Tetrahydrofuran → N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)-5-(2-methoxyethoxy)pyridin-2-ylamino)-2-methylpyridin-3-YL)methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a 15 mL round-bottom flask was added 4-(2-fluoro-5-(2-methoxyethoxy)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 335 Step 3) (0.050 g, 0.179 mmol), N-(5-amino-2-methylpyridin-3-yl)methanesulfonamide (0.043 g, 0.215 mmol), and DMF (2.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (Aldrich) (0.145 mL, 0.716 mmol) was then added to the solution in one portion. The now dark burgundy color mixture was stirred at 0° C. for 10 min then warmed up to rt and stirred for 1 h. The reaction mixture was partitioned between sat. NH4Cl and CHCl3. The aqueous layer was extracted with more CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (16 g, 5% to 10% MeOH in DCM) to afford the desired product as a yellow solid (25 mg). MS (ESI pos. ion) m/z: 461.0. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.45 (d, J=2.63 Hz, 6H) 2.52 (s, 3H) 3.06 (s, 3H) 3.61-3.73 (m, 2H) 4.09-4.23 (m, 2H) 7.77 (br. s., 1H) 7.89 (br. s., 1H) 8.17 (d, J=2.92 Hz, 1H) 8.33 (d, J=1.75 Hz, 1H) 8.42 (d, J=3.07 Hz, 1H) 8.65 (s, 1H) 9.29 (br. s., 1H) 11.76 (s, 1H).

Provenance & Evidence