反应详情

温度

18.5 °C

5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid, 3.8 g, 25 mmol) is slurried in 40 ml of 2M oxalyl chloride in dichloromethane, and to the slurry are added a few drops of dimethylformamide. The resulting mixture is stirred under a nitrogen atmosphere at 15-22° C. for 10-12 hours. The resulting acid chloride as a dark solution is evaporated to a dry residue. The residue is dissolved in toluene (50 ml) and evaporated once more to give the crude acid chloride. To a stirred mixture of the crude acid chloride in dichloromethane (100 ml) and N,O-dimethylhydroxylamine hydrochloride (2.7 g, 27.5 mmol) at 0-5° C. is added pyridine (4.7 g, 3.2 ml, 60 mmol) dropwise under a nitrogen atmosphere while maintaining the temperature about 0-5° C. The resulting stirred mixture is allowed to warm to 15-20° C. over a period of 4 hours and the reaction is monitored for completion by HPLC (Prodigy ODS3 4.6×150 mm column, using a 10 minutes gradient from 90:10 to 10:90 water/acetonitrile with 0.02% trifluoroacetic acid and UV detection at 254 nm. The retention time of the amide was 1.1 min). The mixture is washed with water (50 ml), concentrated, and purified on a short column of silica gel using elution with chloroform to give upon evaporation of volatiles N-Methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide, 4.1 g, 86%) as a light-brown crystalline solid, m.p. 45-50° C., which is characterized by NMR, mass spectrum, and elemental analysis.

1. customThe resulting acid chloride as a dark solution is evaporated to a dry residue
2. dissolutionThe residue is dissolved in toluene (50 ml)
3. customevaporated once more
4. customto give the crude acid chloride
5. temperaturewhile maintaining the temperature about 0-5° C
6. stirringThe resulting stirred mixture
7. temperatureto warm to 15-20° C. over a period of 4 hours
8. washThe mixture is washed with water (50 ml)
9. concentrationconcentrated
10. custompurified on a short column of silica gel using elution with chloroform