Hydrochloric Acid → 2-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-(tetrahydrofuran-2-ylmethyl)-1H-indole-5-carboxamide hydrochloride

Participants

Reaction Steps

Starting materials: methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate and tetrahydrofurfurylamine, but heated at reflux for 2 h. The cooled mixture was poured into a saturated NaHCO3 solution and concentrated in vacuo. The residue was suspended in methanol/dichloromethane, (1:1), silica gel (˜2 g) was added and the mixture was re-concentrated in vacuo. The resulting residue was purified on a silica gel column using dichloromethane/methanol, (100:1 to 25:2 and 1% ammonia solution in water (25%)), as the eluent to give the base. Yield: 27%: 1H NMR (DMSO-d6, 300 MHz) δ 14.75 (br s, 1H), 11.37 (br s, 1H), 10.69 (s, 1H), 8.50 (t, J=5.51 Hz, 1H), 8.22 (s, 1H), 8.06 (d, J=9.2 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J=9.2 Hz, 1H), 7.54 (d, J=8.1 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 4.25 (s, 2H), 4.02-3.60 (m, 6H), 3.44-3.22 (m, 4H), 3.20-3.03 (m, 2H), 1.95-1.78 (m, 4H), 1.70-1.55 (m, 1H); MS (ES) m/z 437 (M++1). The base was transferred to the hydrochloride.

Provenance & Evidence