反应详情

A stirred mixture of 2-chloro-4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride (D36) (0.20 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 0.8 g) in DCM (10 ml) at rt was treated with 5-fluoroisoindoline hydrochloride (D8) (0.10 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 (1M solution in diethyl ether) and then concentrated. The residue was crystallised from acetone to yield the title compound (E65) as a white solid (0.14 g). MS electrospray (+ion) 430/432 (MH+). 1H NMR δ (DMSO-d6): 10.48 (1H, s), 7.46-7.06 (6H, m), 4.88-4.60 (3H, m), 4.51 (2H, m), 3.80-3.55 (1H, m), 3.46-3.18 (2H, m), 2.88 (2H, m), 2.38-1.64 (10H, m).

1. customThe reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]
2. additionFractions containing the required product
3. customwere evaporated
4. dissolutionredissolved in DCM
5. additiontreated with excess hydrogen chloride (1M solution in diethyl ether)
6. concentrationconcentrated
7. customThe residue was crystallised from acetone