Sodium Hydroxide → 4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.363 g, 0.522 mmol) in TFA (3 mL) was treated with trifluoromethanesulfonic acid (0.232 mL, 2.61 mmol). The reaction was sealed and heated at 80° C. for 30 min, cooled, and poured onto ice. The mixture was basified with 10N NaOH and the reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO and purified by prep HPLC (10-55% MeCN/H2O with 0.1% TFA). Product-containing fractions were treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×) and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.069 g, 0.152 mmol, 29.1% yield). m/z (ESI, +ve ion) 455 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.91 (s, 1H); 8.90 (d, J=2.5 Hz, 1H); 8.48 (d, J=2.5 Hz, 1H); 8.33-8.44 (m, 2H); 7.88 (br. s., 1H); 7.73 (br. s., 1H); 3.93 (s, 3H); 3.57 (br. s., 4H); 2.44 (s, 3H); 2.36-2.43 (m, 4H); 1.35 (s, 6H).

Provenance & Evidence