Trifluoroacetic acid → HCID 59548467, compound

Participants

Reaction Steps

To a slurry of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinonitrile (Example 143, 0.205 g, 0.346 mmol) in 7 mL THF at 0° C. was added tetraisopropoxytitanium (0.122 mL, 0.415 mmol) followed by ethylmagnesium bromide 1.0 M in THF (2.214 mL, 2.214 mmol). The reaction became dark brown. After 30 min, boron trifluoride diethyl etherate (0.210 mL, 1.660 mmol) was added. The reaction was warmed to ambient temperature, and after 15 min, quenched with 10N NaOH. The aqueous was extracted 3× EtOAc. The combined extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to give 0.234 g. This material treated with 2 mL TFA and triflicacid (0.154 mL, 1.730 mmol). The reaction was sealed, and heated to 80° C. for min. The reaction was cooled and pour onto ice, basified with 10N NaOH and extracted 3× DCM. The combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting material was treated with DMSO and TFA purified by RPHPLC, 10-60% ACN/H2O (+0.1% TFA); Product-containing fractions were concentrated and treated with sat'd aq. NaHCO3 and DCM. The aqueous layer was extracted 3×10% IPA/DCM and combined organics dried over sodium sulfate, filtered, and concentrated in vacuo to give 4-(5-(3-aminopentan-3-yl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.018 g, 0.044 mmol, 12.62% yield) as a yellow solid. m/z (ESI, +ve ion) 413 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.92 (s, 1H), 8.88 (d, J=2.5 Hz, 1H), 8.35-8.46 (m, 3H), 7.88 (br. s., 1H), 7.72 (br. s., 1H), 3.93 (s, 3H), 2.44 (s, 3H), 1.53-1.84 (m, 4H), 0.69 (t, J=7.3 Hz, 6H).

Provenance & Evidence