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

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Reaction Conditions

Reaction Steps

A mixture of 5-chloro-2-fluoropyridin-3-ylboronic acid (1220 mg, 6.96 mmol) (Asymchem Laboratories, Inc.), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (2300 mg, 5.98 mmol), and potassium acetate (1200 mg, 12.23 mmol) in dioxane (10 mL)-water (2.0 mL) was placed in a 100 mL flask under argon. A-Phos-PdCl2 (150 mg, 0.212 mmol) was added and the mixture was heated to 95° C. under nitrogen. After 2 h, more boronic acid (600 mg) was added and the mixture was heated for another hour. The mixture was cooled to rt. Saturated NH4Cl was added. The mixture was partitioned between water (5 mL) and EtOAc (30 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was purified on silica gel using 10-50% EtOAc in hexane to give the desired product as a light yellow solid (2.3 g). LCMS (ES, pos.): calcd for C25H23ClFN5O2: 479.2; found: 480.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.53 (dd, J=8.02, 2.74 Hz, 1H); 8.25 (d, J=1.37 Hz, 1H); 7.21 (d, J=8.41 Hz, 4H); 6.86 (t, J=8.22 Hz, 4H); 4.81 (d, J=7.24 Hz, 4H); 3.80 (2s, 6H); 2.54 (s, 3H).

Provenance & Evidence