Facile synthesis of 1-substituted 2-amino-3-cyanopyrroles: new synthetic precursors for 5,6-unsubstituted pyrrolo[2,3-d]pyrimidines.
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).
Chien
Tun-Cheng
TC
Department of Chemistry, College of Literature, Science and Arts, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Meade
Eric A
EA
Hinkley
Jack M
JM
Townsend
Leroy B
LB
D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
D002219:Carbamates; D011743:Pyrimidines; D011758:Pyrroles