Sodium Hydroxide → HCID 57559087, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 13-cyclohexyl-10-(((dimethylamino)sulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate (700 mg, 1.27 mmol) was dissolved into MeOH//THF (1:1, 14 mL) and treated with 1M aqueous NaOH (3 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min and cooled to rt. The clear solution was neutralized with 1M aqueous HCl (3 mL) and concentrated to remove organic solvents. The residue was stirred with H2O (10 mL) for 1 h and the resultant solids were collected by filtration, washed with H2O and dried under vacuum. To a solution of these solids, N1,N1,N2-trimethylethane-1,2-diamine (191 mg, 1.88 mmol) and triethylamine (0.700 mL) in DMF (5 mL) was added HATU (620 mg, 1.63 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (25 mL) and 1M HCl (aq.) (5 mL) and stirred 20 The precipitates were collected by filtration, rinsed with H2O and dried to yield impure 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (960 mg) as a yellow powder. A crude sample of 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (100 mg) was dissolved into MeOH/DMF (3:1, 4 mL), filtered and purified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer) to yield 13-cyclohexyl-N6-(2-(dimethylamino)ethyl)-N10-((dimethylamino)sulfonyl)-3-methoxy-N6-methyl-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxamide (78 mg, 0.13 mmol, 95%) 1HNMR (300 MHz, CD3OD) δ 1.11-3.07 (m, 24H), 2.99 (s, 6H), 3.50-3.76 (m, 2H), 3.93 (s, 3H), 4.27-4.44 (m, 1H), 5.05-5.25 (m, 1H), 7.05 (s, 1H) 7.08 (d, J=2.6 Hz, 1H), 7.16 (dd, J=8.8, 2.6 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.64 (dd, J=8.8, 1.5 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 8.16 (br s, 1H). LCMS: m/e 620 (M−H)−, ret time 2.32 min, column A, 4 minute gradient.

Provenance & Evidence