Bromotrichloromethane → 5-Bromo-2-(3-chloro-4-fluorobenzyl)-8-methoxy-3,4-dihydro-2,6-naphthyridin-1(2H)-one

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Reaction Steps

A suspension of 6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid (3.5 g, 9.59 mmol; Example 12, step 12) in anhydrous dichloromethane (60 mL) and anhydrous DMF (0.45 mL) at room temperature was treated with oxalyl chloride (1.7 mL, 19.2 mmol). The reaction mixture was stirred at room temperature for 2 hours and concentrated under vacuum. A solution of the residue and AIBN (0.47 g, 2.88 mmol) in anhydrous dichloromethane (30 mL) was added portionwise to a solution of 2-pyridinethiol-N-oxide (2.4 g, 19.2 mmol) in a mixture of bromotrichloromethane (90 mL) and dichloroethane (30 mL) at 100° C. over a period of 20 minutes (Barton et al, Tetrahedron Lett., 5939, 1985). The mixture was heated at the same temperature for 20 minutes, cooled to room temperature, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 2% methanol in dichloromethane. Collection and concentration of appropriate fractions provided the titled compound.

Provenance & Evidence