Propiolic Acid → 6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole

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A solution of propiolic acid (0.52 g.) in anhydrous methylene chloride (10 cc.) is added to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (3 g.) and N,N'-dicyclohexylcarbodiimide (1.52 g.) in anhydrous methylene chloride (70 cc.). The mixture is stirred for one and a half hours at a temperature of about 25° C. and then the insoluble product (dicyclohexylurea) is filtered off and washed with methylene chloride (3×5 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue is treated with boiling ethanol (100 cc.). After cooling, the insoluble product is filtered off and washed with ethanol (20 cc.). This product is then dissolved in methylene chloride (200 cc.) and the solution is washed by decantation successively with 0.1 N methanesulphonic acid (50 cc.) and with water (2×50 cc.). After drying, the organic solution is filtered through silica gel (45 g.) contained in a column of diameter 2.2 cm. Elution is carried out using pure methylene chloride (1,000 cc.). The eluate is discarded. Elution is then carried out using a mixture of methylene chloride and methanol (99.5-0.5 by volume; 350 cc.) and the corresponding eluate is concentrated to dryness under reduced pressure (20 mm. Hg). The residue obtained is dissolved in a mixture of methylene chloride and methanol (90-10 by volume; 300 cc.) and the solution obtained is filtered and then concentrated to dryness under reduced pressure. 6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (0.8 g.), which melts at 302° C. with decomposition, is thus obtained.

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