Reaction Steps
To a solution of 4-aminobutyraldehyde diethyl acetal (12.5 mL, 63.3 mmol) in Et2O (25 mL) was added methyl vinyl ketone (6.70 mL, 82.3 mmol). After 1 h, concentrated HCl (35 mL) was added, and the reaction mixture was heated at 100° C. for 3 h. After the mixture was concentrated, the residue was diluted with EtOH (25 mL), and 1-(3-bromophenyl)-1-methylhydrazine hydrochloride (3.90 g, 15.9 mmol) was added followed by concentrated HCl (25 mL). The reaction was heated at reflux overnight. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 9-bromo-7-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (0.95 g, 39%) as an orange solid. 9-Bromo-7-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (0.15 g, 0.49 mmol) was reacted according to the procedure of Example 2 (step b) to give a yellow oil in 20% (46 mg). The yellow oil was dissolved in CH3OH (1 mL) and was treated with 2 N HCl in Et2O (1 mL). The resulting solid was isolated by filtration and dried under vacuum to give the title compound (49 mg, 99%) as a yellow powder: mp 235-240° C.; 1H NMR (500 MHz, CD3OD) δ 9.10 (d, J=2.0 Hz, 1H), 8.41 (dd, J=8.5, 2.5 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.85 (d, J=7.5 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.16 (dd, J=8.5, 2.0 Hz, 1H), 7.03 (d, J=1.5 Hz, 1H), 6.89 (dd, J=7.0, 2.0 Hz, 1H), 5.15 (t, J=7.0 Hz, 1H), 3.77 (s, 3H), 3.77-3.71 (m, 4H), 3.49-3.44 (m, 1H), 3.28-3.25 (m, 1H), 2.76-2.72 (m, 1H), 2.31-2.19 (m, 3H); ESI MS m/z 465 [M+H]+; HPLC (Method A) 97.2% (AUC), tR=12.8 min.
