Triethylamine → racemic 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[1-(2-pyridinyl)ethyl]-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline

Participants

Reaction Steps

To a solution of 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine (for a preparation see Intermediate 64, 380 mg) in DCM (20 ml) was added tetrahydro-2H-pyran-4-carboxylic acid (240 mg) followed by HATU (1.2 equiv) and triethylamine (1.5 equiv). The reaction mixture was stirred at room temperature for 1 h, and then hydrolysed using a saturated solution of sodium hydrogen carbonate. The mixture was extracted with DCM and the organic was dried over Na2SO4, filtered and concentrated to dryness. The resulting crude product was diluted in acetic acid (5 ml) and heated at 100° C. overnight. The reaction mixture was then taken-up in a 1:1 mixture of sodium hydroxide (1N) and water (total 100 ml), extracted with DCM and the resulting crude product was purified by chromatography on silica gel eluting with DCM/methanol (95:5). The resulting product was taken-up in diethyl ether and dried under vacuum to give racemic 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[1-(2-pyridinyl)ethyl]-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline (400 mg) as a grey powder.

Provenance & Evidence