Sodium bis(trimethylsilyl)amide → N-(5-((3-(6-amino-2-methyl-4-pyrimidinyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)methanesulfonamide

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide (Example 330, Step 2) (0.085 g, 0.384 mmol) in THF (5.0 mL) at 0° C. was added NaHMDS (2 M solution in THF) (0.959 mL, 1.918 mmol). After the addition, the reaction mixture continued to stir at 0° C. under N2 for 30 minutes. 6-(2-fluoro-3-pyridinyl)-2-methyl-4-pyrimidinamine (0.094 g, 0.460 mmol) was added into the reaction mixture and the reaction mixture continued to stir at 0° C. for 10 minutes and was then slowly warmed up at RT. After 1 hour at RT, more NaHMDS (2 M solution in THF) (0.50 mL, 1.0 mmol) was added. After 1 more hour, the reaction mixture was partitioned between pH 7 buffer (1 M TRIS-HCl) and CH2Cl2. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by HPLC to afford N-(5-((3-(6-amino-2-methyl-4-pyrimidinyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)methanesulfonamide (0.0190 g, 0.047 mmol, 12.20% yield). m/z (ESI, +ve) 406.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.68 (s, 1H); 9.66 (s, 1H); 8.61 (d, J=2.74 Hz, 1H); 8.41 (d, J=2.54 Hz, 1H); 8.32 (dd, J=4.89, 1.76 Hz, 1H); 8.10-8.14 (m, 1H); 7.09 (s, 2H); 7.02 (dd, J=7.82, 4.69 Hz, 1H); 6.78 (s, 1H); 3.13 (s, 3H); 2.52 (s, 3H).

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