Rapid catalyst identification for the synthesis of the pyrimidinone core of 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.
Department of Chemistry, University of Pennsylvania, Philadelphia, 19104-6323, USA.
Ana
A
Bellomo
Nihan
N
Celebi-Olcum
Xiaodong
X
Bu
Nelo
N
Rivera
Rebecca T
RT
Ruck
Christopher J
CJ
Welch
Kendall N
KN
Houk
Spencer D
SD
Dreher
D002384:Catalysis; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000378:metabolism*; D013329:Structure-Activity Relationship
D019428:HIV Integrase Inhibitors; D011744:Pyrimidinones; D019427:HIV Integrase