Acetyl chloride → N-(6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1,3-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)acetamide

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Reaction Steps

To the product of EXAMPLE 40 (72 mg) in THF (3 mL) and DMF (0.2 mL) was added NaH (10 mg, 60% dispersion in mineral oil) followed by acetyl chloride (30 μL). After stirring 30 minutes at room temperature NEt3 (45 μL) was added. After an additional hour of reaction time TLC indicated incomplete reaction. Acetyl chloride (15 μL) and NEt3 (45 μL) was added to the reaction, however this generated the imide (N-acetyl-N-(7-(2,4-dichlorophenyl)-6-(4-chlorophenyl)-1,2-dihydro-1,3 dimethyl-2-oxo-1,8-naphthyridinyl)acetamide). The reaction was quenched with methanol and NaHCO3, diluted with EtOAc and washed with 2 M aqueous HCl followed by 1 M aqueous NaOH solution. The solution was concentrated and the residue in 8 mL of 2:1 THF:methanol was treated with CS2O3 (80 mg). TLC indicated conversion of the imide to the amide after about 10 minutes at room temperature. The reaction was concentrated, dissolved in EtOAc and washed with brine. The concentrated solution was then purified by flash chromatography (silica gel) gradient eluted with 0-90% EtOAc in hexane affording the title compound. HPLC/MS: 486.0 (M+1), 488.0 (M+3); Rt=4.24 min.

Provenance & Evidence