Preparation and application of 2,3,6-trifluoropyridine_Industrial additives

Background and overview of preparation and application of 2,3,6-trifluoropyridine

2,3,6-Trifluoropyridine is a chemical substance that is a transparent, polycarbonate-free liquid. 2,3,6-Trifluoropyridine can be obtained from 2,3,5,6-tetrafluoropyridine by removing one fluorine. There are reports in the literature that 2,3,6-trifluoropyridine can be used to prepare small molecule inhibitors of MALT1.

Preparation and application of 2,3,6-trifluoropyridine

Dissolve BDIAlH2 (29mg, 0.081mmol, 1 equivalent) in C6H6 (0.3mL) and [Cp*RhCl (μ-Cl)]₂ (1) (1mg, 0.0016mmol, 0.02 Equivalent), suspend it in C6H6 (0.2mL), combine the mixture to obtain a light brown solution, add it to 2,3,5,6-tetrafluoropyridine (0.081mmol, 1 equivalent), and add α, α, α-Trifluorotoluene (10.1 μL, 0.081 mmol, 1 equivalent) was used as an internal standard. The resulting solution was transferred to a J-Young NMR tube equipped with a C6D6 capillary and sealed with a Teflon cap. The NMR spectrum was measured to determine the fluoroarene the initial concentration. Heat the NMR tube at 100 °C, quench the reaction by adding MeOH (0.05 mL) to the NMR tube, and heat at 100 °C for 2 h to obtain the product 2,3,6-trifluoropyridine (29%), area Selectivity: >99%, chemical selectivity: 89.4%, TON: 9.1, TOF: 2.3-1, yield: 32.5%.

Preparation and application of 2,3,6-trifluoropyridine

2,3,6-Trifluoropyridine can be used as a pharmaceutical intermediate for the synthesis of the following pyrazole derivatives. This type of compound is a small molecule inhibitor of MALT1. MALT1 is a paracaspase-like enzyme related to proteases of the caspase (cysteine-aspartic acid protease) family, but it follows an arginine or lysine residue instead of Cleavage occurs after aspartate (Rebeaud et al., 2008). MALT1-deficient animals display defects in B and T cell function but are otherwise healthy (Ruefli-Brasse et al., 2003; Ruland et al., 2003), and MALT1 is the only paracaspase in the human genome. These factors suggest that MALT1-targeted therapy will likely be well tolerated and have few or manageable toxicities. Therefore, MALT1 represents a potentially important therapeutic target for ABC-DLBCL and MALT lymphoma.

References

[1] Ekkert O, Strudley S D A, Rozenfeld A, et al. Rhodium Catalyzed, Carbon–Hydrogen Bond Directed Hydrodefluorination of Fluoroarenes[J]. Organometallics, 2methoxypyridine014, 33(24):7027-7030 .

[2] From U.S. Pat. Appl. Publ., 20190381019, 19 Dec 2019