Ammonium Chloride → (2,6-Dimethylpyridin-3-yl)(1-methyl-1H-imidazol-5-yl)methanone

Temperature

0 °C

To a flask containing 5-bromo-1-methyl-1H-imidazole (360 mg, 2.24 mmol) was added THF and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 2.3 mL, 2.98 mmol) which resulted in a white suspension. The reaction mixture was stirred at 0° C. for 30 min, and a THF (2 mL) solution of N-methoxy-N,2,6-trimethylnicotinamide (522 mg, 2.69 mmol, Intermediate 40, step a) was introduced and the mixture was allowed to warm to room temperature for 3 hours and then heated to 50° C. for 20 hours. The contents were cooled to room temperature, poured into a saturated NH4Cl solution and extracted with EtOAc (4×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. Flash chromatography on silica gel (25-50% Acetonitrile-DCM increasing gradient to 5% MeOH-DCM) afforded the title compound as a pale yellowish solid.

1. additionTo this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 2.3 mL, 2.98 mmol) which
2. customresulted in a white suspension
3. temperatureto warm to room temperature for 3 hours
4. temperatureheated to 50° C. for 20 hours
5. temperatureThe contents were cooled to room temperature
6. extractionextracted with EtOAc (4×50 mL)
7. washThe combined organics were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-14d7a1cd08234dbbac0aca8556928b68

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2