Furo pyridine-5-carboxylates

Furo[2,3-b]pyridine-5-carboxylates (581) were obtained from 2-furyl-aminomethylenemalonates (580) by heating in Dowtherm A (66JHC202). 

A/-(Furo[3,2-i>]pyridin-2-yl)aminomethylenemalonates (1432) were stirred in a 1.2 N ethanolic solution of potassium hydroxide at ambient temperature for 1.5 hr, or in a 2 N ethanolic solution of sodium hydroxide under reflux for 6 hr, to give the 3-carboxylic acid (1433) in 33-61% yield (84G211). Solutions of N-(furopyridin-2-yI)aminomethylenemalonates (1432) in 2 N hydrochloric acid were refluxed for 2 hr to afford 2-aminofuro-pyridine-3-carboxylates (1434) in 55% and 82 % yields. When the 3-ethoxy-carbonyl derivative (1432, R = Et) was heated in a boiling aqueous ethanolic solution of potassium hydroxide for 2 hr, 2-pyridinylacetic acid (1435) was obtained in 47% yield. The treatment of the 4-nitrophenyl ester of 1432 (R = 4-N02Ph) with ethyl iodide in DMF in the presence of potassium carbonate gave the ethyl ester of 1432 (R = Et) in 91% yield (84G211). 

While the synthesis of benzofuran derivatives from suitable furan derivatives has been comparatively little investigated, the synthesis of fused two-ring and three-ring compounds containing a pyridine nucleus from furan derivatives has been more successful furo[3,2-c]pyridines (345),752>753 2,3-dihydrofuro[2,3-a ]quinolines (from 4,5-dihydro-3-furoic acid),754 acrophyllin (346), and 7-hydroxydictamnine (347) (from ethyl 2-ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylate),755 are examples of compounds in this class which have been prepared. 

In another synthesis using a preformed pyridine derivative a cyanoacetic acid ester is condensed in a Guareschi-type reaction with an a-substituted /3-keto carboxylic acid ester and an amine to give a hydroxypyridone (18 Scheme 3). These compounds are suitable precursors for an acid catalyzed cyclization to furo[2,3-6]pyridine-6-ones (19). N-Substituted derivatives may also be prepared by this route (64AP754). The aqueous solutions of these furopyridines show an intensive blue fluorescence. 

The construction of the furan ring in a Feist-Benary type reaction starting from 4-hydroxy-6-methylpyran-2-one (66) has also proved to be useful for the synthesis of furo[3,2-c]pyridines (Scheme 14) (75JHC461, cf. 71BSF4041). Quite recently the synthesis of the hitherto unknown furo[3,2-c]pyridin-3-ols has been described (79LA371). 4-Hydroxypyridine-3-carboxylates (e.g. 69), which are available from diketene and /3-aminocrotonic esters, react with a-halogenoketones in the presence of potassium carbonate to give compounds of type 70. 

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