N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine → 4-(2-(6-Methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (459.4 mg, 0.6277 mmol) was dissolved in trifluoroacetic acid (Aldrich, redistilled, 99+%, 7.5 mL) and the flask was fitted with a reflux condenser and put in a preheated oil bath (75° C.) and stirred overnight. Then, the reaction was cooled to room temperature, concentrated, diluted with DCM, and treated with saturated sodium bicarbonate and 5N NaOH to raise the pH of the aqueous phase to about 6. The layers were separated, and the aqueous phase was extracted with DCM. The organic phases were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel column (25:1 DCM/MeOH to 20:1 DCM/MeOH). The fractions with product were collected, concentrated, treated with MeOH, and filtered. The solid was washed with MeOH, but was still not 95% pure by HPLC. So, the filtrate and solid were combined, concentrated, treated with EtOAc and acetone (which in combination dissolved the compound), concentrated, and purified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min; total flow rate of 100 mL/min) to give 4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (192.4 mg). 1H NMR (CDCl3, 400 MHz) δ 8.87 (s, 1H), 8.48 (s, 1H), 8.16 (d, J=1.57 Hz, 1H), 8.07 (d, J=8.02 Hz, 1H), 7.91 (d, J=8.22 Hz, 2H), 7.45 (d, J=8.22 Hz, 2H), 6.93 (d, J=9.00 Hz, 1H), 4.28 (q, J=7.56 Hz, 1H), 4.03 (s, 3H), 3.06 (s, 3H), 2.63 (s, 3H), 1.74 (d, J=7.04 Hz, 3H). m/z (ESI, pos. ion) 492 (M+H)+.

Provenance & Evidence