反应详情

温度

120 °C

A mixture of 3-amino-N-cyclopropyl-4-methyl-benzamide 1 (380 mg, 2.0 mmol) in 2.0 mL of triethyl orthoformate was stirred at 120° C. in microwave for 20 minutes. The solvent was removed under reduced pressure. The residue was dissolved in 5 mL of acetic acid and then was added aminomalononitrile p-toluenesulfonate (506 mg, 2.0 mmol) and sodium acetate (164 mg, 2.0 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with 20 mL of water and then its pH was adjusted to 8.0 by aqueous NaOH. The resulting mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo evaporated. The residue was purified by silica gel column chromatography (10/1, methylene chloride:methanol) to give 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide 3 as a colorless solid (170 mg, 30%). HPLC (4 minute gradient) tR=1.39 min; MS m/z 282 [M+H].

1. customThe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in 5 mL of acetic acid
3. stirringThe reaction mixture was stirred at room temperature overnight
4. extractionThe resulting mixture was extracted with EtOAc (3×50 mL)
5. washThe combined organic layers were washed with water (10 mL) and brine (10 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customevaporated
10. customThe residue was purified by silica gel column chromatography (10/1, methylene chloride:methanol)