Diisopropylethylamine → Methyl 13-cyclohexyl-6-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylate

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Reaction Steps

TBTU (115 mg, 0.361 mmol) was added at rt, in one portion, to a solution containing 13-cyclohexyl-10-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (100 mg, 0.241 mmol), DIEA (0.17 mL, 0.964 mmol), 3-Methyl-3,8-diaza-bicyclo[3.2.1]octane dihydrochloride (115 mg, 0.289 mmol), and DMF (2.4 mL). The solution was maintained for 18 h and concentrated. The resultant residue was charged with dichloromethane (30 mL), washed with water (4×15 mL), washed with brine (15 mL), dried (magnesium sulfate), filtered and concentrated to afford a yellow solid which was used without further purification in the next step. LCMS: retention time: 2.272 min 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 4 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% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode: m/z 524 (MH+). Crude 1H NMR (300 MHz, CDCl3) δ ppm: 8.19 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.77 (dd, J=8.78 Hz, J=1.46 Hz, 1H), 7.61 (m, 1H), 7.49 (m, 3H), 6.96 (s, 1H), 5.2 (s, 1H), 4.41 (s, 1H), 2.81 (m, 4H), 2.51 (s, 1H), 1.95 (m, 15H), 1.29 (m, 11H), 0.76 (m, 2H).

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