Abstract
An efficient hydrogenation protocol under continuous flow conditions was developed for the synthesis of underrepresented semi-saturated bicyclic fragments containing highly sp 3-rich skeletons for fragment-based drug discovery (FBDD) programs. Excellent yields were generally achieved by using Pd/C (10 % w/w) and RaNi at 25–150 °C under 4–100 bar of hydrogen pressure. The generated fragments, with appropriate physicochemical properties, present diverse hydrogen-bonding pharmacophores and useful vectors for their synthetic elaboration in the optimization stage. Successive, simple functionalizations in continuous flow were accomplished to demonstrate the opportunity to develop multi-step continuous flow synthesis of valuable starting points for FBDD campaigns. A conclusive quality control (QC) was essential to discard those structures which do not fit the typical fragment library parameters.
Original language | English |
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Pages (from-to) | 1341-1349 |
Number of pages | 9 |
Journal | European Journal of Organic Chemistry |
Volume | 2019 |
Issue number | 6 |
Early online date | 7 Jan 2019 |
DOIs | |
Publication status | Published - 14 Feb 2019 |
Keywords
- Drug discovery
- Flow reactions
- Fused-ring systems
- Heterocycles
- Hydrogenation
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry