1,3-Dibromobenzene → (NZ,3R)-N-[3-(3-bromophenyl)-5-methyl-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 4 mL vial charged with a stir bar, (3R)-3-fluoro-N-(5-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carboxamide (40 mg, 0.17 mmol, Example 34A) was added, followed by copper(I) trifluoromethanesulfonate benzene complex (17 mg, 0.03 mmol), 5-chloro-1,10-phenanthroline (15 mg, 0.07 mmol) and cesium carbonate (61 mg, 0.19 mmol). A loose cap with septum was placed on the vial and then the vial was placed under vacuum in a vacuum oven for 30 minutes. The mixture was purged with nitrogen gas a couple of times. 1,3-Dibromobenzene (47 mg, 0.2 mmol) dissolved in 1-methyl-2-pyrrolidinone (1.0 mL) was added to the mixture. The vial was capped and placed on a heater/stirrer and heated to 120° C. overnight. Then 1 mL of a solution of concentrated ammonium hydroxide/water (1:2) was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid) to provide the title compound.

Provenance & Evidence