Hydrochloric Acid → HCID 178492169, compound

Participants

Reaction Steps

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (113.7 mg, 0.255 mmol) was suspended in dichloromethane (1.3 mL) and ethanol (1.3 mL), and 3-(aminomethyl)pyridine (0.080 mL, 0.79 mmol) and tetraisopropoxytitanium (0.23 mL, 0.78 mmol) were added. The reaction was stirred under nitrogen at room temperature. After 85 min, sodium borohydride (33.8 mg, 0.893 mmol) and MeOH (1 mL) were added, and stirring was continued at room temperature. After another 70 min, 5 N HCl (0.50 mL) was added, along with MeOH, and stirring was continued at room temperature for 3 days. More 5 N HCl (0.20 mL) and MeOH were added, and stirring was continued at room temperature overnight. The suspension was diluted with DCM and MeOH and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated, treated with DCM, MeOH, TFA, and concentrated again. The material was dissolved with water and MeOH and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min with a total flow rate of 100 mL/min). The HPLC fractions with product were collected, concentrated, and dried under high vacuum, first in a water bath at 50° C., and then at room temperature overnight to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((pyridin-3-ylmethylamino)methyl)pyridin-2-amine (117.1 mg, 81% yield) as a TFA salt. 1H NMR (D2O, 400 MHz) δ 8.94 (s, 1H), 8.92-8.87 (m, 1H), 8.83 (d, J=5.87 Hz, 1H), 8.69 (d, J=8.22 Hz, 1H), 8.47 (s, 1H), 8.37 (s, 1H), 8.26 (d, J=2.15 Hz, 1H), 8.13-8.06 (m, 1H), 7.98 (dd, J=9.19 Hz, 2.54 Hz, 1H), 7.11 (d, J=9.19 Hz, 1H), 4.61 (s, 2H), 4.44 (s, 2H), 3.99 (s, 3H), 2.73 (s, 3H). m/z (ESI, +ve ion) 454 (M+H)+.

Provenance & Evidence