5-Bromo-1-methyl-1H-imidazole → (2,4-Dimethylthiazol-5-yl)(1-methyl-1H-imidazol-5-yl)methanone

Temperature

0 °C

To a flask containing 5-bromo-1-methyl-1H-imidazole (390 mg, 2.42 mmol) was added THF (8 mL) and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M in THF, 2.5 mL, 3.25 mmol) which resulted in a white suspension. The mixture was stirred at 0° C. for 30 min, then a THF solution (2 mL) of N-methoxy-N,2,4-trimethylthiazole-5-carboxamide (550 mg, 2.75 mmol, Intermediate 41, step a) was introduced and the mixture was allowed to warm to room temperature. After 3 hours at room temperature the mixture was heated to 50° C. for 18 hours, followed by quenching with NH4Cl solution. The aqueous portion was extracted with DCM (4×50 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (25-50% EtOAc-DCM increasing gradient to 5% MeOH-DCM) provided the title compound as an amber solid.

1. customresulted in a white suspension
2. temperatureto warm to room temperature
3. temperatureAfter 3 hours at room temperature the mixture was heated to 50° C. for 18 hours
4. customby quenching with NH4Cl solution
5. extractionThe aqueous portion was extracted with DCM (4×50 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-0e14c3dbaba24135ae7421fd19ce64a3

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2