4-Amino-3-fluoropyridine → {1-[2-Bromo-4-(3-fluoro-pyridin-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 2409368Notes

Reaction equation

HRID 2409368 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH3:12])[C:5]([OH:7])=O.[F:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:27]=1[NH2:28]>C1COCC1>[C:17]([O:16][C:14](=[O:15])[NH:13][CH:11]([C:10]1[CH:9]=[CH:8][C:4]([C:5](=[O:7])[NH:28][C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[F:21])=[CH:3][C:2]=1[Br:1])[CH3:12])([CH3:20])([CH3:19])[CH3:18]

Participants

4

Reactant 2

HCID 8171224-Amino-3-fluoropyridineHCID 674090933-Bromo-4-(1-tert-butoxycarbonylamino-ethyl)-benzoic acid

Product 1

HCID 67407943{1-[2-Bromo-4-(3-fluoro-pyridin-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-bromo-4-(1-tert-butoxycarbonylamino-ethyl)-benzoic acid (8352 μmol) in dry THF (20 ml) was added Ghosez reagent (2 eq.). The mixture was stirred at RT for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in dry pyridine (20 ml) and 3-fluoro-pyridin-4-ylamine (1.2 eq) was added. The reaction mixture was stirred at RT for 2.5 hours. The pyridine was removed under reduced pressure. The residue was dissolved in 1N Na2CO3 and extracted with EtOAc. The combined organic layers were washed with 1N NaHCO3, citric acid and water. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The compound was purified by column chromatography (silicagel, DCM/MeOH gradient).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in dry pyridine (20 ml)
  3. stirringThe reaction mixture was stirred at RT for 2.5 hours
  4. customThe pyridine was removed under reduced pressure
  5. dissolutionThe residue was dissolved in 1N Na2CO3
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with 1N NaHCO3, citric acid and water
  8. dry with materialThe organic layer was dried over MgSO4
  9. customthe solvent was removed under reduced pressure
  10. customThe compound was purified by column chromatography (silicagel, DCM/MeOH gradient)

Sources & evidence

ORD record
ord-5a34995ec1de4ebbb4b62fde4446f434
Source dataset
uspto-grants-2014_08
Patent number
US08815873B2

Reaction notes

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