After identifying a novel reaction, the time consuming and often tedious process of reaction optimization begins, followed by substrate screening. While microscale reactions can be performed in parallel using a heating block, some reaction parameters cannot be adjusted easily in this format, consuming precious time for manually performed, sequential reactions. To overcome this process the CEM Explorer auto-sampler was developed, allowing researchers a more efficient way to survey and improve their chemistry. Varied 1,4-dihydropydirines were synthesized in moderate to good yields in a “hands-free” fashion, using the Explorer autosampler to run this small library of compounds in under an hour.