Preparation and application of 2-Boc-amino-3-pyridinecarboxaldehyde_Industrial additives

Background and Overview

2-Boc-amino-3-pyridinecarboxaldehyde can be used as a pharmaceutical synthesis intermediate. 2-aminopyridine can be used as the reaction raw material and reacted with (Boc)₂O protecting group to prepare intermediate 2- (tert-butoxycarbonylamino)pyridine, prepared by reacting with tert-butyllithium and DMF.

Preparation and application of 2-Boc-amino-3-pyridinecarboxaldehyde

Preparation and application of 2-Boc-amino-3-pyridinecarboxaldehyde Step 1: 2-(tert-butoxycarbonylamino)pyridine (9a)

To a solution of (Boc)₂O (218g, 1.0mol) in tert-butanol (1.5L), 2-aminopyridine (94g, 1.0mol) was slowly added, and the mixture was brought to room temperature. Stir for 24h, then concentrate under reduced pressure and purify by column chromatography (anhydrous calcium carbonate PE/EA=1/1) to obtain compound 9a, a white solid, yield 100g, 51%.

Preparation and application of 2-Boc-amino-3-pyridinecarboxaldehyde Step 2: 2-Boc-amino-3-pyridinecarboxaldehyde (9b)

To a solution of compound 9a (14.0 g, 72 mmol) in Et₂O (500 mL) at -78°C under an N₂ atmosphere was added tert-butyllithium (1.7M, 106mL, 180mmol), and the resulting mixture was warmed to 0°C and stirred for 1 hour. Anhydrous DMF (8.0mL, 103mmol) was added under rapid stirring. The mixture was stirred at 0°C for 10 minutes and then quenched with a semisaturated aqueous solution of NH4Cl. The aqueous layer was extracted twice with EA. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography. (PE/EA=3/1), compound 2-Boc-amino-3-pyridinecarbaldehyde was obtained as a white solid, yield 8.0g, 52%.

Preparation and application of 2-Boc-amino-3-pyridinecarboxaldehyde

2-Boc-amino-3-pyridinecarboxaldehyde can be used to prepare the compound 7-benzyl-6-(quinoline-8-sulfonyl)-6,7-dihydro-5H-imidazo[1,2- a]pyridyl[3,2-f][1,4]diazepine. The compound is a modulator for the orphan nuclear receptor RORy and can be used to treat RORy-mediated chronic inflammatory and autoimmune diseases by administering these novel RORy modulators to humans or mammals in need.

References

[1] From PCT Int. Appl., 2013064231, 10 May 2013