Methyl iodide → tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

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A solution of 3-bromophenylhydrazine hydrochloride (15.75 g, 70.33 mmol) and tert-butyl 4-oxoazepane-1-carboxylate (15.05 g, 70.33 mmol) in 15:2 EtOH/(12 N HCl solution) (102 mL) was stirred at reflux overnight. The solution was concentrated under reduced pressure to afford a red oil. Boc2O (46.00 g, 211.0 mmol) was added to a suspension of the red oil and K2CO3 (29.12 g, 211.0 mmol) in 1:1 H2O/i-PrOH (180 mL), and the resulting suspension was stirred at 25° C. for 2 h. H2O was added, and the resulting suspension was filtered. The filtrate was extracted with CH2Cl2, and the combined extracts were dried over Na2SO4. The resulting solution was concentrated under reduced pressure, and flash chromatography (silica gel, hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a viscous red oil. NaH (60% dispersion in oil, 5.626 g, 140.7 mmol) was added to a solution of the viscous red oil in DMF (60 mL) under N2, and the resulting suspension was stirred at 25° C. for 45 min. MeI (6.6 mL, 106 mmol) was added to the suspension, and the resulting suspension was stirred at 25° C. for 2 h. H2O was added, and the aqueous solution was extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (1.62 g, 6%) as a yellow foam and the title compound (2.80 g, 9%) as a white foam: 1H NMR (300 MHz, CDCl3) δ 8.28 (br s, 0.5H), 8.21 (br s, 0.5H), 7.34 (dd, J=8.4, 1.5 Hz, 1H), 7.30-7.22 (1H, overlapping with solvent), 3.85-3.63 (m, 4H), 3.39-3.32 (m, 2H), 2.99-2.91 (m, 2H), 1.68 (s, 4.5H), 1.67 (s, 4.5H), 1.48 (s, 9H).

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