Water → Tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 51) (20 g, 52.0 mmol), 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (Example 34, Step 3) (21.15 g, 62.4 mmol), potassium acetate (8.12 mL, 130 mmol), and Amphos (bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.) (1.913 g, 2.70 mmol) in p-dioxane (300 mL, 3528 mmol) and water (60 mL, 52.0 mmol) contained in a 1 L 3 neck round-bottomed flask was stirred at 100° C. overnight. The solution was partitioned between water and EtOAc and the organic layer was separated, washed with water, dried over Na2SO4, filtered and concentrated in vacuo to give the crude product which was adsorbed onto silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (Teledyne ISCO, Lincoln, Nebr.) (330 g) eluting with a gradient of 10% to 50% EtOAc in hexane to give tert-butyl 4-((5-(4-(bis (4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (25.2 g, 39.1 mmol, 75% yield). m/z (ESI, positive ion) m/z 644 (M+H)+.

Provenance & Evidence