5-Bromo-1-methyl-1H-imidazole → (1-Methyl-1H-imidazol-5-yl)(2-methylbenzo[d]oxazol-5-yl)methanone

Participants

Reaction Conditions

Reaction Steps

To a flask containing 5-bromo-1-methyl-1H-imidazole (700 mg, 4.35 mmol) was added THF (14 mL) and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropylmagnesium chloride-LiCl complex (1.3 M in THF, 3.4 mL, 4.38 mmol) which resulted in a white suspension. The reaction was stirred at 0° C. for 25 min, then a THF solution (5 mL) of (N-methoxy-N,2-dimethylbenzo[d]oxazole-5-carboxamide (700 mg, 3.20 mmol, Intermediate 43, step a) was introduced and the mixture was allowed to warm to room temperature. The reaction was heated to 40° C. for 20 hours and then quenched with a saturated NH4Cl solution. The aqueous portion was extracted with EtOAc (4×50 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was triturated with DCM-Et2O (1:10) to afford the title compound as an amber solid. The mother liquors were concentrated and again triturated with Et2O to provide a second crop of the material. Finally, the mother liquors were concentrated and chromatographed on silica gel (10-50% acetone-DCM increasing gradient to 5% MeOH-DCM) to provide the title compound as a pale yellow solid.

Provenance & Evidence