Dimethylformamide → N,1-dimethylindole-2-carboxamide

To a stirred solution of ethyl indole-2-carboxylate (25.0 g, 132.1 mmole) in dry DMF (100 mL) at 5° C. was added 60% NaH (6.9 g, 171.7 mmole). After 10 min, methyl iodide (56.2 g, 396.3 mmole) was added and the reaction slurry was allowed to warm RT and stirred for 12 hr. The reaction contents were poured into H2O (200 mL) and extracted with EtOAc (2×150 mL). The combined organic phases were washed sequentially with H2O and brine, then were dried over Na2SO4. Concentration under reduced pressure gave a yellow oil. This oil was suspended in a 40% methylamine/H2O solution (100 mL) containing THF (50 mL) and stirred vigorously at RT for 24 hr. The reaction solution was concentrated under vacuum to remove the THF and then poured into H2O (400 mL). The precipitate was filtered, washed with H2O and dried under vacuum at RT to afford the title compound (23.3 g, 94%) as a white solid: MS (ES) m/e 189 (M+H)+.

1. customThe reaction contents
2. extractionextracted with EtOAc (2×150 mL)
3. washThe combined organic phases were washed sequentially with H2O and brine
4. dry with materialwere dried over Na2SO4
5. concentrationConcentration under reduced pressure
6. customgave a yellow oil
7. stirringstirred vigorously at RT for 24 hr
8. concentrationThe reaction solution was concentrated under vacuum
9. customto remove the THF
10. additionpoured into H2O (400 mL)
11. filtrationThe precipitate was filtered
12. washwashed with H2O
13. customdried under vacuum at RT

ORD record

ord-4da9aa824d97455db6be70f675c16c9c

Source dataset

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06765005B2