Triethylamine → 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

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Reaction Steps

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (200 mg, 0.48 mmol), 3(R)-methyl-1-benzoylpiperazine hydrochloride (130 mg, 0.58 mmol) and triethylamine (0.20 mL) in DMF (3 mL) was added HATU (220 mg, 0.58 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (˜5 mL) stirred for 30 min, and the solids (290 mg) collected by filtration and flushed with H2O. The crude solids were dissolved into MeOH/THF (1:1, 4 mL) and treated with 1M aqueous NaOH (0.75 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (5 mL), neutralized with 1M aqueous HCl (0.75 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O and dried under vacuum to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 6-[[(2R)-4-benzoyl-2-methyl-1-piperazinyl]carbonyl]-13-cyclohexyl (257 mg, 0.44 mol, 90%). LCMS: m/e 586 (M−H)−, ret time 1.48 min, column A, 2 minute gradient.

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