Bromine → Tert-butyl {4-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-3-fluorophenyl}carbamate

HRID 2095773Notes

Reaction equation

HRID 2095773 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:15][C:14]=2[F:27])=[N:10][CH:11]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:11]2[C:6]([N:5]=1)=[CH:7][CH:8]=[C:9]([O:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[CH:15][C:14]=1[F:27])[N:10]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 58158488Tert-butyl {4-[(5-aminopyridin-2-yl)oxy]-3-fluorophenyl}carbamate

Product 1

HCID 58158490Tert-butyl {4-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-3-fluorophenyl}carbamateYield 35%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

To a solution of potassium thiocyanate (6.1 g, 62.6 mmol) in acetic acid (60 mL) was added a solution of tert-butyl {4-[(5-aminopyridin-2-yl)oxy]-3-fluorophenyl}carbamate (5.0 g, 15.7 mmol) in acetic acid (40 mL) at 0° C. A solution of bromine (3.25 g, 20.4 mmol) in acetic acid (20 mL) was added at 0° C., and the mixture was stirred at room temperature for 6 hr. Acetic acid was evaporated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate alone) to give the title compound (2.07 g, 35%).

Workup

  1. customAcetic acid was evaporated under reduced pressure, saturated aqueous sodium hydrogen carbonate
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate alone)

Sources & evidence

ORD record
ord-c0c4792cb28749bdbe08672b8a92b421
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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