Lithium Hexamethyldisilazide → 5-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide

Participants

Reaction Conditions

Reaction Steps

To a mechanically stirred solution of 5-(2-fluoro-4-iodophenylamino)imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester (82.17 g, 0.2 mol) and O-(2-vinyloxyethyl)hydroxylamine (40.73 g, 0.382 mol) in dry THF (1.27 L) at 5° C. under N2 atmosphere, was added lithium bis(trimethylsilyl)amide as a solution in THF (1 L, 1 M, 1 mol) over 1 hr, maintaining the temperature below 110° C. The reaction mixture was stirred at 0-5° C. for 20 minutes before being quenched with addition water (200 ml) and saturated saline (350 mL). Volatile solvents were removed in vacuo and the residue diluted with water (1.5 L) and extracted 2-methyl tetrahydrofuran (3×1 L). The organic layers were washed water (500 mL), saturated saline (500 mL), dried (Na2CO3) and absorbed onto silica gel (200 g) and purified on silica gel (400 g) using ethyl acetate as eluent. The resultant crude product was triturated with tert-butyl methyl ether (400 mL) to yield the title compound as a brown solid (58.36 g, 60%). LCMS (Method B): RT=2.79 min, [M+H]+=483.

Provenance & Evidence