Synthesis of a pyrazole library using purification by solid phase extraction

Synthesis of a pyrazole library using purification by solid phase extraction 

Another example of a multistep synthesis using only PSQ purification procedures was described by Hodges etal. In the first step, 1,3-diketone 47 was reacted with an excess of hydrazine 48 in the presence of morpholinomethyl-polystyrene (49). Removal of excess 48 by quenching with polymer-bound isocyanate 50 afforded pyrazole 51 with a purity of 97% (HPLC) but in quite moderate yield (48%). In the second step, 51 was converted into a mixed anhydride (by treatment with isobutyl chloroformate in the presence of 49) and subsequently transformed in situ into 5 3 by reaction with an amine. Addition of the polymer-bound reagents 50 and 52 removed excesses of chloroformate and amine by filtration and 53 was isolated in 75% yield with a purity of 97% (HPLC). 

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