Potassium Carbonate → 4-(5-(3,6-Dihydro-2H-pyran-4-YL)-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 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (320 mg, 1.523 mmol) (Frontier Scientific), 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (600 mg, 1.250 mmol), potassium carbonate (400 mg, 2.89 mmol), and Amphos-PdCl2 (50 mg, 0.071 mmol) in dioxane (8 mL) was sparged with argon for 5 min. The mixture was heated at 110° C. under nitrogen. After 14 h, x-phos and Pd2dba3 (40 mg each) were added. After 3 h, more x-phos, Pd2dba3 and boronic ester were added. After 16 h, the mixture was cooled to room temperature, and partitioned between EtOAc (40 mL) and water (20 mL). The aqueous phase was extracted with EtOAc once. The combined organic phase was washed with water (3×), dried over Na2SO4 and concentrated. The residue was purified on silica gel (5 to 30% EtOAc). The dechlorinated fraction came out as the first major peak, followed by the product as the next major peak. The product was collected as a pink solid (130 mg). m/z (ESI, positive ion): 528.2 (M+H)+. 1H NMR (400 MHz, CDCl3-d) δ ppm 2.49-2.58 (m, 5H) 3.79 (s, 3H) 3.91 (s, 3H) 3.95 (t, J=5.38Hz, 2H) 4.31-4.36 (m, 2H) 4.82 (d, J=8.61 Hz, 4H) 6.20 (br. s., 1H) 6.86 (dd, J=11.15, 8.61Hz, 4H) 7.22 (d, J=6.85 Hz, 4H) 8.31 (d, J=1.96 Hz, 1H) 8.50 (dd, J=9.00, 2.54 Hz, 1H).

Provenance & Evidence