7-Cyano-1,2,3,4-tetrahydroisoquinoline → N-[4-(3-Piperidin-1-ylpropoxy)benzoyl]-7-cyano-1,2,3,4-tetrahydroisoquinoline hydrochloride

Participants

Reaction Steps

A solution of 4-(3-piperidin-1-ylpropoxy)benzoyl chloride hydrochloride (D3) (0.14 g) in DCM (10 ml) was added to 7-cyano-1,2,3,4-tetrahydroisoquinoline (WO98/50364) (0.08 g) and diethylaminomethyl polystyrene (0.6 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) then crystallised from ethanol/diethyl ether, and dried at 80° C. under high vacuum for 16 h to yield the title compound (E18) as a beige solid (0.03 g). MS electrospray (+ion) 404 (MH+). 1H NMR δ (DMSO-d6): 9.91 (1H, s), 7.85 (1H, m), 7.65 (1H, d, J=7.9 Hz), 7.42 (3H, m), 7.02 (2H, d, J=8.6), 4.73 (2H, s), 4.11 (2H, t, J=5.9 Hz), 3.68 (2H, m), 3.44 (2H, m), 3.17 (2H, m), 2.93 (4H, m), 2.20 (2H, m), 1.91-1.41 (6H, m).

Provenance & Evidence