1-Hydroxybenzotriazole → N-[6-(3-Hydroxyazetidin-1-yl)pyridin-3-yl]-6-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide

Participants

Reaction Steps

114 mg (0.59 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and 81 mg (0.59 mmol) of 1-hydroxybenzotriazole (HOBT) are added to a solution, stirred at 20° C. under an inert atmosphere, of 0.2 g (0.59 mmol) of 6-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared in stage 1.4, in 5 ml of DMF. The reaction mixture is stirred at ambient temperature for 15 minutes. 145 mg (0.88 mmol) of 3-amino-6-(3-hydroxyazetidin-1-yl)pyridine, prepared in stage 2.2, are subsequently added to the reaction mixture. After stirring at 20° C. for 20 hours, the reaction mixture is poured into a mixture of 30 ml of a saturated aqueous solution of NaHCO3 and 30 ml of ethyl acetate. The resulting mixture is separated by settling out and the aqueous phase is extracted with 20 ml of ethyl acetate. The combined organic phases are washed three times with 30 ml of water, dried over sodium sulphate and then concentrated under reduced pressure. The product obtained is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol. The solid obtained after evaporation of the solvent under reduced pressure is recrystallized from isopropyl ether. 175 mg of the expected product are thus isolated.

Provenance & Evidence