Synthesis of 5- 2-Aminoacetyl pyrroles

Treatment of polymer-bound 5-(2-bromoacetyl)pyrroles with secondary amines in DMF at room temperature provided 5-(2-aminoacetyl)pyrroles which were cleaved from the resin with 20% TFA/CH2C12 (Fig. 6.15). FIPLC-purities of the crude products ranged from 74% to 92%. 

When these reaction conditions were applied to thioureas as heterocyclization components, the purities of the resulting aminothiazolylpyrroles were poor. However, this drawback was overcome by changing to DMF/AcOH 95 5 as solvent (Fig. 6.16b, d). The variation of amines and thioureas provided crude products with HPLC-purities of 50% to 92 %, the majority having purities 80 %. 

The reaction of polymer-bound 5-(2-bromoacetyl)pyrroles with selenourea in DMF led to selenazolylpyrroles (Fig. 6.16c, d) with HPLC-purities ranging from 0% to 85%. No product was obtained when 3-amino-l-propanol was used as the amino component purities in all other cases were 70 %. 

Treatment of polymer-bound 5-(2-bromoacetyl)pyrroles with 2-aminopyridines or 2-aminopyrimidines resulted in the formation of imidazo[l,2-a]pyridylpyrroles or imida-zo[l,2-a]pyrimidylpyrroles respectively. Optimal reaction conditions for this heterocyclization were 7 h at 60 °C in DMF/EtOH (1 1) (Fig. 6.17). 

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