Ammonium Chloride → 2-(8-Fluoro-2-(3-formyl-4-iodopyridin-2-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile

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Reaction Steps

In a 100 mL round-bottomed flask 2-(8-fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile (800 mg, 3.47 mmol, 1 equiv.) was combined with THF (32.0 ml) to give a yellow suspension. A solution of lithium bis(trimethylsilyl)amide in THF 1M (4.52 ml, 4.52 mmol, 1.3 equiv.) was added. The reaction mixture was stirred at room temperature for 15 min. To the resultant amber solution was added 2-fluoro-4-iodonicotinaldehyde (1.31 g, 5.21 mmol, 1.5 equiv.). The reaction mixture was heated at 50° C. with stirring for 15 h. The reaction mixture was poured into 5 mL saturated NH4Cl and 100 mL H2O and extracted with DCM (3×100 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0%, then 0% to 0.5% MeOH in DCM), followed by trituration with ether:hexanes (1:8) to afford 2-[8-fluoro -2-(3-formyl-4-iodo-pyridin-2-yl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile as a pale yellow solid (830 mg). (M+H)+=462 m/e.

Provenance & Evidence