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. 2013 Nov 28;18(12):14747-59.
doi: 10.3390/molecules181214747.

OxymaPure/DIC: an efficient reagent for the synthesis of a novel series of 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives

Ayman El-Faham  1 , Zainab Al Marhoon, Ahmed Abdel-Megeed, Fernando Albericio
Affiliations

OxymaPure/DIC: an efficient reagent for the synthesis of a novel series of 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives

Ayman El-Faham et al. Molecules. .

Abstract

OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for use in the carbodiimide (DIC) approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity and yield. The title compounds were synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was reacted with 4-aminobenzoic acid under conventional heating as well as microwave irradiation to afford 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid. This α-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as a coupling reagent to afford 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives in excellent yield and purity. The synthesized compounds were characterized using FT-IR, NMR, and elemental analysis.

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Figures

Scheme 1
Scheme 1
General mechanism for the reaction of N-acylisatin (1) with amines.
Scheme 2
Scheme 2
Synthesis and reaction of N-acylisatin (1) with 4-aminobenzoic acid (2).
Scheme 3
Scheme 3
Synthesis 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives 4a–i.
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