Benzamide → HCID 89928165, compound

Participants

Reaction Steps

With these cyclization conditions in hand, N-acyl amino imidazolin-2-one amide 14 was synthesized to study the conformation of this model system in the solid state and in solution, using X-ray crystallography and NMR spectroscopy, respectively (Scheme 2). Benzhydrylidene aza-glycinyl-D-phenylalanine isopropyl amide 9 was prepared from benzhydrylidene aza-glycinyl-D-phenylalanine tert-butyl ester 7 by tertbutyl ester cleavage in a 1:1 v/v mixture of TFA: DCM, followed by coupling to iso-propylamine using a mixed anhydride approach.xx Employment of amide 9 in the alkylation and cyclization steps minimized racemization, likely due to preferential amide nitrogen deprotonation inhibiting removal of the α-hydrogen. Indeed, in comparison to the alkylation of aza-glycinyl-D-phenylalanine tert-butyl ester 7, the chemoselective alkylation of semicarbazone 9 gave aza-propargyl glycinamide 10 in 71% yield with no detectable racemization (see above). Subsequent NaH-promoted 5-exo-dig cyclization gave imidazolin-2-one 11, possessing an exocyclic double bond, in a 57% yield. However, olefin migration occurred upon hydrazone removal, using hydroxylamine hydrochloride in pyridine 11 to afford N-amino imidazalone 12, which without further purification was treated with 4-methoxybenzoyl chloride to provide N-acyl dipeptide amide 14 in 56% yield.

Provenance & Evidence