反应详情

Dissolve 2-amino-5-ethyl-thiophene-3-carbonitrile (8.2 g, 54 mmol) and 2,4-difluoronitrobenzene (8.6 g, 54 mmol) in tetrahydrofuran (20 ml) and add to a stirring solution of sodium hydride (50% dispersion in mineral oil)(4.1 g, 1.4 equiv) in tetrahydrofuran (50 ml) under a nitrogen atmosphere. Maintain the rate of addition to keep the temperature below 45° C. and gas evolution under control. Stir 18 h. Pour the mixture into a mixture of ice and 2NHCl, extract into ethyl acetate, dry (MgSO4) and concentrate under reduced pressure. Dissolve in ethanol (100 ml) and collect 2-(5-fluoro-2-nitro-phenylamino)-5-ethyl-thiophene-3-carbonitrile by filtration as a yellow solid (7.9 g, 50%): mass spectrum (LCMS) 292 (M+1), 314 (M+Na). NMR (1H, 300 MHz, CDCl3): δ 9.7 (1H broad), 8.25 (1H,m), 6.80 (1H, s), 6.75 (1H,dd), 6.65 (1H, s), 2.80 (2H,q), 1.35(3H,t).

1. temperatureMaintain
2. additionthe rate of addition
3. customthe temperature below 45° C. and gas evolution
4. additionPour the mixture
5. additioninto a mixture of ice and 2NHCl
6. extractionextract into ethyl acetate
7. dry with materialdry (MgSO4)
8. concentrationconcentrate under reduced pressure
9. dissolutionDissolve in ethanol (100 ml)
10. customcollect 2-(5-fluoro-2-nitro-phenylamino)-5-ethyl-thiophene-3-carbonitrile
11. filtrationby filtration as a yellow solid (7.9 g, 50%)