5-Fluoro-2,3-dihydro-1H-isoindole → N-{4-[(1-Cyclobutyl-4-piperidinyl)oxy]benzoyl}-5-fluoro-isoindoline hydrochloride

Participants

Reaction Steps

A stirred mixture of 4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride (D25) (0.20 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 0.80 g) in DCM (10 ml) at rt was treated with 5-fluoroisoindoline (0.101 g) and stirred for 16 h. The reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)]. Fractions containing the required product were evaporated, redissolved in DCM, treated with excess hydrogen chloride (1 M solution in diethyl ether) and then concentrated. The residue was crystallised from acetone to yield the title compound (E60) as a white powder (150 mg). MS electrospray (+ion) 395 (MH+). 1H NMR δ (DMSO-d6): 10.60 (1H, s), 7.62 (2H, m), 7.42-7.06 (5H, m), 4.85 (4H, m), 4.66 (1H, m), 3.75-3.55 (1H, m), 3.45-3.20 (2H, m), 2.90 (2H, m), 2.41-1.62 (10H, m).

Provenance & Evidence