Hydrochloric Acid → 10-(tert-butoxycarbonyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

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Reaction Steps

Dissolve 10-(1,1-dimethylethyl) 6-methyl 13-cyclohexyl-3-(methyloxy)-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate (5.53 g, 11.02 mmol) in THF (70 ml) with heating, add DMF (20 ml) to maintain solubility, allow to cool to room temperature then add tetrabutylammonium hydroxide (33.1 ml, 33.1 mmol) 10M in methanol. Stir reaction at room temperature for 2 hrs then add 0.1N aqueous 0.1N hydrochloric acid to the reaction followed by 01M aqueous NaH2PO4. Separate phases, wash organic layer sequentially with 1.0N aqueous hydrochloric acid, 0.1M aqueous NaH2PO4. Back extract aqueous 1× using ethyl acetate. Combine ethyl acetate fractions and wash sequentially with 0.1M aqueous NaH2PO4 and brine. Dry over magnesium sulfate, filter and remove solvents in vacuo to yield a bright yellow solid. Dry product in vacuo at room temperature to give 5.2 μg (97%). 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.12-1.28 (m, 2H) 1.28-1.45 (m, 2H) 1.46-1.60 (m, 2H) 1.63 (s, 9H) 1.66-1.96 (m, 4H) 1.96-2.16 (m, 3H) 2.76-2.84 (m, 1H) 3.91 (s, 3H) 4.18 (br.s., 1H) 5.66 (br.s, 1H) 7.00 (d, J=2.44 Hz, 1H) 7.10 (dd, J=8.55, 2.75 Hz, 1H) 7.53 (d, J=8.54 Hz, 1H) 7.65-7.71 (m, 1H) 7.82 (d, J=8.24 Hz, 1H) 7.93 (s, 1H) 8.22 (s, 1H). LC-MS retention time 1.47 min; 486 m/z (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Xterra MS 7u C18 3.0×50 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 2 min, a hold time of 1 min, and an analysis time of 3 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.

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