Cesium fluoride → 1-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)ethanone

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 4-(5-chloro-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 313, Step 2; 0.6020 g, 1.000 mmol), X-Phos-Pd(OAc)2 re-milled mix (1:1, 0.070 g, 0.100 mmol), and cesium fluoride (0.129 mL, 3.50 mmol) in 1,4-dioxane (5.00 mL, 58.5 mmol) was treated with tributyl(1-ethoxyvinyl)stannane (0.507 mL, 1.500 mmol) under nitrogen. The mixture was sealed and heated at 110° C. for 16 h. The reaction mixture was then cooled to room temperature and passed through a short plug of Celite® (diatomaceous earth). The filter cake was washed with EtOAc (3×20 mL) and the combined filtrates were concentrated in vacuo. The residue was loaded onto a short column of silica gel, tin byproducts were eluted with DCM, and the desired product was then eluted with 5% MeOH/DCM to give a mixture of desired product and a small amount of dechlorinated product. Chromatographic purification of this mixture (silica gel, 0% to 30% EtOAc/hexanes) gave 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (0.482 g, 0.791 mmol, 79% yield) as a light yellow solid. m/z (ESI, positive ion) 610 (M+H)+.

Provenance & Evidence