Antiinflammatory indomethacin di:alkylamino-ethyl ester derivs. - prepd. by heating indomethacin with an O-di:alkyl:aminoethyl-N,N'-di:isopropyl isourea in benzene

摘要

Indomethacin dialkylaminoethyl esters (I) and their hydrochlorides are new. In (I), R is methyl, ethyl or a higher homologue. (I) have antiinflammatory properties and can be used for the treatment of inflammatory (esp. rheumatic) diseases. Dimethylaminoethanol (18 g), diisopropyl-carbodiimide (26 g) and CuCl (0.1 g) are stirred 2 days at room temp., initial exothermic reaction causes the temp. to rise to 60 deg. Distn. of the reaction mixt. under reduced pressure gives N,N'-diisopropyl- 0-(2-dimethyl aminoethyl) isourea (IIIa) (32.0 g), b.pt. 92 deg/6 mm. (IIIa) (4.4 g) and indomethacin (7.2 g) in benzene (100 ml) are refluxed 22 hrs., cooled to room temp., filtered from pptd. diisopropylurea (2.4 g), washed with ice-cold IN NaOH and evaporated. The residual oil is digested with petroleum ether to give crystalline (I; R:CH3) (8.0 g) as colourless crystals, m.pt. 84 deg.