反应详情

Molecular sieves (4 Å, powdered, 200 mg) were added to a suspension of 1-(cyclohexyl)methyl-N-hydroxy-7-methoxy-1H-indole-3-carboxamidine (250 mg, 0.829 mmol) in tetrahydrofuran (6 ml) under nitrogen, and the mixture was stirred at room temperature for 30 min. Sodium hydride (60% suspension in oil, 36 mg, 0.900 mmol) was added, then the resulting mixture was stirred at 60° C. for 20 min. The reaction mixture was cooled to room temperature and N,N-dimethylglycine methyl ester (194 mg, 1.66 mmol) was added to the mixture. The resulting mixture was stirred at reflux temperature for 2 h and then concentrated in vacuo. The obtained residue was mixed with dichloromethane (200 ml), washed with 5% aqueous sodium carbonate, dried over magnesium sulfate and concentrated in vacuo. The obtained oil was purified by flash column chromatography eluting with 0.6% (v/v) methanol in dichloromethane to afford an oil. This oil was dissolved in isopropanol (3 ml), then hydrogen chloride (1M solution in diethyl ether; 3 ml) was added to the solution. The resulting mixture was concentrated in vacuo to afford the title compound (1:1 hydrochloride salt) (66 mg).

1. stirringthe resulting mixture was stirred at 60° C. for 20 min
2. temperatureThe reaction mixture was cooled to room temperature
3. stirringThe resulting mixture was stirred
4. temperatureat reflux temperature for 2 h
5. concentrationconcentrated in vacuo
6. additionThe obtained residue was mixed with dichloromethane (200 ml)
7. washwashed with 5% aqueous sodium carbonate
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customThe obtained oil was purified by flash column chromatography
11. washeluting with 0.6% (v/v) methanol in dichloromethane
12. customto afford an oil
13. concentrationThe resulting mixture was concentrated in vacuo