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 (Combi Block, Inc., 2.507 g, 14.30 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (5.24 g, 13.62 mmol), Amphos (bis-4-(di-tert-butylphosphanyl)-N,N-dimethylaniline-dichloropalladium, 0.482 g, 0.681 mmol) and potassium acetate (4.10 g, 41.8 mmol) in ethanol (100 mL) and water (10 mL) was purged with argon and heated at 100° C. overnight. The reaction mixture was cooled, concentrated to remove the EtOH and partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (100 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by ISCO chromatography (hexanes/EtOAc, 15 to 50%) to give 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.62 g, 7.54 mmol, 55.4% yield) as a colorless sticky solid. m/z (ESI, +ve ion) 481.0 (M+H)+.

Provenance & Evidence