Tetrahydrofuran → N-(6-methoxypyridin-3-yl)-3-(4-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine

Participants

Reaction Steps

LiHMDS (1.0 M in THF, 557 μL, 0.557 mmol) was added to a stirred solution of 2-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-1,3,5-triazine (68.0 mg, 0.186 mmol) and 3-amino-6-methoxypyridine (Aldrich) (34.6 mg, 0.278 mmol) in THF (928 μL, 0.186 mmol) at 0° C. and the mixture was stirred at the same temperature for 1 h. The reaction mixture was quenched with water (10 mL) and diluted with ethyl acetate (10 mL). The separated aqueous layer was extracted with ethyl acetate (2×10 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (DCM to 5% MeOH in DCM) followed by washing with iPrOH to give N-(6-methoxypyridin-3-yl)-3-(4-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine (15 mg, 17%) as a yellow solid. LCMS (API-ES) m/z 471 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 11.44 (s, 1H) 9.29 (s, 1H) 8.81 (s, 1H) 8.51 (br. s., 1H) 8.29 (br. s., 1H) 8.11 (d, J=9.19 Hz, 1H) 6.85 (d, J=9.19 Hz, 1H) 3.85 (s, 3H) 3.53 (s, 2H) 3.11 (br. s., 4H) 2.87 (s, 3H) 2.75 (s, 3H) 2.34-2.49 (m, 4H).

Provenance & Evidence