Dichloromethane → HCID 69490986, compound

Participants

Reaction Steps

4-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester was prepared following the method in Example 10 using 3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester (E. J. Jacobsen et al; J. Med. Chem. 42, 1123-1144, 1999) instead of 2,3,5,6-tetramethylpiperazine. To an ice cooled solution of 4-{[1-(cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester (0.52 g, 1.08 mmol) in dichloromethane (5 ml) was added dropwise trifluoroacetic acid (2 ml). The mixture was allowed to warm to room temperature over 2 h before removal of any volatile components under reduced pressure. The residue was then suspended in 5 M sodium hydroxide solution (10 ml) and extracted into dichloromethane (2×30 ml). The combined organic layers were dried with magnesium sulfate and evaporated to an oil. This was purified by flash chromatography eluting with 5-10% (v/v) methanol in dichloromethane to afford the title compound (free base) as a colourless oil. The free base was dissolved in diethyl ether (3 ml) and treated dropwise with 2 M hydrochloric acid in diethyl ether (1 ml). The resulting precipitate was collected by filtration, washed with diethyl ether (15 ml) and dried under reduced pressure to afford the title compound (1:1 hydrochloric acid salt) as a colourless solid (0.13 g, 0.31 mmol). 1H NMR (400 MHz, CD3OD) δH 1.04 (2H, brq, J 9.0), 1.11-1.25 (3H, m), 1.44 (6H, d, J 7.0), 1.54 (2H, br d, J 13.0), 1.62-1.90 (4H, m), 3.33-3.42 (4H, m), 3.95 (3H, s), 4.26 (2H, d, J 7.0), 4.74-4.86 (2H, m), 6.76 (1H, d, J 7.5), 7.09 (1H, t, J 8.0), 7.21 (1H, d, J 7.5), 7.46 (1H, s); EIMS: m/z 384.2 [M+H]+.

Provenance & Evidence