2,4,6-Trimethylpyridine → HCID 16073864, compound

Participants

Reaction Steps

Methanesulfonyl chloride (0.06 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (250 mg) from Preparation No. 10, DMAP (14.4 mg), and 2,4,6-collidine (0.11 mL) in anhydrous DMF (12 mL). The mixture is stirred at room temperature until the starting material is consumed. (1S, 4S)-(+)-2-Aza-5-oxabicyclo[2.2.1]heptane hydrochloride (475.9 mg) and Et3N (0.49 mL) are added to the solution. The reaction mixture is heated to 65° C. overnight. The mixture is cooled to room temperature and filtered to remove the salt that had precipitated out of solution. The filtrate is diluted with water (125 mL) to precipitate the product. The solid is adsorbed onto silica and purified by column chromatography (eluent 1% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (1 L), 3% MeOH in CH2Cl2 (2.5 L)). Fractions homogenous by TLC are combined, concentrated, and recrystallized from CH2Cl2/hexanes to afford 164.0 mg (53%) of the title compound as a white solid.

Provenance & Evidence