Tetrabutylammonium Fluoride → tert-butyl 5-ethynyl-3-(pyridin-4-yl)-1H-indazole-1-carboxylate

HRID 1465692Notes

Reaction equation

HRID 1465692 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[C:17][Si](C(C)C)(C(C)C)C(C)C)[CH:14]=3)[N:9]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:8]=2)=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:16]([C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:8]=[C:7]2[C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)#[CH:17]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67517348tert-butyl 3-(pyridin-4-yl)-5-((triisopropylsilyl)ethynyl)-1H-indazole-1-carboxylate

Product 1

HCID 86695574tert-butyl 5-ethynyl-3-(pyridin-4-yl)-1H-indazole-1-carboxylateYield 37.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 3-(pyridin-4-yl)-5-((triisopropylsilyl)ethynyl)-1H-indazole-1-carboxylate (3.10 g, 6.5 mmol) in THF (100 ml) was added 1M TBAF in THF (7.2 ml, 7.2 mmol). The reaction was stirred for 3 h at room temperature. Upon completion, the reaction mixture was quenched with the addition of saturated aqueous NH4Cl (50 ml) and extracted with Et2O (3×100 ml). The combined organic extracts were washed with saturated aqueous NaCl (100 ml) and dried with anhydrous Na2SO4. The organic phase was concentrated under reduced pressure and column purified (20-80% EtAOc/Hexane) to give the desired product of tert-butyl 5-ethynyl-3-(pyridin-4-yl)-1H-indazole-1-carboxylate (0.77 g) and the de-Boc product of 5-ethynyl-3-(pyridin-4-yl)-1H-indazole (0.40 g).

Workup

  1. customUpon completion, the reaction mixture was quenched with the addition of saturated aqueous NH4Cl (50 ml)
  2. extractionextracted with Et2O (3×100 ml)
  3. washThe combined organic extracts were washed with saturated aqueous NaCl (100 ml)
  4. dry with materialdried with anhydrous Na2SO4
  5. concentrationThe organic phase was concentrated under reduced pressure and column
  6. custompurified (20-80% EtAOc/Hexane)

Sources & evidence

ORD record
ord-8d3c662ad0334b3b9d26e22c92a90df6
Source dataset
uspto-grants-2015_04
Patent number
US08999966B2

Reaction notes

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