Phosphorus oxychloride → 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinoline

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Reaction Steps

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (for a preparation see Intermediate 11) (0.33 g, 0.796 mmol) was heated in a mixture of POCl3 (1 ml, 10.73 mmol) and PCl5 (0.166 g, 0.796 mmol) at 120° C. for 5 h, then cooled and allowed to stand at room temperature overnight. The mixture was evaporated in vacuo and then the residue suspended in toluene and evaporated to a brown gum. This was dissolved in DCM (20 ml) and washed with saturated sodium hydrogen carbonate solution, then the organic layer was loaded onto a 25 g silica cartridge. The column was eluted with EtOAc/cyclohexane (0-100%) and the product-containing fractions evaporated in vacuo to give 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinoline (31 mg, 0.072 mmol, 8.99% yield) as a beige glass. LCMS (formate) Rt 1.05 min, MH+ 433.

Provenance & Evidence