Hydrochloric Acid → N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine

Participants

Reaction Conditions

Reaction Steps

6-(2-Fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (171.2 mg, 0.3694 mmol) and 4-aminoindole (Aldrich, St. Louis, Mo., 69.2 mg, 0.524 mmol) were suspended in EtOH (2.0 mL) and hydrochloric acid (J. T. Baker, Phillipsburg, N.J., 5N, 0.090 mL, 0.45 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.) and stirred for about 105 minutes. Then, the reaction was cooled to room temperature and diluted with MeOH and 2N ammonia in MeOH. The reaction was concentrated and treated with DMF and DCM and filtered. The filtrate was filtered again, and the solid was again washed with DCM. This filtrate was concentrated and purified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 ml/min). The fractions with product were collected, concentrated, and filtered through a silica gel filter (about 1 inch, 10:1 DCM/2N ammonia in MeOH) to give N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (13.1 mg, 7% yield). MS (ESI pos. ion) m/z 492 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.49 (s, 1H), 11.17 (s, 1H), 9.84 (s, 1H), 8.64 (s, 1H), 8.33 (s, 1H), 8.04 (d, J=6.85 Hz, 1H), 7.38-7.32 (m, 3H), 7.12-7.04 (m, 2H), 6.93 (d, J=8.80 Hz, 2H), 6.72 (s, 1H), 4.53 (s, 2H), 4.51 (s, 2H), 3.75 (s, 3H), 2.92 (s, 3H).

Provenance & Evidence