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

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.300 g, 0.537 mmol) and benzo[d]thiazol-5-amine (0.202 g, 1.343 mmol) in THF (10 mL) was chilled to 0° C. in an ice bath. Then sodium bis(trimethylsilyl)amide (1.0 M solution in THF, Aldrich; 2.148 mL, 2.148 mmol) was added into the mixture via syringe. After the addition, the ice bath was removed and the mixture was allowed to stir under an inert atmosphere for 1 h. The reaction mixture was diluted with water (30 mL) and the organic layer was extracted with chloroform (3×20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. This gave the crude bis-PMB protected product as a tan oil. This crude material was treated with trifluoroacetic acid (1.8 mL) and trifluoromethanesulfonic acid (0.2 mL). The reaction mixture was placed into a pre-heated bath (70° C.) and allowed to stir under inert atmosphere for 10 min. The mixture was removed from the heat source and allowed to cool to ambient temperature. The mixture was concentrated in vacuo. The crude residue was diluted with DCM (10 mL), and then sodium carbonate (1.5 g) was added to the mixture with stirring. The mixture was filtered and concentrated in vacuo. The crude was purified by reverse phase HPLC (Varian, 5-70% acetonitrile in water with trifluoroacetic acid as additive 0.1% v/v in each solvent) to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-morpholinoethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.015 g, 0.033 mmol, 6.23% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO) δ 12.24 (s, 1H) 9.36 (s, 1H) 8.92 (s, 1H) 8.75 (s, 1H) 8.36 (s, 1H) 8.06 (d, J=8.61 Hz, 1H) 7.92 (s, 1H) 7.82 (d, J=8.61 Hz, 2H) 3.57 (s, 4H) 3.29-3.46 (m, 1H) 2.50 (d, J=7.82 Hz, 5H) 2.34 (s, 2H) 1.36 (d, J=6.46 Hz, 3H). m/z (ESI, +ve ion) 449.1 (M+H)+.

Provenance & Evidence