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

Participants

Reaction Conditions

Reaction Steps

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (for a preparation see Intermediate 14) (220 mg, 0.539 mmol) was dissolved in POCl3 (2 ml, 21.46 mmol), PCl5 (0.2 g, 0.960 mmol) was added and the mixture was heated at 120° C. for 24 h. The reaction mixture was evaporated in vacuo to give a beige solid. This was dissolved in DCM (3 ml) and loaded onto a 25 g silica column, then eluted with 0-10% 2M methanolic ammonia/DCM (25 column volumes) and product containing fractions were evaporated in vacuo to give 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (14.2 mg, 0.033 mmol, 6.18% yield) as beige solid. LCMS (formate) Rt 0.81 min, MH+ 427.

Provenance & Evidence