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

4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (744 mg, 0.992 mmol) was dissolved in trifluoroacetic acid (Aldrich, redistilled, 99+%, 10 mL) and the flask was fitted with a reflux condenser and placed in a preheated oil bath (75° C.) and stirred overnight. Then, the reaction was cooled to room temperature, concentrated, diluted with DCM (30 mL), and treated with saturated sodium bicarbonate (30 mL) and with 5 N NaOH to raise the pH of the aqueous phase to about 7. The layers were separated, and the aqueous phase was extracted with DCM and with 10:1 DCM/MeOH). The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; 100:1 DCM/MeOH to 75:1 DCM/MeOH to 50:1 DCM/MeOH). The fractions with product were collected, concentrated, and purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min using a total flow rate of 100 mL/min) to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)phenyl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (187.7 mg 36% yield). 1H NMR (CDCl3, 400 MHZ) δ 11.60 (s, 1H), 8.73 (d, J=2.35 Hz, 1H), 8.24 (d, J=2.74 Hz, 1H), 8.06 (dd, J=11.93 Hz, 1.76 Hz, 1H), 8.01 (d, J=2.35 Hz, 1H), 7.90 (d, J=8.41 Hz, 2H), 7.45 (d, J=8.22 Hz, 2H), 4.30-4.23 (m, 1H), 4.04 (s, 3H), 2.64 (s, 3H), 1.74 (d, J=7.24 Hz, 3H). m/z (ESI, pos. ion) 510 (M+H)+.

Provenance & Evidence