Cesium carbonate → 6-(3-chloro-4-fluorobenzyl)4-[(3-chloro-4-fluorobenzyl)oxy]-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 4-hydroxy-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide (0.018 g, 0.068 mmol) in DMF (2 mL) was treated with Cs2CO3 (0.066 g, 0.2 mmol) and 3-chloro-4-fluoro benzyl bromide (0.045 g, 0.2 mmol) and heated to 40° C. The reaction mixture was then cooled to 0 degrees C., a suspension of NaH (95% dispersion in oil, 0.2 mmol) was added and the reaction was warmed to room temperature. After 1 hr the reaction was partitioned between ice water and EtOAc, the organic layer was dried with brine and Na2SO4, filtered and evaporated to give 6-(3-chloro-4-fluorobenzyl)4-[(3-chloro-4-fluorobenzyl)oxy]-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide (ES MS M+1=549.9). This material was then dissolved in CH2Cl2 (3 mL) and treated with 4 drops of a 30% by weight solution of HBr in propionic acid at room temperature. After 20 minutes the solution was concentrated and purified by reverse phase chromatography to give the product.

Provenance & Evidence