Lithium Hexamethyldisilazide → N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide (81 mg, 0.261 mmol) in THF (4 mL) was stirred in a bath cooled to −78° C., and n-BuLi (0.22 mL, 0.548 mmol) was added slowly. The cold bath was removed, and the reaction was allowed to stir for 30 min. LHMDS (0.261 mmol) was then added slowly. The suspension was transferred dropwise to a stirring solution of compound 4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzoic acid ethyl ester (81 mg, 0.261 mmol) in THF at 0° C. After 30 min cole MeOH was added and the mixture was partitioned between saturated NH4Cl and EtOAc, then extracted with EtOAc (3×). The organic combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated, and chromatographed (1% MeOH (with 5% NH4OH)/CH2Cl2 to 5% MeOH (with 5% NH4OH)/CH2Cl2) to afford N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzamide (47 mg, 33%) as an orange foam: ESI MS m/z=537 [C27H32N6O4S+H]+.

Provenance & Evidence