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

Participants

Reaction Steps

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (470 mg, 1.13 mmol), tert-butyl piperazine-1-carboxylate (250 mg, 1.36 mmol) and triethylamine (0.30 mL) in DMF (5 mL) was added HATU (520 mg, 1.36 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (˜6 mL) and extracted with EtOAc (2×10 mL). The combined organics were washed with brine (10 mL), dried (MgSO4), filtered and concentrated. The residue was dissolved into MeOH//THF (1:1, 10 mL) and treated with 1M aqueous NaOH (1.4 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 30 min in a sealed tube, additional 1M aqueous NaOH (0.50 mL.) was added and the reaction was reheated at 80° C. for 15 min. The clear solution was diluted with H2O (10 mL), neutralized with 1M aqueous HCl (1.9 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O, dried under vacuum and purified by preparative HPLC (MeOH/H2O with NH4OAc buffer) to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-[(1,1-dimethylethoxy)carbonyl]-1-piperazinyl]carbonyl] (335 mg, 0.59 mmol, 43%) as a yellow solid. 1H NMR (500 MHz, CD3OD) δ 8.23 (s, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.75 (dd, J=8.5, 1.2 Hz, 1H), 7.65 (br d, J=6.4 Hz, 1H), 7.60-7.53 (m, 3H), 7.03 (s, 1H), 5.18 (br s, 1H), 4.43 (br s, 1H), 3.42-3.25 (m, 8H), 2.95-2.86 (m, 1H), 2.21-1.19 (m, 10H). LCMS: m/e 568 (M−H)−, ret time 1.36 min, column D, 2 minute gradient.

Provenance & Evidence