Sodium bis(trimethylsilyl)amide → N-(2-Chloro-5-(3-(2-methyl-6-(methylthio)pyrimidin-4-YL)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-YL)methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a flame dry 15 mL round-bottom flask was added 4-(1-(6-fluoro-5-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyridin-3-yl)ethyl)morpholine (0.160 g, 0.459 mmol), N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (0.122 g, 0.551 mmol), and THF (4.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (Aldrich) (1.837 mL, 1.837 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 quenched with sat. NH4Cl. The reaction mixture was partitioned between water and CHCl3. The aqueous layer was extracted with CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, DCM:EtOAc:MeOH=65%:32%:3%) to afford the product as a yellow solid (175 mg). MS (ESI pos. ion) m/z: 550.0. 1H NMR (300 MHz, CDCl3) 8 ppm 1.41 (d, J=6.58 Hz, 3H) 2.34-2.48 (m, 2H) 2.49-2.60 (m, 2H) 2.66 (s, 3H) 2.81 (s, 3H) 3.13 (s, 3H) 3.39 (d, J=6.58 Hz, 1H) 3.72 (t, J=4.38 Hz, 4H) 6.75 (br. s., 1H) 7.45 (s, 1H) 8.01 (d, J=1.90 Hz, 1H) 8.30 (d, J=1.90 Hz, 1H) 8.52 (d, J=2.48 Hz, 1H) 8.76 (d, J=2.48 Hz, 1H) 12.43 (s, 1H).

Provenance & Evidence