AEW1 is a derivative compound of chalcone proven to has an anti-inflammatory and antioxidant effect. The compound been synthesized by reacting 2,5-dihydroxyacetophenone and pyridine-2-carbaldehide in basic environment (K2CO3) using 4 minutes microwave radiation obtaining 54% yield. The study objectives were to obtain optimum synthesis condition during synthesize of AEW1 compound and to generate equation to calculate estimated theoretical yield if catalyst mass, microwave power and time reaction used were known. The study was done with variations of 0 - 3 mmol K2CO3 catalyst mass, 0–420 watt microwave power and 2 – 8 minutes of time reaction. Data obtained from those factors were analyzed with Response Surface Methodology (RSM). The obtained study results were optimum condition to synthesize AEW1 was 0,5 mmol catalyst of K2CO3, 165 watt microwave power and 3 minutes 36 seconds of time reaction. Theoretical yield result obtained was 16.0773% and experimental yield result was 15.8304%. The difference of yield obtained was 1.53%. The results showed < 5% AQL yield differences obtained. Hence, the equation obtained from optimization using RSM can be used to calculate theoretical yield of the compound.