Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate → Methyl 5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy[1,6]-naphthyridine-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 5-bromo-8-hydroxy[1,6]naphthyridine-7-carboxylate (0.28 g, 1.0 mmol), 5-methyl-1,2,5-thiadiazepan-4-one 1,1-dioxide from step 2 (0.178 g, 1.0 mmol) and copper (I) oxide (0.143 g, 1.0 mmol) in pyridine (5 mL) was heated in an oil bath at 115° C. overnight. The resultant mixture was filtered, and the filtrate concentrated under vacuum. The residue was treated with a mixture of chloroform (50 mL) and ethylenediamine tetraacetic acid, disodium salt (5 g) in water (30 mL) and stirred vigorously at room temp in the presence of air for 5 hours. The slurry was filtered through a pad of Celite. The organic extract was separated, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was triturated with methanol (25 mL) and the resultant suspension stirred at room temperature overnight. The solid was filtered, washed with cold (0° C.) methanol, and dried under vacuum to provide methyl 5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy[1,6]-naphthyridine-7-carboxylate as light brown solid.

Provenance & Evidence