Amidine or Nitrile Derivatives

This approach was later extended to investigate a synthesis of 5-aminoimidazoles (96) by chemical transformations using the more readily 

R2 = CH2Ph) [74BSF(2) 1453]. The unexpected stability of the latter four examples was attributed by the authors to the presence of phenyl substituents (83JHC1015). 

Treatment of a methanolic solution of the nitrile derivative (116 R1 = CONHCH2CN) [prepared in two steps from the calcium antagonist compound (116 R1 = H)] with sodium hydride resulted in facile cyclization giving the 5-aminoimidazol-2-one derivative (117), which was isolated as the hydrochloride salt (29%) (90JMC1805). 

The instability of 5-aminoimidazoles (96) has led to in situ acylation being used to obtain stable compounds and using this approach several derivatives have been prepared. For example, a solution of the appropriate 5-nitroimidazole (97) in ethyl acetate was reduced with Raney nickel, and the resulting solution of 5-aminoimidazole (96) then treated with an acid chloride to give the amides (118 R1 = Me, R2 = S02Me, COPh, R3 = alkyl, aryl, hetaryl) (25-45%) [82IJC(B)1087], 

A slightly modified procedure facilitated the synthesis of the acetamide (118 R = Me, R2 = 3-methanesulfonyl-imidazolidin-2-on-l-yl, R3 = Me). Thus, a solution of the requisite 5-nitroimidazole (97 R = Me, R2 = 3-methanesulfonyl-imidazolidin-2-on-l-yl) in a mixture of dimethylform- 

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