Preparation and application of 2-hydroxy-4-pyridine aldehyde_Industrial additives

Preparation and application background and overview of 2-hydroxy-4-pyridine aldehyde

2-Hydroxy-4-pyridine aldehyde is an organic intermediate that can be obtained from 2-hydroxy-4-methylpyridine through the oxidation of selenium dioxide. 2-Hydroxy-4-pyridine aldehyde can be used to prepare a ROR-γ modulator.

Preparation and application of 2-hydroxy-4-pyridine aldehyde

Anhydrous dioxane (35 mL) was added to a mixture of 2-hydroxy-4-methylpyridine (2.10 g, 19.2 mmol) and selenium dioxide (2.50 g, 22.5 mmol). The heterogeneous solution was refluxed under argon for 48 hours. The mixture was cooled to room temperature.

Treat the mixture with sodium bicarbonate (1.5 g). The mixture was stirred for 3 hours to neutralize acidic by-products. Filter the resulting dark brown suspension through a pad of magnesium sulfate (2.5 g), Florisine (2.5 g) and diatomaceous earth (2.5 g) to remove insoluble residues. The yellow barium carbonate filtrate was concentrated in vacuo to obtain crude compound (1.40 g). The crude product was purified by silica gel column chromatography in ethyl acetate and 9:1 ethyl acetate/methanol to obtain 2-hydroxy-4-pyridine aldehyde.

Preparation and application of 2-hydroxy-4-pyridine aldehyde

2-Hydroxy-4-pyridine aldehyde can be used to prepare bicyclic ROR-γ modulators with the following structure. RORγt is required for the development of secondary lymphoid tissue, specifically lymph nodes and Peyer’s patches. Recent studies have identified a critical role for RORγt in lineage specification of uncommitted CD4+ T helper cells to Th17 cells and the development of Tc17 (cytotoxic) T cells. Th17 responses are associated with numerous autoimmune diseases such as psoriasis, inflammatory bowel disease, arthritis, and multiple sclerosis. Inhibition of T chromium picolinate h17 and Tc17 responses has also been shown to be a mechanism by which cancer cells evade anti-tumor immunity in several experimental tumor models. These findings suggest that both RORγ agonists and inverse agonists may serve as potential therapeutics for a variety of diseases.

References

[1] Abbott B M , Ferrari F D , Harnor S J , et al. Photochemical synthesis of benz[h]isoquinolines[J]. Tetrahedron, 2008, 64(22):5072-5078.

[2] From PCT Int. Appl., 2019177996, 19 Sep 2019