6-Methoxy-3-pyridinylamine → 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Steps

A solution of 6-methoxypyridin-3-amine (354 mg, 2.85 mmol) (Aldrich) and 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) in THF (15 mL) was cooled to 0° C. in an ice bath and treated dropwise with 1 M LiHMDS (5.71 mL, 5.71 mmol). After stirring for 1 h at this temperature, the reaction mixture was quenched with a saturated solution of NH4Cl at 0° C. and extracted with EtOAc (50 mL), dried over MgSO4, filtered and concentrated. Purification on the ISCO (40 g column, 20-100% EtOAc in hexanes) gave 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (717.3 mg, 1.228 mmol, 64.6% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 584.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.65 (1H, s); 8.73 (1H, d, J=2.7 Hz); 8.26 (1H, d, J=2.7 Hz); 8.19 (1H, d, J=2.7 Hz); 7.83 (1H, dd, J=8.8, 2.7 Hz); 7.19 (4H, dd, J=16.2, 8.6Hz); 6.86 (4H, dd, J=10.4, 8.8 Hz); 6.70 (1H, d, J=8.8 Hz); 4.86 (2H, s); 4.81 (2H, s); 3.93 (3H, s); 3.81 (3H, s); 3.79 (3H, s); 2.57 (3H, s).

Provenance & Evidence