Acetohydrazide → 3-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-7-carboxylic acid

Dissolved commercially available ethyl 2-oxopyrrolidine-3-carboxylate (2.50 g, 15.91 mmol) in 30 mL dichloromethane in 50 mL round bottom flask. To this solution was added trimethyloxonium tetrafluoroborate (2.59 g, 17.5 mmol) as a solid and rinsed with 20 mL dichloromethane. The resulting mixture was stirred at room temperature for two h and LC/MS indicated that the intermediate methyl 5-methoxy-3,4-dihydro-2H-pyrrole-4-carboxylate had formed. At this point, acetohydrazide (1.18 g, 15.91 mmol) was introduced as a solid to the mixture and the resulting solution was stirred at room temperature for 3 h. The solution was then concentrated under vacuum to remove all dichloromethane and the residue was then taken up in 100 mL n-butanol which was heated to reflux in an oil bath set at 120° C. overnight. The solution was cooled to room temperature and concentrated under vacuum. The residue was purified via sixteen 1500 μm silica gel preparative plates eluting with 90:10 dichloromethane:methanol solvent system. The product was extracted from the silica gel using 85:15 dichloromethane:methanol which afforded the title compound (454 mg, 11%). 1H NMR (500 MHz DMSO-d6) δ: 4.16-4.06 (m, 1H), 4.00-3.88 (m, 1H), 2.85-2.78 (m, 1H), 2.29 (s, 3H), 1.55 (dt, J=6.7, 13.9 Hz, 2H), 1.32 (dt, J=6.7, 14.0 Hz, 2H), 0.88 (t, J=7.5 Hz, 3H). LC-MS: m/z (ES)=196 (MH)+.

1. washrinsed with 20 mL dichloromethane
2. customhad formed
3. stirringthe resulting solution was stirred at room temperature for 3 h
4. concentrationThe solution was then concentrated under vacuum
5. customto remove all dichloromethane
6. temperaturewas heated
7. temperatureto reflux in an oil bath
8. temperatureThe solution was cooled to room temperature
9. concentrationconcentrated under vacuum
10. customThe residue was purified via sixteen 1500 μm silica gel preparative plates
11. washeluting with 90:10 dichloromethane
12. extractionThe product was extracted from the silica gel using 85:15 dichloromethane

ORD record

ord-cea3dfcac84345a78be7f1bce7971b4c

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653260B2