反应详情

To a stirred solution of N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (Example 384, Step 2, 0.0697 g, 0.278 mmol) and 4-(2-fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 330, Step 5, 0.0595 g, 0.253 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 1.02 mL, 1.02 mmol) was added dropwise at 0° C. The dark red solution was stirred at that temperature for 45 min. Sat'd NH4Cl (0.2 mL) was added to quench the reaction. The reaction mixture was poured into sat'd NH4Cl (20 mL) and the mixture was stirred for 5 min. The resulting brown precitipate was collected and the crude product was purified by preparative HPLC using a Phenomenex, Gemni 5 micron C18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The corresponding fractions were collected and concentrated in vacuo. The residue was collected and washed with water and small amount of MeOH to afford N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxy-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (0.0240 g, 20% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.00 (br. s., 1H) 9.53 (br. s., 1H) 8.77 (br. s., 1H) 8.52 (br. s., 1H) 8.35-8.46 (m, 1H) 8.19 (br. s., 1H) 7.71-8.03 (m, 2H) 3.86 (br. s., 3H) 2.79 (br. s., 6H) 2.46 (br. s., 3H). m/z (ESI, positive ion) m/z: 466.0 (M+H)+.

1. customto quench
2. customthe reaction
3. stirringthe mixture was stirred for 5 min
4. customThe resulting brown precitipate was collected
5. customthe crude product was purified by preparative HPLC
6. customC18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
7. customThe corresponding fractions were collected
8. concentrationconcentrated in vacuo
9. customThe residue was collected
10. washwashed with water and small amount of MeOH