Trifluoroacetic acid → HCID 49785435, compound

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(piperazin-1-yl)ethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.350 g, 0.509 mmol) in dichloromethane (10 mL) was treated with triethylamine (0.355 mL, 2.54 mmol). After 10 min, methanesulfonyl chloride (Aldrich; 0.119 mL, 1.526 mmol) was added into the mixture slowly via syringe. After the addition, the reaction mixture was placed into a pre-heated (70° C.) bath and allowed to stir under inert atmosphere for 1.5 h. The heating bath was removed and the mixture was allowed to cool to ambient temperature. The mixture was diluted with chloroform (20 mL) and water (10 mL) and the organic layer was extracted with chloroform (3×10 mL). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated in vacuo. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica-gel column (40 g) eluting with 20% methanol/dichloromethane to give the bis-PMB protected material as a tan oil. This material was diluted with trifluoroacetic acid (1.8 mL, 23.36 mmol) and allowed to stir 5 min. Then trifluoromethanesulfonic acid (0.2 mL, 2.252 mmol) was added into the mixture. The mixture was placed into a pre-heated (70° C.) bath and allowed to stir under inert atmosphere for 10 min. The heating bath was removed and the mixture was allowed to cool to ambient temperature. The mixture was concentrated in vacuo. The mixture was diluted with dichloromethane (10 mL) and sodium carbonate (1.00 g) was added into the mixture, then allowed to stir for 5 min. Then methanol (3 mL) was added into the mixture and allowed to stir 20 min. The mixture was filtered and the filtrate was concentrated in vacuo. The crude product was recrystallized from ethyl acetate/diethyl ether to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.035 g, 0.067 mmol, 17.71% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO) δ 12.23 (s, 1H) 9.36 (s, 1H) 8.92 (s, 1H) 8.74 (s, 1H) 8.39 (s, 1H) 8.05 (s, 1H) 7.91 (s, 1H) 7.79 (m, 2H) 3.59 (m, 1H) 3.10 (s, 4H) 2.86 (s, 3H) 2.50 (d, J=8.80 Hz, 4H) 1.99 (s, 3H) 1.38 (d, J=6.06 Hz, 3H). m/z (ESI, +ve ion) 526.0 (M+H)+.

Provenance & Evidence