Ethanol → 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of potassium acetate (0.38 g, 3.87 mmol), 2-fluoro-3-pyridineboronic acid (0.28 g, 1.987 mmol) and 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.60 g, 1.559 mmol) in DCM (8.0 mL) was evaporated under nitrogen to dryness. THF (5.0 mL) was added followed by the addition of bis[4-(di-tert-butylphosphino)-N,N-dimethylaniline]palladium dichloride (Am-phos) (0.060 g, 0.085 mmol). The mixture was heated in an oil bath at 80° C. After 1 h, EtOH (5 mL) was added and heating was continued overnight. The mixture was cooled to rt. Water (10 mL) and DCM (10 mL) were added. The organic layer was separated. The aqueous layer was extracted with CH2CL2 and the organic layer was dried over MgSO4. The solution was filtered and concentrated in vacuo. The orange oil was adsorbed onto a plug of silica gel and purified by chromatography eluting with 2:1 hexane-acetone to provide 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (80 mg, 0.180 mmol, 11.52% yield) as a white foam. LCMS (ES, pos.): calcd for C25H24FN5O2: 445.2; found: 446.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.49-8.62 (m, 1H); 7.86-7.99 (m, 1H); 7.27-7.36 (m, 1H); 7.23 (dd, J=8.31, 4.99 Hz, 4H); 6.87 (t, J=8.51 Hz, 4H); 3.81 (s, 3H) 4.81 (s, 4H); 3.80 (s, 3H); 2.55 (s, 3H).

Provenance & Evidence