Facile synthesis of 1-substituted 2-amino-3-cyanopyrroles: new synthetic precursors for 5,6-unsubstituted pyrrolo[2,3-d]pyrimidines.

ABSTRACT

1-Benzyl-3-cyanopyrrole-2-carbonyl azide (5) underwent a Curtius rearrangement followed by quenching with alcohols to form the corresponding carbamates (6a-c). The carbamates 6a,b were unblocked to give the desired 2-amino-1-benzyl-3-cyanopyrrole (1a). A more facile procedure was subsequently developed for the synthesis of 1-substituted 2-amino-3-cyanopyrroles. N-Substituted aminoacetaldehyde dimethyl acetals (7a-c) were condensed with malononitrile in the presence of p-toluenesulfonic acid monohydrate to afford the corresponding 1-substituted 2-amino-3-cyanopyrroles (1a-c).