反应详情

A suspension of 308.3 mg (2.0 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 522.7 mg (2.0 mmol) of 2-(1H-benzimidazol-2-ylsulfanyl)-thiazole-5-carbaldehyde (obtained from step 1) in 10 mL of n-butanol under argon is stirred at room temperature for 0.5 hour. 1,3-Cyclohexanedione (224.3 mg, 2.0 mmol) is then added and the reaction mixture is heated at reflux temperature for 2 h. The mixture is then cooled to room temperature and concentrated under reduced pressure. The residue is purified by chromatography on a prepacked 70 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. The residue is triturated in ethanol, filtered, washed with diethylether and dried under reduced pressure. 313 mg of 9-[2-(1H-benzimidazol-2-ylsulfanyl)-thiazol-5-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester are obtained as a yellow powder. mp: 194° C. LCMS: m/z 492: [M+H]+ (base peak); m/z 490: [M−H]− (base peak).

1. temperaturethe reaction mixture is heated
2. temperatureat reflux temperature for 2 h
3. temperatureThe mixture is then cooled to room temperature
4. concentrationconcentrated under reduced pressure
5. customThe residue is purified by chromatography on a prepacked 70 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate; rate: 40 mL/min)
6. additionThe fractions containing the desired product
7. concentrationconcentrated to dryness under reduced pressure
8. customThe residue is triturated in ethanol
9. filtrationfiltered
10. washwashed with diethylether
11. customdried under reduced pressure