Rapid Catalyst Identification for the Synthesis of the Pyrimidinone Core of HIV Integrase Inhibitors

• DOI: 10.1002/anie.201201720
• Publication Date: 2012-06-11T13:18:16Z
• Authors: Ana Bellomo; Nihan Celebi‐Olcum; Xiaodong Bu; Nelo Rivera; Rebecca T. Ruck; Christopher J. Welch; Kendall N. Houk; Spencer D. Dreher
• Keywords: Molecular Structure; HIV Integrase; Pyrimidinones; 01 natural sciences; Catalysis; High-Throughput Screening Assays; 0104 chemical sciences; Structure-Activity Relationship; Humans; HIV Integrase Inhibitors

A microscale chemistry improvement engine: a pre-dosed microscale high-throughput experimentation additives platform enables rapid, serendipitous reaction improvement. This platform allowed one chemist to set up 475 experiments and analyze the results using MISER chromatography in a single day, thus resulting in two high-quality catalytic systems for the construction of the title compound 1. Support for a single-electron transfer mechanism was obtained.