Reaction Steps
The product from step 1 (256 mg) was mixed with 6N aqueous HCl and heated to reflux for 30 min (HPLC analysis shows complete consumption of SM) and then allowed to cool to rt. The mixture was concentrated in vacuo and then dissolved in water (1 mL) and acetonitrile was added drop wise with stirring (˜10 mL). The mixture was stirred and a precipitate began to form. The mixture was stirred for 1 hour and the precipitate was collected by filtration, washed with acetonitrile and dried in a vacuum oven overnight and this fraction (presumably HCl salt) was set aside. The filtrate was concentrated in vacuo and the process repeated (0.5 mL of water and 20 mL of acetonitrile). The mixture was stirred overnight and then cooled in an ice bath for 1 hour and the precipitate was collected by filtration and dried in a vacuum oven (set aside). The filtrate from this process was poured through a column containing an acidic ion exchange resin. The column was washed with acetonitrile and the product eluted by washing the column with 2M NH3 in MeOH. The filtrate was concentrated to give 46 mg of the title compound as a free base. 1H NMR (300 MHz, DMSO-d6) δ 8.75 (s, 1H), 7.89 (s, 1H), 7.79 (d, 1H), 7.68 (s, 1H), 7.39-7.23 (m, 5H), 7.14 (d, 1H), 6.58 (s, 1H), 5.63 (s, 2H), 3.30-3.12 (m, 2H), 2.92 (d, 1H), 2.58-2.30 (m, 3H), 2.06 (m, 1H), 1.69-1.43 (m, 2H). ES-MS m/z 424.2 [M+H]+, HPLC RT (min) 2.17. Spectral properties of the HCl salt: 1H NMR (300 MHz, DMSO-d6) 9.22 (m, 1H), 9.06 (m, 1H), 8.59 (s, 1H), 8.07 (s, 1H), 7.83 (d, 1H), 7.62 (s, 1H), 7.38-7.25 (m, 5H), 7.13 (d, 1H), 6.78 (s, 1H), 5.62 (s, 2H), 3.64 (m, 1H), 3.52 (d, 1H), 3.31 (d, 1H), 3.09 (dd, 1H), 2.90 (dd, 1H), 2.10 (d, 1H), 1.96-1.69 (m, 3H). ES-MS m/z 424.4 [M+H]+, HPLC RT (min) 2.01.
