Diethylcarbamoyl chloride → Diethyl-carbamic acid 5-diethylcarbamoyloxy-2-isopropyl-4-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-cyclohexa-1,3-dienyl ester

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Reaction Steps

To a solution of (2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone (1.0 g, 2.44 mmol) in THF (25 mL) containing Et3N (0.68 mL, 4.88 mmol) and N,N-4-dimethylaminopyridine (5 mg, 0.41 mmol) was added N,N-diethylcarbamoyl chloride (1.5 mL, 11.62 mmol). The solution was heated to 60° C. for 18 h when EtOAc (50 mL) and 10% aq K2CO3 (50 mL) were added. The organic phase was washed with saturated brine (30 mL) and the organic phase was separated and evaporated to a small volume. A solution of the residue in DCM was applied to a column containing silica gel and the product eluted successively with DCM followed by 0.2% aqueous ammonia in 5% MeOH in DCM. The fractions containing product were evaporated from DCM followed by diethyl ether to give the title compound as a foam 1.07 g. 1H NMR (400 MHz, DMSO-d6): 7.44 (1H, d), 7.37-7.30 (1H, m), 7.30-7.15 (2H, m), 7.01 (1H, s), 4.75 (2H, s), 4.61 (2H, d), 3.56-3.40 (4H, m), 3.33 (4H, d), 3.24 (3H, d), 3.19-3.09 (2H, m), 3.09-2.95 (2H, m), 2.85-2.56 (4H, m), 2.42 (3H, s), 1.38-0.76 (18H, m); m/z 608 (MH).

Provenance & Evidence