A solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide (108 mg) [see Example 8] and 37% aqueous formaldehyde (0.21 ml) in acetonitrile (3 ml) was added to sodium cyanoborohydride (86.5 mg), followed by glacial acetic acid (0.1 ml). The reaction mixture was stirred at room temperature for 1.5 hours, after which time glacial acetic acid (0.1 ml) was added, and the mixture was stirred for a further 30 minutes. Diethyl ether was added to the mixture and the organic layer was washed several times with 2N aqueous sodium hydroxide solution. The organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 97:3.5:0.5 changing to 97:3:1, by volume, dichloromethane:methanol:0.88 aqueous ammonia solution, to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,4,6-trimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide (53.1 mg) as a white solid.
