反应详情

温度

65 °C

A solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [5-bromo-3-(4-methoxy-benzylamino)-pyrazin-2-yl]-amide (28 mg, 0.04 mmol, prepared as described in the previous step) in TFA (3.5 mL) was stirred at 65° C. for 3 h. The resulting mixture was allowed to cool to room temperature, TFA was removed in vacuo and the resulting residue was dissolved in EtOAc (10 mL) and washed with saturated NaHCO3 (20 mL). EtOAc layer was separated, dried (Na2SO4), and concentrated in vacuo. The resulting residue was dissolved in HOAc (3.5 mL) and stirred at 100° C. overnight. The resulting mixture was allowed to cool to room temperature and the HOAc was removed in vacuo. The resulting residue was dissolved in EtOAc (10 mL) and washed with saturated NaHCO3 (10 mL). EtOAc layer was separated, dried (Na2SO4), and concentrated in vacuo. The resulting residue was purified on silica 0:100-50:50 EtOAc-hexane to yield 2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-6-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyrazine. 1H-NMR (CD3OD) δ: 8.53-8.57 (br s, 1H), 7.82-7.86 (m, 1H), 7.68-7.74 (m, 1H), 7.61-7.67 (m, 1H), 7.57-7.60 (m, 1H), 4.19 (s, 3H), 1.43 (s, 9H). Mass Spectrum (LCMS, ESI pos.): Calculated for C20H18ClF3N6: 435.1 (M+H); Measured: 435.1.

1. temperatureto cool to room temperature
2. customTFA was removed in vacuo
3. dissolutionthe resulting residue was dissolved in EtOAc (10 mL)
4. washwashed with saturated NaHCO3 (20 mL)
5. customEtOAc layer was separated
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. dissolutionThe resulting residue was dissolved in HOAc (3.5 mL)
9. stirringstirred at 100° C. overnight
10. temperatureto cool to room temperature
11. customthe HOAc was removed in vacuo
12. dissolutionThe resulting residue was dissolved in EtOAc (10 mL)
13. washwashed with saturated NaHCO3 (10 mL)
14. customEtOAc layer was separated
15. dry with materialdried (Na2SO4)
16. concentrationconcentrated in vacuo
17. customThe resulting residue was purified on silica 0:100-50:50 EtOAc-hexane