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

HRID 1026319Notes

Reaction equation

HRID 1026319 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]#[C:11][C:12]2[CH:29]=[CH:28][C:15]([O:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])=[CH:14][CH:13]=2)=[N:8][CH:9]=1)[CH3:2].[NH2:30]OS(C1C(C)=CC(C)=CC=1C)(=O)=O>C1COCC1>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([N:30]=[C:11]([C:12]3[CH:29]=[CH:28][C:15]([O:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])[CH3:19])=[CH:14][CH:13]=3)[CH:10]=2)[CH:9]=1)[CH3:2]

Participants

4

Reactant 2

HCID 11830845O-(2,4,6-Trimethylbenzenesulfonyl)hydroxylamineHCID 86666307tert-butyl [(1S)-2-{4-[(5-ethoxypyridin-2-yl)ethynyl]phenoxy}-1-methylethyl]carbamate

Product 1

HCID 86666306tert-butyl {(1S)-2-[4-(6-ethoxypyrazolo[1,5-a]pyridin-2-yl)phenoxy]-1-methylethyl}carbamateYield 50.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl [(1S)-2-{4-[(5-ethoxypyridin-2-yl)ethynyl]phenoxy}-1-methylethyl]carbamate (2.25 g) in THF (30 mL) was added 2-[(aminooxy)sulfonyl]-1,3,5-trimethylbenzene (1.75 g, containing water) at room temperature, and the mixture was stirred for 1 hr, and concentrated under reduced pressure. To the residue were added DMF (20 mL) and potassium carbonate (1.18 g), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and 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 colorless crystals (1.18 g).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionTo the residue were added DMF (20 mL) and potassium carbonate (1.18 g)
  3. stirringthe mixture was stirred at room temperature for 2 hr
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionthe residue was diluted with ethyl acetate and water
  6. customthe aqueous layer was separated from the organic layer
  7. extractionThe separated aqueous layer was extracted again with ethyl acetate
  8. washThe combined organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-11e485615a5f47d1a98a75caba6baa3c
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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