Sodium bis(trimethylsilyl)amide → N'-(2-chloro-5-((3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-(4-morpholinyl)ethyl)-2-pyridinyl)amino)-3-pyridinyl)-N,N-dimethylsulfamide

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To a stirred solution of 4-(1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)morpholine (Example 339 step 4, 0.0475 g, 0.111 mmol) and N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (Example 384, Step 2 0.0380 g, 0.152 mmol) in THF (1 mL) in 20 mL scintillation vial, NaHMDS (Aldrich, 1 M in THF, 0.445 mL, 0.445 mmol) was added dropwise at 0° C. The dark red mixture was stirred at 0° C. for 30 min. The reaction mixture was partitioned between buffer (pH 5.0, citric acid/NaOH) (20 mL) and EtOAc (20 mL) resulted in having insoluble materials. The biphase mixture was filtered and the solid was collected and washed with water to afford N′-(2-chloro-5-((3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-(4-morpholinyl)ethyl)-2-pyridinyl)amino)-3-pyridinyl)-N,N-dimethylsulfamide (0.0472 g, 65% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 13.12 (s, 1H) 9.76 (s, 1H) 8.86 (d, J=2.35 Hz, 1H) 8.50 (d, J=1.96 Hz, 1H) 8.32 (s, 2H) 6.79 (br. s., 1H) 5.87 (d, J=8.22 Hz, 1H) 4.16-4.26 (m, 1H) 3.79-3.90 (m, 1H) 3.73 (br. s., 4H) 3.55 (br. s., 1H) 2.87-3.04 (m, 9H) 2.50 (br. s., 4H) 1.98-2.21 (m, 3H) 1.69-1.92 (m, 3H) 1.48 (d, J=6.46 Hz, 3H). m/z (ESI, positive ion): 657.0 (M+H)+.

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