Diisopropylamine → 2-acetyl-6-amino-5-bromo-N-methylbenzofuran-3-carboxamide

Temperature

-78 °C

To a solution of diisopropylamine (3.76 g, 37.1 mmol) in THF (25 mL) was slowly added a solution of n-BuLi (2.5 mol/L in hexane) (16.5 mL, 40.5 mmol) under N2 at −78° C. and the resulting solution was stirred at −78° C. for 30 minutes. A solution of compound 6-amino-5-bromo-N-methylbenzofuran-3-carboxamide (2 g, 7.43 mmol) in THF (50 mL) was slowly added to the fresh lithium diisopropylamide at −78° C. and stirred for another one hour. To the resulting mixture was added N-methoxy-N-methylacetamide (3.83 g, 37.16 mmol) at −78° C. and stirred for another one hour. The reaction was quenched with saturated NH4Cl at −78° C. and the mixture was slowly warmed to room temperature. Water was added and the mixture extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product. The crude product was purified by column chromatography to give compound 2-acetyl-6-amino-5-bromo-N-methylbenzofuran-3-carboxamide (700 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 10.00 (s, 1H), 8.76 (s, 1H), 6.86 (s, 1H), 4.54 (s, 2H), 3.00 (d, J=4.8 Hz, 3H), 2.70 (s, 3H). MS (M+H)+: 311/313.

1. stirringstirred for another one hour
2. stirringstirred for another one hour
3. customThe reaction was quenched with saturated NH4Cl at −78° C.
4. temperaturethe mixture was slowly warmed to room temperature
5. additionWater was added
6. extractionthe mixture extracted with EtOAc
7. washThe organic layers were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customto give the crude product
11. customThe crude product was purified by column chromatography

ORD record

ord-bfc4a2731147481c8a5e782297e10d20

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242998B2