Preparation of 3-nitropyridine-2-carbaldehyde_Industrial additives

Preparation background and overview of 3-nitropyridine-2-carbaldehyde

3-Nitropyridine-2-carbaldehyde, also called 2-formyl-3-nitropyridine, is a pharmaceutical intermediate that can be used to prepare 2-methyl-3 from 2-chloro-3-nitropyridine. – Nitropyridine, obtained by oxidation of methyl group. 3-Nitropyridine-2-carbaldehyde can be used to prepare a pyrro[2,3-c]pyridine derivative such as 1-allyl-2,3-dimethyl-1H-pyrrolo[2,3- c] Pyridine-7-aldehyde, this type of compound has excellent proton pump inhibition and the ability to achieve reversible proton pump inhibition.

Preparation of 3-nitropyridine-2-carbaldehyde

Preparation step 1 of 3-nitropyridine-2-carbaldehyde, 2-methyl-3-nitropyridine di-n-butyl carbonate

Place 2-chloro-3-nitropyridine (20g, 0.126mol), methylboronic acid (8.3g, 0.139mol), tetrakis(triphenylphosphine)palladium(0) (14.58g, 0.013mol) and A solution of potassium carbonate (52.3 g, 0.378 mol) in anhydrous 1,4-dioxane (100 ml) was refluxed for 2 days. The reaction mixture was cooled to room temperature, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=1/3, v/v) to obtain 14 g of the title compound as a brown oil. ¹H-NMR (MHz, CDCl₃) δ8.74 (d, 1H), 8.27 (d, 1H), 7.34 (t, 1H), 2.88 (s ,3H)

Preparation step 2 of 3-nitropyridine-2-carbaldehyde, 2-formyl-3-nitropyridine

Add 2-methyl-3-nitropyridine (10.155g, 72.46mmol) and selenium dioxide (8.84g, 79.71mmol) prepared in step 1 in 1,4-dioxane (80ml) The solution was refluxed for 2 days. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=1/2, v/v) to obtain 12.8 g of the title compound as a red oil. ¹H-NMR (MHz rubidium tetrafluoroborate, CDCl₃) δ10.27 (s, 1H), 9.00 (d, 1H), 8.28 (t, 1H) ,7.76(d,1H)

References

[1] [Invented in China, authorized by China] CN200580029391.9 Pyrro[2,3-c]pyridine derivatives and preparation method thereof