Hydrochloric Acid → HCID 178492164, compound

Participants

Reaction Steps

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (122 mg, 0.274 mmol) was suspended in dichloromethane (1.5 mL) and ethanol (1.5 mL), and aniline (0.080 mL, 0.88 mmol) and tetraisopropoxytitanium (0.25 mL, 0.84 mmol) were added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (70° C.-74° C.) and stirred under nitrogen for 45 minutes. Then, the reaction was cooled to room temperature and treated with sodium borohydride (39.8 mg, 1.05 mmol), along with MeOH (about 1 mL). The reaction was stirred at room temperature for 45 minutes, and then MeOH (about 1 mL) and aqueous 5 N HCl (0.55 mL) were added. The reaction flask was put in a preheated oil bath (50° C.-61° C.), stirred for 3.5 hours, and then cooled to room temperature. The resulting suspension was diluted with DCM and MeOH and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM, MeOH, and a 1:1 mixture of these 2 solvents. The filtrate was concentrated, treated with water, and filtered, and the solid was washed with water, collected, and washed with DCM. The solid was then purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((phenylamino)methyl)pyridin-2-amine (92.0 mg, 77% yield). MS (ESI pos. ion) m/z 439 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.56 (br s, 1H), 9.77 (s, 1H), 8.62 (s, 1H), 8.52 (d, J=2.54 Hz, 1H), 8.29 (d, J=1.56 Hz, 1H), 8.15 (dd, J=8.90 Hz, 2.64 Hz, 1H), 7.10 (t, J=7.82 Hz, 2H), 6.85 (d, J=9.00 Hz, 1H), 6.71 (d, J=7.63 Hz, 2H), 6.60 (t, J=6.85 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 2.85 (s, 3H).

Provenance & Evidence