Hydrochloric Acid → HCID 178492172, compound

Participants

Reaction Steps

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (99.5 mg, 0.223 mmol) was suspended in CH2Cl2 (1.5 mL) and ethanol (1.5 mL), and tert-butylamine (0.075 mL, 0.71 mmol) and tetraisopropoxytitanium (0.20 mL, 0.68 mmol) were added. The reaction was stirred under nitrogen at room temperature for 20 min, and then was fitted with a reflux condenser and put in a preheated oil bath (about 50° C.) and stirred for 90 min. Then, the reaction was cooled to room temperature and sodium borohydride (28.7 mg, 0.759 mmol) and MeOH (1.0 mL) were added. The reaction was stirred at room temperature for 45 minutes, and then more MeOH and 5 N HCl (0.50 mL) were added, and stirring was continued overnight at room temperature. Then, the reaction 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 and diluted with DCM and MeOH and filtered through another Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and purified by prep HPLC to give 5-((tert-butylamino)methyl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (51.1 mg, 98.3% purity, 43% yield) as a TFA salt. 1H NMR (d6-DMSO, 400 MHz) δ 12.74 (br s, 1H), 9.81 (br s, 1H), 8.70 (s, 1H), 8.65 (br s, 2H), 8.59 (d, J=2.74 Hz, 1H), 8.42 (d, J=2.35 Hz, 1H), 8.14 (dd, J=8.80 Hz, 2.74 Hz, 1H), 6.89 (d, J=8.80 Hz, 1H), 4.18 (br s, 2H), 3.86 (s, 3H), 2.87 (s, 3H), 1.39 (s, 9H). m/z (ESI, +ve ion) 419 (M+H)+.

Provenance & Evidence