反应详情

A mixture of N-(2,2-diethoxyethyl)carbodiimide (398 mg, 2.51 mmol), 3-amino-4-methyl-phenyl]-3-trifluoromethyl-benzamide (649 mg, 2.20 mmol), methanesulfonic acid (143 μL, 2.20 mmol) in ethanol (25 mL) is heated at reflux for 16 hours. An additional portion of N-(2,2-diethoxyethyl)carbodiimide (525 mg, 3.32 mmol) and methanesulfonic acid (143 μL, 2.20 mmol) are added. After an additional 3 hours refluxing, the reaction mixture is concentrated. The residue is dissolved in HCl (6N, 5 mL) and ethanol (5 mL). After stirring overnight, the reaction mixture is concentrated and basified with 25% NaOH solution to a pH of 14. The mixture is stirred for 30 minutes, extracted with CH2Cl2, dried, concentrated and purified by column chromatography (silica gel, eluting with 7N NH3 in methanol:dichloromethane from 2% to 4%) to give the title compound.

1. temperatureis heated
2. temperatureat reflux for 16 hours
3. temperatureAfter an additional 3 hours refluxing
4. concentrationthe reaction mixture is concentrated
5. dissolutionThe residue is dissolved in HCl (6N, 5 mL)
6. concentrationthe reaction mixture is concentrated
7. stirringThe mixture is stirred for 30 minutes
8. extractionextracted with CH2Cl2
9. customdried
10. concentrationconcentrated
11. custompurified by column chromatography (silica gel, eluting with 7N NH3 in methanol:dichloromethane from 2% to 4%)