Potassium Fluoride → 5-(4-amino-2,5-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

Temperatur

25 °C

4-Bromo-2,5-difluoroaniline (0.1 g, 4.85 mmol), 1-methyl-5-cyano-2-pyrrole-boronic acid (1.3 g, 8.7 mmol), KF (0.93 g, 16 mmol), and Pd2(dba)3 (117 mg, 0.12 mmol) were added to a 50 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (12.1 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes) (0.72 mL, 0.24 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 16 hours. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane) afforded 5-(4-amino-2,5-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile as a white solid (0.87 g, 77%).

1. customThe flask was sealed
2. custompurged with nitrogen for 5 minutes
3. additionTHF (12.1 mL) was added
4. customthe mixture was purged with nitrogen for an additional 5 minutes
5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (0.72 mL, 0.24 mmol) was added via syringe
6. additionThe mixture was diluted with 250 mL of EtOAc
7. filtrationfiltered through a plug of silica gel
8. washwashed with 200 mL of EtOAc
9. concentrationconcentrated
10. customto give a crude brown/black semi-solid
11. customPurification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane)

ORD-Eintrag

ord-843b3fad7be5403da56aad780ca5d97d

Quelldatensatz

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07291643B2