br d, J=8.4 Hz, 2H), 7.31 (dd, J=1.9 and 8.2 Hz, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.996 (s, 1H).

1. additionAfter the slow addition
2. customMost of the DMF was then removed in vacuo before the reaction
3. additionwas diluted with aqueous 18% citric acid solution
4. extractionThe mixture was extracted twice with methylene chloride
5. washthe organic layers were washed with a portion of brine
6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe solid residue was triturated with ether
9. filtrationfiltered
10. customair dried