Ammonium Chloride → (R)-N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Steps

(R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (19.64 g, 30.9 mmol) and 5-amino-2-methoxypyridine (4.13 mL, 33.3 mmol) were dissolved in THF (300 mL) in a 2-necked round bottomed flask equipped with a stirbar and a dropping funnel. To the dropping funnel was added lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran/ethylbenzene (Acros; 96.0 mL, 96 mmol) via cannula, and the reaction flask was cooled in an ice water bath under nitrogen. Then, the LiHMDS solution was added to the reaction mixture dropwise over 20 min. The reaction mixture was subsequently stirred for 30 min and saturated ammonium chloride (40 mL) was then added dropwise via the dropping funnel, followed by water (200 mL). The reaction was warmed to room temperature and diluted with EtOAc (150 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatogtraphic purification of the residue (silica gel, 75:1 DCM/MeOH to 50:1 DCM/MeOH to 50:1 DCM/2N ammonia in MeOH to 40:1 DCM/2N ammonia in MeOH) provided (R)—N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (18.47 g).

Provenance & Evidence