Trifluoroacetic acid → 4-(2-(2-Methoxypyrimidin-5-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of N,N-bis(4-methoxybenzyl)-4-(2-(2-methoxypyrimidin-5-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (301 mg, 0.414 mmol) in trifluoroacetic acid (638 μL, 8.28 mmol) was treated with a couple of drops of trifluoromethanesulfonic acid and the mixture was heated at 80° C. overnight. After cooling, the mixture was concentrated and the residue was dissolved in 5% (2 M NH3 in MeOH)/DCM (5 mL) and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (pure DCM→3% MeOH in DCM). The isolated yellow solid was dissolved in DMSO and was subjected to a reversed phase preparative HPLC purification (10% MeCN in H2O to 100% MeCN w/0.10% (v/v) TFA). The product fraction was basified with saturated NaHCO3 (aq), extracted with dichloromethane (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated to give 4-(2-(2-methoxypyrimidin-5-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (65 mg, 0.134 mmol, 32.3% yield) as a bright yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.78 (s, 1H); 9.03 (s, 2H); 8.73 (d, J=1.56 Hz, 1H); 8.23 (d, J=1.76 Hz, 1H); 7.91 (br. s., 1H); 7.75 (br. s., 1H); 3.91 (s, 3H); 3.50 (s, 2H); 3.11 (br. s., 4H); 2.86 (s, 3H); 2.46-2.49 (m, 4H); 2.44 (s, 3H). m/z (ESI, +ve ion) 486.8 (M+H)+.

Provenance & Evidence