Hydrochloric Acid → HCID 178492170, compound

Participants

Reaction Steps

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (102.5 mg, 0.230 mmol) was suspended in dichloromethane (1.3 mL) and EtOH (1.3 mL), and 4-(aminomethyl)pyridine (0.070 mL, 0.69 mmol) and tetraisopropoxytitanium (0.20 mL, 0.68 mmol) were added. The reaction was stirred under nitrogen at room temperature. After 50 min, sodium borohydride (30.8 mg, 0.814 mmol) and MeOH (1 mL) were added, and stirring was continued at room temperature. After 1 h, more MeOH and 5 N aqueous HCl (0.60 mL) were added, and stirring was continued at room temperature over the weekend. Then, the reaction was treated with DCM and MeOH and was filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and treated with DCM and TFA and some DMSO (about 1 mL) and concentrated. The material was dissolved in water and partially concentrated resulting in the formation of a precipitate. The suspension was filtered, and the solid was washed with MeOH. The solid was set aside. The filtrate was concentrated and filtered again. The solid was combined with the solid collected from the first filtration. The filtrate was concentrated and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 minutes with a total flow of 100 mL/min). The fractions with product were combined with the solid that had been collected, concentrated, and dried under high vacuum, first at about 50° C., and then at room temperature overnight to afford N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((pyridin-4-ylmethylamino)methyl)pyridin-2-amine (126.6 mg, 96.7% purity, 97% yield) as a TFA salt. 1H NMR (D2O, 400 MHz) δ 8.83-8.77 (m, 4H), 8.43 (s, 1H), 8.21 (dd, J=8.41 Hz, 2.35 Hz, 2H), 8.08-8.03 (m, 3H), 7.82 (dd, J=9.00 Hz, 2.74 Hz, 1H), 6.95 (dd, J=9.00 Hz, 1H), 4.63 (s, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 3.91 (s, 3H), 2.69 (s, 3H). m/z (ESI, pos. ion) 454 (M+H)+.

Provenance & Evidence