N-bromobutanimide → Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate

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Reaction Steps

For example, 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid methyl ester 1A.4 (WO 0230930 A2, p. 171) is reacted with one molar equivalent of N-bromosuccinimide in dichloromethane, to yield 5-bromo-8-hydroxy-[1,6]naphthyridine-7-carboxylic acid methyl ester, 1A.5. The phenol is then reacted with p-toluenesulfonyl chloride and triethylamine in chloroform, for example as described in WO 02 30931 A2 p. 72, to give 5-bromo-8-(toluene-4-sulfonyloxy)-[1,6]naphthyridine-7-carboxylic acid methyl ester 1A.6. The product is then reacted with [1,2]thiazinane 1,1-dioxide 1A.7 and cuprous oxide in pyridine at reflux, for example as described in WO 0230931 A2, p. 73, to produce 5-(1,1-dioxo-1,2]thiazinan-2-yl)-8-(toluene-4-sulfonyloxy)-[1,6]naphthyridine-7-carboxylic acid methyl ester 1A.8. Deprotection, for example by reaction with methanolic sodium methoxide in dimethylformamide, as described in WO 0230931 A2 p. 74, then affords the phenol 1A.9.

Provenance & Evidence