Propanedioic acid, 2-(1-ethoxyethylidene)-, 1,3-diethyl ester → 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-carboxylic acid, ethyl ester

Participants

Reaction Steps

2-amino-5-morpholino-1,3,4-thiadiazole (5 g) was reacted with diethyl(1-ethoxy-ethylidene)-malonate (6.2 g) in diglyme (40 ml) at 150° C. for 20 hours. After cooling the reaction mixture was diluted with ice water and extracted with ethyl acetate; after evaporation in vacuo to dryness, the residue was purified over a SiO2 column using chloroform-methanol 98:2 as eluent. Crystallization from isopropyl ether gave 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-carboxylic acid, ethyl ester, m.p. 196°-198° C. (2.6 g), which was reacted with 2-amino-pyridine (2.25 g) in polyphosphoric acid (130 g) under stirring at 120° C. for 4 hours. After cooling, dilution with ice water and neutralization with 35% NaOH, the precipitate was filtered and washed with water to give 1.9 g of 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-N-(2-pyridyl)-carboxamide, m.p. 285°-287° C.

Provenance & Evidence