8-Oxa-3-aza-bicyclo(3.2.1)octane hydrochloride → (2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)propan-2-ol

Participants

Reaction Steps

A solution of 7-methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (Intermediate F, 0.195 g, 0.68 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (0.506 g, 3.38 mmol, 10 equiv.) in DMF (4.5 mL) was heated in a microwave reactor for 45 min. at 140° C. The resulting mixture was concentrated under reduced pressure. The residue was treated with a 4:1 CH2Cl2/isopropanol solution (25 mL), washed with a saturated sodium bicarbonate solution (25 mL), dried (anh. sodium sulfate) and concentrated under reduced pressure. The resulting residue was purified using MPLC to give N-(8-{[(2R)-2-hydroxy-3-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-ylamine (0.74 g, 16%): HPLC ret. time 0.70 min.; mass spectrum m/z 402 ((M+1)+, 7%).

Provenance & Evidence