Sodium bis(trimethylsilyl)amide → N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

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To a stirred solution of 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 384, Step 2, 0.0614 g, 0.202 mmol) and N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (KY, 0.050 g, 0.199 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 0.80 mL, 0.80 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 45 min. The reaction mixture was partitioned between saturated aqueous ammonium chloride (30 mL) and 25% isopropanol in chloroform (20 mL). The aqueous phase was acidified to a pH of about 3 to 4 then extracted with 25% isopropanol in chloroform (2×30 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (25 g, eluent: iPrOH in CHCl3 0%-25%) to afford N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (0.0437 g, 44% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.28 (s, 1H) 9.57 (s, 1H) 8.82 (s, 1H) 8.76 (d, J=2.35 Hz, 1H) 8.53 (d, J=2.35 Hz, 1H) 8.29 (d, J=2.35 Hz, 1H) 7.74-7.98 (m, 2H) 3.57 (t, J=4.21 Hz, 4H) 3.48 (s, 2H) 2.79 (s, 6H) 2.46 (s, 3H) 2.35-2.43 (m, 4H). m/z (ESI, positive ion): 535.0 (M+H)+.

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