1,1'-Carbonyldiimidazole → 13-cyclohexyl-N-isopropylsulfonyl-3-methoxy-6-(3-methyl-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

Participants

Reaction Conditions

Reaction Steps

CDI (80 mg, 0.49 mmol) was added to a solution of tert-butyl 13-cyclohexyl-3-methoxy-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate TFA (200 mg, 0.30 mmol) in THF (1.5 mL) and the reaction mixture was heated at 60° C. for 2 h. The reaction was cooled to rt and then ⅓ (˜0.55 mL) of the reaction solution was added to a stirring solution of propane-2-sulfonamide (40 mg, 0.33 mmol) in DBU (0.20 mL, 1.3 mmol) and THF (0.20 mL). The reaction was stirred at rt ON (complete by LCMS), concentrated to an oil, quenched with 1N HCl (˜1 mL) (prec. formed) and extracted with EtOAc (2×1 mL). The combined organics wee concentrated to dryness, dissolved into MeOH (1.5 mL) and purified by preparative HPLC (CH3CN/H2O with 10 mM NH4OAc) to yield 13-cyclohexyl-N-(isopropylsulfonyl)-3-methoxy-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (28.5 mg, 0.044 mmol, 43% yield) as a yellow solid. 1HNMR (300 MHz, CD3OD) δ ppm 1.13-2.77 (m, 28H), 2.80-2.93 (m, 1H), 3.93 (s, 3H), 3.90-4.02 (m, 1H), 4.27-4.65 (m, 2H), 5.11-5.31 (m, 1H), 7.04 (s, 1H), 7.11 (d, J=2.6 Hz, 1H), 7.16 (dd, J=8.4, 2.6 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.67 (dd, J=8.4, 1.5 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 8.18 (br s, 1H). LC-MS retention time: 2.55 min; m/z 643 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Provenance & Evidence