Some new NSAIDs prodrugs: An efficient synthesis, spectral characterization and X-ray crystal structure studies

Abstract

An efficient synthesis of some new NSAIDs prodrugs viz., (S)-ethyl 2-[(S)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (1), (S)-ethyl 2-[(R)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (2), (S)-dimethyl 2-[2-(2,3-dimethylphenylamino)benzamido]- succinate (3) and (RS)-methyl-2-(2-(2,6-dichloro-3-methylphenylamino)benzamido)butanoate (4) with high purity were carried out by the amidation of RS-ibuprofen, mefenamic acid and meclofenamic acid with methyl ester and ethyl ester of amino acids L-leucine, Laspartic acid and DL-2-aminobutyric acid. The products formed were confirmed by IR, 1H NMR, 13C NMR, HR MS (1-4) and single crystal X-ray crystallography analysis (2-4). Compound (2) crystallizes in orthorhombic space group P212121 with unit cell dimensions a = 5.1931 (2) Å, b = 10.0031 Å, c = 41.0764 (11) Å, α = β = γ = 90°, V = 2133.80 (12) Å3, Z = 4. Compound (3) crystallizes in hexagonal space group P65 with unit cell dimensions a = 11.4965 (3) Å, b = 11.4965 (3) Å, c = 26.5323 (12) Å, α = β = 90°, γ = 120°, V = 3036.94 (18) Å3, Z = 6. Compound (4) crystallizes in triclinic space group Pi with unit cell dimensions a = 8.7969 (3) Å, b = 10.6307 (3) Å, c = 11.8469 (4) Å, a = 76.724 (3)°, b = 89.066 (3)°, g = 66.169 (2)°, V = 982.70 (5) Å3, Z = 2.