Tetrabutylammonium Fluoride → 2-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246341Notes

Reaction equation

HRID 246341 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([C:26](C)(C)[O:27][SiH2]C(C)(C)C)[CH:24]=4)[N:19]([CH3:35])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([CH2:26][OH:27])[CH:24]=4)[N:19]([CH3:35])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131731223N-tert-butyl-2-[5-(2-tert-butylsilyloxypropan-2-yl)-1-methylindazol-3-yl]-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712794532-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[5-(tert-butyl-dimethyl-silanyloxymethyl)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (106 mg, 0.17 mmol) in THF (2 mL) was added tetrabutylammonium fluoride (1.0 M in THF, 1.7 mL, 1.7 mmol). The reaction mixture was stirred at room temperature for 10 min then heated at reflux for 2 h. After cooling to room temperature, the reaction was quenched with water and extracted with EtOAc and then with 5% MeOH/CH2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The residue was triturated with EtOAc/MeOH and the solids collected via filtration to afford 30 mg (47%) of 2-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid.

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 2 h
  3. temperatureAfter cooling to room temperature
  4. customthe reaction was quenched with water
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was triturated with EtOAc/MeOH
  9. filtrationthe solids collected via filtration

Sources & evidence

ORD record
ord-c63e7028e711420e80550f070b501587
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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