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

Participants

Reaction Conditions

Reaction Steps

Lithium bis(trimethylsilyl)amide (Acros, Morris Plains, N.J.; 1.0M solution in THF/ethyl benezene) (0.599 mL, 0.599 mmol) was added dropwise to a solution of 6-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-2-methylpyrimidin-4-amine (124.0 mg, 0.200 mmol) and 6-methoxypyridin-3-amine (0.037 mL, 0.300 mmol) in THF (3.0 mL) at 0° C., and the resulting dark brown solution was stirred at 0° C. for 1 h. Excess LiHMDS was quenched by the addition of sat. aq. NH4Cl (5 mL), and the resulting mixture was partitioned between EtOAc (50 mL) and half-sat. aq. NH4Cl (15 mL). The organic layer was separated, washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (ISCO, 12 g, 0 to 10% MeOH/DCM) furnished N,N-bis(4-methoxybenzyl)-6-(2-(6-methoxypyridin-3-ylamino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-2-methylpyrimidin-4-amine (137.7 mg, 0.190 mmol, 95% yield) as a brown solid. 1H NMR (400 MHz, CDCl3) δ 11.67 (br. s., 1H); 8.36 (d, J=2.54 Hz, 1H); 8.06-8.11 (m, 2H); 7.54 (br. s., 1H); 7.18 (d, J=7.43 Hz, 4H); 6.84-6.90 (m, 4H); 6.75 (d, J=8.80 Hz, 1H); 6.56 (s, 1H); 4.77 (br. s., 4H); 3.93 (s, 3H); 3.80 (s, 6H); 3.42 (br. s., 2H); 3.19 (br. s., 4H); 2.76 (s, 3H); 2.65 (s, 3H); 2.50 (br. s., 4H). m/z (ESI, +ve ion) 561.2 (M-piperazine sulfonamide)+.

Provenance & Evidence