Isoindoline → N-[4-(3-Piperidin-1-ylpropoxy)-2-trifluoromethyl-benzoyl]isoindoline hydrochloride

A solution of 4-(3-piperidin-1-yl-propoxy)-2-trifluoromethyl-benzoyl chloride (D6) (150 mg) in DCM (10 ml) was added to isoindoline (0.046 ml) and diethylaminomethyl polystyrene (0.60 g; 3.2 mmol/g). The mixture was stirred for 16 h, then loaded directly onto a silica column and eluted with 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM. The isolated free base was dissolved in DCM (5 ml) and treated with 4N HCl/dioxane solution (1 ml) with stirring for 10 min. The mixture was concentrated, and the residue co-evaporated with toluene (3×10 ml) and then dried at 50° C. under high vacuum for 16 h to yield the title compound (E16) as a beige solid (0.094 g). MS electrospray (+ion) 433 (MH+). 1H NMR δ (DMSO-d6): 9.96 (1H, s), 7.63 (1H, d, J=8.36 Hz), 7.46-7.23 (6H, m), 4.82 (2H, s), 4.47 (2H, s), 4.20 (2H, t, J=5.88 Hz), 3.47 (2H, m), 3.19 (2H, m), 2.87 (2H, m), 2.20 (2H, m), 1.80-1.38 (6H, m).