Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 4-(5-chloro-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 5-chloro-2-fluoropyridin-3-ylboronic acid (454 mg, 2.59 mmol) (Combi-Blocks Inc.), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (950 mg, 2.468 mmol), Amphos 2 (87 mg, 0.123 mmol) and potassium acetate (744 mg, 7.58 mmol) (Aldrich) in EtOH (15 mL) and water (1.5 mL) was purged with argon and heated in a microwave reactor at 100° C. for 30 min. The reaction mixture was concentrated to remove the EtOH and partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was further extracted with EtOAc (20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified on the ISCO (40 g column, eluent: 30-80% EtOAc in hexanes) to give 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (913 mg, 1.902 mmol, 77% yield) as a pale yellow sticky solid. The material was used in the next step without further purification. m/z (ESI, +ve ion) 480.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.53 (1H, dd, J=7.9, 2.6 Hz); 8.25 (1H, dd, J=2.6, 1.3 Hz); 7.21 (4H, d, J=8.6 Hz); 6.80-6.90 (4H, m); 4.82 (2H, s); 4.80 (2H, s); 3.81 (3H, s); 3.80 (3H, s); 2.54 (3H, s).

Provenance & Evidence