Lithium Hexamethyldisilazide → N-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-chloropyridin-3-YL)-4-fluorobenzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.08 g, 0.265 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (0.795 mL, 0.795 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min before 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.142 g, 0.318 mmol) was added. The resulting mixture was stirred at 0° C. for 10 min then removed from the ice bath and stirred for 3 h. The reaction mixture was quenched with water. The resulting mixture was partitioned between EtOAc and sat. NH4Cl. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 20% to 30% acetone in hexanes) to give the product as a yellow solid (0.090 g). m/z (ESI, +ve ion) 727.1 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 12.48 (s, 1H); 8.78-8.95 (m, 2H); 8.41 (d, J=3.51Hz, 1H); 8.27 (s, 1H); 7.93 (dd, J=8.62, 4.97 Hz, 2H); 7.22 (d, J=6.58 Hz, 4H); 7.14 (t, J=8.48 Hz, 2H); 6.77-6.97 (m, 6H); 4.85 (d, J=3.36 Hz, 4H); 3.81 (d, J=5.12 Hz, 6H); 2.61 (s, 3H).

Provenance & Evidence