(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)(4-hydroxypiperidin-1-YL)methanone → (5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone

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Reaction Steps

A solution of (5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone (0.109 g, 0.157 mmol) in TFA (7.0 mL) (Aldrich) was heated at 80° C. overnight. The solution was cooled to room temperature and concentrated to about 50% of the original volume under a stream of argon. A few pieces of ice were added, and then a saturated solution of NaHCO3 was added slowly until pH 7 was reached. The precipitate was isolated by filtration, and the filtercake was washed with water. The solid was suspended in 3 mL of MeOH and 1 mL of THF, then 0.5 mL of 1 N NaOH was added. The suspension was stirred at room temperature for 10 min. The solid was isolated by filtration and dried to give (5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-hydroxypiperidin-1-yl)methanone (0.0406 g, 0.089 mmol, 56.9% yield) as an amorphous yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.08 (s, 1H); 8.85 (d, J=2.3 Hz, 1H); 8.41 (dd, J=4.8, 2.2 Hz, 2H); 8.35 (dd, J=12.6, 2.2 Hz, 1H); 7.96 (br. s., 1H); 7.81 (br. s., 1H); 4.79 (d, J=3.7 Hz, 1H); 3.95 (s, 3H); 3.74 (s, 3H); 3.20-3.27 (m, 2H); 2.44 (s, 3H); 1.76 (br. s., 2H); 1.40 (br. s., 2H). m/z (ESI, +ve ion) 455.0 (M+H)+.

Provenance & Evidence