Trifluoroacetic acid → N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-yl)benzo[d]thiazol-5-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.500 g, 0.918 mmol) and benzo[d]thiazol-5-amine (0.276 g, 1.836 mmol) in THF (10 mL) was cooled to −20° C. and treated dropwise with 1.0 M lithium bis(trimethylsilyl)amide in THF (3.21 mL, 3.21 mmol). The mixture was allowed to slowly warm to ambient temperature while stirring under inert atmosphere for 1 h. The reaction mixture was diluted with water (50 mL) and extracted with CHCl3 (3×50 mL). The combined organic extracts were dried over Na2SO4. The solution was filtered and concentrated to give the crude product as a tan solid. This was purified by chromatography through a SiliCycle SiliaSep pre-packed silica gel column (80 gram) eluting with a gradient of 10% to 100% EtOAc in hexane over 30 minutes, followed by a gradient of 1-20% MeOH/DCM over 25 min to give the bis-PMB protected material (0.437 g) as a tan oil. This was treated with a mixture of trifluoroacetic acid (1.8 mL, 23.36 mmol) and trifluoromethanesulfonic acid (0.2 mL, 2.252 mmol) and the resulting solution was heated at 70° C. 20 min. The mixture was cooled to ambient temperature and concentrated to give a tan oil. The mixture was dissolved in DCM (10 mL) and allowed to stir 5 min, then sodium carbonate (2.5 grams) was slowly added to the mixture and allowed to stir vigorously for 20 min. The solid was collected by filtration and rinsed with dichloromethane (2×30 mL) followed by water (3×20 mL). The solid was dried to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.155 g, 0.357 mmol, 38.9% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO) δ 12.25 (s, 1H); 9.36 (s, 1H); 8.91 (s, 1H); 8.76 (s, 1H); 8.33 (s, 1H); 8.06 (d, J=8.80 Hz, 1H); 7.94 (s, 1H); 7.80 (s, 2H); 3.58 (s, 4H); 3.46 (s, 2H); 2.44-2.54 (m, 3H); 2.39 (s, 4H). m/z (ESI, +ve ion) 435 (M+H)+.

Provenance & Evidence