hydroxylamine-O-sulfonic acid → tert-butyl [(1S)-2-{4-[6-(cyclopropylmethoxy)pyrazolo[1,5-a]pyridin-2-yl]phenoxy}-1-methylethyl]carbamate

HRID 1026317Notes

Reaction equation

HRID 1026317 reaction equation
[NH2:1]OS(=O)(=O)O.C(=O)([O-])O.[Na+].[CH:12]1([CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]3[CH:42]=[CH:41][C:28]([O:29][CH2:30][C@@H:31]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH3:32])=[CH:27][CH:26]=3)=[N:21][CH:22]=2)[CH2:14][CH2:13]1>O.CO>[CH:12]1([CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[N:21]([N:1]=[C:24]([C:25]4[CH:42]=[CH:41][C:28]([O:29][CH2:30][C@@H:31]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])[CH3:32])=[CH:27][CH:26]=4)[CH:23]=3)[CH:22]=2)[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 76284hydroxylamine-O-sulfonic acidHCID 516892Sodium BicarbonateHCID 86666303tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamate

Product 1

HCID 86666305tert-butyl [(1S)-2-{4-[6-(cyclopropylmethoxy)pyrazolo[1,5-a]pyridin-2-yl]phenoxy}-1-methylethyl]carbamateYield 15.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

(Aminooxy)(hydroxy)sulfane dioxide (679 mg) was dissolved in water (3 mL), and saturated aqueous sodium hydrogen carbonate solution was added dropwise thereto at 0° C. to neutralize the solution. To the obtained mixture was added a solution of tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamate (845 mg) in methanol (5 mL) at room temperature, and the mixture was stirred at 60° C. overnight, and concentrated under reduced pressure. To the residue were added DMF (8 mL) and potassium carbonate (829 mg), and the mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate and water, and the aqueous layer was separated from the organic layer. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a colorless solid (134 mg).

Workup

  1. customat 0° C.
  2. concentrationconcentrated under reduced pressure
  3. additionTo the residue were added DMF (8 mL) and potassium carbonate (829 mg)
  4. stirringthe mixture was stirred at room temperature for 4 hr
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionthe residue was diluted with ethyl acetate and water
  7. customthe aqueous layer was separated from the organic layer
  8. extractionThe separated aqueous layer was extracted again with ethyl acetate
  9. washThe combined organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a6248265b87849a2aef1ac3f54dbd461
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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