Synthesis of Masked Vicinal Amino Aldehydes of Pyrrolizine and Pyrrolo [1,2-c]thiazole Series

Abstract

Acylation of (1,3-dihydro-1,3-dimethyl-2 H-benzimidazol-2-ylidene)acetonitrilewith mixed anhydrides of N-Boc proline and4-thiazolidinecarboxylic acid was found to proceed at the exocycliccarbon atom yielding the corresponding C-acylderivatives. Removal of the protecting group with equimolar amountof hydrochloric acid effected simultaneous cyclization affording2-(3-amino-5,6,7,7a-tetrahydro-1-oxo-1 H-pyrrolizin-2-yl)-and 2-(5-amino-7,7a-dihydro-7-oxo-1 H,3 H-pyrrolo[1,2- C]thiazol-6-yl)-1,3-dimeth-ylbenzimidazoliumchlorides. Reduction of the prepared salts with sodium borohydrideresulted in 3-amino-2-(2,3-dihydro-1,3-di-methyl-1 H-benzimidazol-2-yl)-5,6,7,7a-tetrahydro-1 H-pyrrolizin-1-one and 5-amino-6-(2,3-dihydro-1,3-dimethyl-1 H-benzimidazol-2-yl)-1,7a-dihydro-3 H,7 H-pyrrolo[1,2- C]thiazol-7-one, respectively. Thesecompounds were shown to be masked aldehydes. Their reactions withphenylhydrazine and hydroxylamine yielded corresponding hydrazonesand oximes, whereas condensation with malononitrile furnished 2-amino-5a,6,7,8-tetrahydro-5-oxo-5 H-pyrido[3,2- B]pyrrolizine-3-carbonitrileand 2-amino-5a,6-dihydro-5 H,8 H-thiazolo[3′,4′:1,5]pyrrolo[2,3- B]pyridine-3-carbonitrile.