Diethyl (ethoxymethylene)malonate → diethyl N-(1-phenyl-pyrazol-3-yl)-aminomethylenemalonate

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Reaction Steps

1-phenyl-3-amino-pyrazole, m.p. 90°-91° C. (18 g) was reacted with diethyl ethoxymethylenemalonate (29.3 g) in anhydrous ethanol (180 ml) at the reflux temperature for 15 hours. After cooling the solution was evaporated in vacuo to dryness: the residue was dissolved in isopropyl ether (200 ml) and decolorized by charcoal. Crystallization obtained by dilution with hexane gave diethyl N-(1-phenyl-pyrazol-3-yl)-aminomethylenemalonate, m.p. 81°-82° C. (31 g), which was reacted with polyphosphoric acid (13 g; 6.1 g of P2O5 and 6.9 g of H3PO4) and POCl3 (57 g) under stirring at the reflux temperature for 30 minutes. After cooling the reaction mixture was diluted with ice water and then the solution was decolorized, with charcoal: neutralization with 35% NaOH gave a precipitate which was filtered and washed with water. Washing with hexane gave 1-phenyl-7-oxo-1H,7H-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid, ethyl ester, m.p. 187°-190° C. (24.2 g), which was hydrolized by heating with a mixture 1:1 of 37% HCl:acetic acid (1.2 l) at the reflux temperature for 4 hours. After cooling the reaction mixture was neutralized to pH=6 with 35% NaOH and the precipitate was filtered and washed with water: crystallization from isopropyl alcohol gave 9.7 g of 1-phenyl-7-oxo-1H,7H-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid m.p. 185°-190° C. dec., N.M.R. (DMSO-d6) δ p.p.m.: 6.94 (d) (1H, C-3 proton), 7.59 (s) (5H, phenyl protons), 8.74 (d) (1H, C-2 proton), 8.81 (s) (C-5 proton).

Provenance & Evidence