Trifluoroacetic acid → HCID 59548189, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (Example 271, 0.270 g, 0.443 mmol), titanium (iv) isopropoxide (0.519 mL, 1.772 mmol) and isopropylamine (0.152 mL, 1.772 mmol) in 3 mL THF was sealed and heated to 60° C. overnight. The reaction was cooled, diluted with 3 mL DCM and treated with sodium triacetoxyborohydride (0.375 g, 1.772 mmol). After 1 h, sodium cyanoborohydride (0.111 g, 1.772 mmol) was added. After 3 h, the reaction was complete. The reaction was treated with ice, water, conc. NH4OH, and DCM. The organic layer was removed. Upon attempted extraction, only an emulsion was possible, so the material was filtered through celite. The aq. layer was extracted 1×DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo to give 0.331 g of an orange oil containing impure 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(1-(isopropylamino)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine. m/z (ESI, +ve ion) 653 (M+H)+. The impure material was treated with 2 mL TFA and triflic acid (0.197 mL, 2.214 mmol) in a sealed vessel, and was heated to 80° C. for 30 min. The reaction was cooled and poured onto ice, and basified with 10N NaOH. The material was extracted with DCM, three times, and 10% iPrOH/DCM once. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting solid was suspended in MeOH and filtered, rinsing with MeOH. The solid was dried in vacuo to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(1-(isopropylamino)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.145 g, 0.352 mmol, 79% yield) as an orange solid. m/z (ESI, +ve ion) 413 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.91 (s, 1H), 8.77 (br. s., 1H), 8.28-8.49 (m, 3H), 7.89 (br. s., 1H), 7.74 (br. s., 1H), 3.93 (s, 3H), 3.76-3.91 (m, 1H), 3.26-3.32 (m, 1H), 2.44 (s, 3H), 1.27 (br. s., 3H), 0.84-1.08 (m, 6H).

Provenance & Evidence