Trifluoromethanesulfonic acid → (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A dark red solution of (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.097 g, 0.124 mmol) and trifluoromethanesulfonic acid (0.055 mL, 0.620 mmol) in 1 mL TFA was sealed and heated to 80° C. for 30 min. The reaction was cooled with ice, then quenched with 10 N NaOH until basic, and partitioned between water and DCM. The aqueous layer was extracted with DCM 2 times, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. This material was dissolved in DMSO (plus a few drops TFA) and purified by RPHPLC, 10-80% ACN/H2O (plus 0.1% TFA); product-containing fractions were concentrated to dryness, then treated with sat'd aq. NaHCO3 and DCM. The aq. layer was extracted 3×DCM and combined organics dried over sodium sulfate, filtered, and concentrated in vacuo to give (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine as a yellow solid (0.021 g, 0.039 mmol, 31% yield). m/z (ESI, +ve ion) 542 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.58 (br. s., 1H), 8.69 (br. s., 1H), 8.17-8.34 (m, 2H), 7.92 (br. s., 1H), 5.38 (br. s., 2H), 3.97 (s, 3H), 3.47-3.62 (m, 1H), 3.11-3.31 (m, 5H), 2.77 (br. s., 3H), 2.49-2.68 (m, 7H), 1.44 (d, J=6.1 Hz, 3H), 1.27 (d, J=6.8 Hz, 6H).

Provenance & Evidence