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

Abstract

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.

Synthesis of 2-(oxadiazolo, pyrimido, imidazolo, and benzimidazolo) substituted analogues of 1,4-benzodiazepin-5-carboxamides linked through a phenoxyl bridge

“…Established protocols on imidate derivative (9) was applied, employing the reagents ethylenediamine and o-phenylenediamine to form the dihydroimidazole (12) [whose oxidation with iodoxybenzoic acid provided imidazole (13)] and benzimidazole (14) bearing benzodiazepine nucleus, respectively (scheme 2). [27][28][29][30] All the synthesized compounds gave satisfactory results of their microanalysis, IR, 1 H NMR, 13 C NMR and MS spectral data which were found to be consistent to the assigned structures.…”

Automatic discovery and optimization of chemical processes

“…A significant departure from this approach is the use of dedicated robotic experimental systems, which could either involve parallel batch or flow experiments. Such systems are developed for high-throughput experiments and enable rapid discovery of new reactions [22,23,24 ], or optimization of process conditions of known reactions [25,26]. A flow array system has been used to discover a new inorganic cluster [7 ].…”

Optimization of 18F‐syntheses using 19F‐reagents at tracer‐level concentrations and liquid chromatography/tandem mass spectrometry analysis: Improved synthesis of [18F]MDL100907

“…There is increasing availability of LC‐MS/MS for other applications such as proteomics and metabolomics studies and clinical analysis . Labs who are routinely developing new radiochemistry will find it indispensable for the rapid analysis of parallel reaction optimization . Another advantage of the proposed approach is that no exposure to radioactivity is necessary as compared with the radioactive 18 F‐approach, as all reaction screenings are conducted with natural 19 F‐reagents.…”