Hydrochloric Acid → HCID 178492168, compound

Participants

Reaction Steps

6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (73.8 mg, 0.166 mmol) was suspended in CH2Cl2 (1.5 mL) and EtOH (1.5 mL), and 2-(aminomethyl)pyridine (0.050 mL, 0.49 mmol) and tetraisopropoxytitanium (0.15 ml, 0.51 mmol) were added via syringe. The reaction was stirred under nitrogen at room temperature for 90 min, and then sodium borohydride (26.3 mg, 0.695 mmol) and MeOH (1.0 mL) were added, and stirring was continued. After 70 min, more MeOH and 5N aqueous HCl (0.50 mL) were added, and stirring was continued 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 DMSO and TFA, and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min using a total flow rate of 100 mL/min) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((pyridin-2-ylmethylamino)methyl)pyridin-2-amine (52.1 mg, 55% yield) as a TFA salt. 1H NMR (d6-DMSO, 400 MHz) δ 12.69 (br s, 1H), 9.81 (br s, 1H), 9.46 (br s, 2H), 8.68 (s, 1H), 8.66 (d, J=4.30 Hz, 1H), 8.56 (d, J=2.74 Hz, 1H), 8.41 (d, J=2.35 Hz, 1H), 8.14 (dd, J=9.00 Hz, 2.74 Hz, 1H), 7.89 (dt, J=7.73 Hz, 1.76 Hz, 1H), 7.51 (d, J=7.82 Hz, 1H), 7.46-7.41 (m, 1H), 6.88 (d, J=8.80 Hz, 1H), 4.41 (s, 2H), 4.29 (s, 2H), 3.85 (s, 3H), 2.86 (s, 3H). m/z (ESI, pos. ion) 454 (M+H)+.

Provenance & Evidence