反应详情

温度

50 °C

A microwave vial was charged with N-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (Intermediate II, 0.200 g, 0.353 mmol), 1-(2-bromo-5-(trifluoromethyl)phenyl)-4-methylpiperazine (Intermediate JJ, 0.228 g, 0.706 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.058 g, 0.071 mmol). Dioxane (1.765 ml) and t-BuOH (1.765 ml) were added, followed by sodium carbonate (2.0M in H2O) (0.530 ml, 1.059 mmol). The reaction was purged with nitrogen, and then heated at 50° C. overnight. After cooling to RT, the solids were filtered through a frit and washed with ethyl acetate. The filtrate was then washed with brine, and the organics were dried over magnesium sulfate, filtered and concentrated to yield a dark oil. Before deprotection, the material was dissolved in methanol and purified further with a strong cation exchange-column (SCX) (product eluted with the methanol/ammonia wash). After concentration, the material was diluted with DCM (1.0 mL) and TFA was added (1.0 mL). The reaction was stirred for 30 minutes at which time the reaction was concentrated under a vacuum. The material was purified via reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min to provide 5-(2-(4-methylpiperazin-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate (0.064 g, 0.099 mmol, 28.0% yield) as a tan glass. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.98-2.17 (m, 1H) 2.23-2.42 (m, 1H) 2.76-2.95 (m, 2H) 3.00-3.15 (m, 4H) 3.17 (s, 3H) 6.85 (d, J=4.60 Hz, 1H) 7.27 (d, J=4.60 Hz, 1H) 7.45-7.57 (m, 3H) 7.65-7.82 (m, 4H) 8.25 (d, J=7.63 Hz, 1H) 8.55 (d, J=1.86 Hz, 1H) 9.61 (br. s., 1H) 12.81 (br. s., 1H). m/z (ESI) 533.0 (M+H)+.

1. customThe reaction was purged with nitrogen
2. temperatureAfter cooling to RT
3. filtrationthe solids were filtered through a frit
4. washwashed with ethyl acetate
5. washThe filtrate was then washed with brine
6. dry with materialthe organics were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customto yield a dark oil
10. custompurified further with a strong cation exchange-column (SCX) (product
11. washeluted with the methanol/ammonia
12. washwash)
13. concentrationAfter concentration
14. additionthe material was diluted with DCM (1.0 mL) and TFA
15. additionwas added (1.0 mL)
16. concentrationwas concentrated under a vacuum
17. customThe material was purified via reverse-phase preparative HPLC
18. customover 20 min