Trifluoroacetic acid → 2-(6-chloro-1-((5-methylisoxazol-3-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246456Notes

Reaction equation

HRID 246456 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]3[N:19]=[C:20]4[C:26]([C:27]([NH:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:25][N:24](COCC[Si](C)(C)C)[C:21]4=[N:22][CH:23]=3)=[N:7][N:8]2[CH2:11][C:12]2[CH:16]=[C:15]([CH3:17])[O:14][N:13]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.ClCCl.CO>ClCCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]3[N:19]=[C:20]4[C:26]([C:27]([NH:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:25][NH:24][C:21]4=[N:22][CH:23]=3)=[N:7][N:8]2[CH2:11][C:12]2[CH:16]=[C:15]([CH3:17])[O:14][N:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 21226129Dichloromethane methanolHCID 712799782-(6-chloro-1-((5-methylisoxazol-3-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712802072-(6-chloro-1-((5-methylisoxazol-3-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 22%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

2-(6-Chloro-1-((5-methylisoxazol-3-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (89 mg, 153 μmol) was dissolved in 1,2-dichloroethane (3 mL) and placed in a sealed tube. To this was added trifluoroacetic acid (1.75 g, 1.18 mL, 15.3 mmol). The tube was sealed and the mixture heated at to 80° C. After 15 h, the mixture was cooled and concentrated in vacuo. The residue was purified by chromatography (silica, 24 g Analogix column, 95:5 dichloromethane:methanol) then preparative TLC (95:5 dichloromethane/methanol) to give 2-(6-chloro-1-((5-methylisoxazol-3-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (15 mg, 33.3 μmol, 22%). MS (M+Na)+=472; 1H NMR (CDCl3) δ: 9.37 (s, 1H), 9.22-9.32 (m, 1H), 8.42-8.51 (m, 1H), 8.34-8.40 (m, 1H), 8.11-8.21 (m, 1H), 7.56-7.63 (m, 1H), 7.19-7.36 (m, 1H), 5.90-5.97 (m, 1H), 5.63-5.75 (m, 2H), 4.38-4.56 (m, 1H), 2.38 (s, 3H), 1.41 (d, J=6.4 Hz, 6H).

Workup

  1. customplaced in a sealed tube
  2. customThe tube was sealed
  3. temperaturethe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography (silica, 24 g Analogix column, 95:5 dichloromethane:methanol)

Sources & evidence

ORD record
ord-1c53af43d14b40c1b784890630fc3ac8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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