Diisopropylethylamine → 4-Cyclobutylmethoxy-1H-indole-2-carboxylic acid {4-hydroxy-4-[2-((3S,4S)-4-hydroxy-3-methyl-piperidin-1-yl)-ethyl]-cyclohexyl}-amide

Participants

Reaction Steps

A solution of 4-cyclobutylmethoxy-1H-indole-2-carboxylic acid (16a) (140 mg, 0.383 mmol), (3S,4S)-1-[2-(4-amino-1-hydroxy-cyclohexyl)-ethyl]-3-methyl-piperidin-4-ol (14) (103 mg, 0.421 mmol) and DIEA (0.263 ml, 1.532 mmol) in 5 ml of DMF is treated with solid TBTU (139 mg, 0.421 mmol). The mixture is stirred for 2 h at rt and then evaporated. The crude residue is dissolved in EtOAc and extracted with 1M-HCl. The aqueous layer is separated, its pH adjusted to 14 and extracted 3-times with DCM. The organic layers are dried over sodium sulphate and evaporated. The crude product is then purified by chromatography on silicagel using methanol and DCM (saturated with ammonia) from 1:99 to 5:95.

Provenance & Evidence