Trifluoroacetic acid → 2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-6-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyrazine

HRID 1481548Notes

Reaction equation

HRID 1481548 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:22]CC2C=CC(OC)=CC=2)[C:5]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=O)=[N:6][CH:7]=1.[C:32](O)([C:34]([F:37])([F:36])[F:35])=O>>[C:17]([C:14]1[C:15]([Cl:16])=[C:11]([C:9]2[NH:22][C:4]3=[N:3][C:2]([C:18]4[CH:17]=[CH:14][CH:15]=[CH:11][C:32]=4[C:34]([F:37])([F:36])[F:35])=[CH:7][N:6]=[C:5]3[N:8]=2)[N:12]([CH3:21])[N:13]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866574125-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [5-bromo-3-(4-methoxy-benzylamino)-pyrazin-2-yl]-amide

Product 1

HCID 1360731772-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-6-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyrazine

Conditions

Temperature
65 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5f14e08d74db4515af5a9b9b7d9a922f
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

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