Ammonium Chloride → 3-Phenoxy-5-(pyridin-2-ylthio)pyridin-2-amine

HRID 1809574Notes

Reaction equation

HRID 1809574 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C[Li].C([Li])CCC.N1C=CC=C(S[S:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)C=1.[NH4+].[Cl-]>CO.C(Cl)Cl.C1COCC1>[O:9]([C:4]1[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([S:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH:3]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 459261405-Bromo-3-phenoxypyridin-2-amineHCID 866410882-(2-(Pyridin-3-yl)disulfanyl)pyridineHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 669951573-Phenoxy-5-(pyridin-2-ylthio)pyridin-2-amineYield 249.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A nitrogen purged flask was charged with 5-bromo-3-phenoxypyridin-2-amine (5.00 g, 18.9 mmol) and THF (80 mL) and cooled to −78° C. Methyllithium (14.1 mL, 22.6 mmol) was added and stirred for 5 minutes. Butyllithium (9.05 mL, 22.6 mmol) was added and the reaction was stirred for 10 minutes at −78° C. (solids precipitated). 2-(2-(Pyridin-3-yl)disulfanyl)pyridine (10.4 g, 47.2 mmol) was added and the reaction was warmed to ambient temperature and stirred for 18 hours. The reaction was poured into saturated aqueous NH4Cl and extracted with EtOAc, dried over sodium sulfate, filtered and concentrated. The residue was dissolved in methanol and NaBH4 (excess) was added and stirred for 10 minutes. The reaction was poured into saturated aqueous NH4Cl and extracted with EtOAc (2×75 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica (100% EtOAc to 1% methanol in EtOAc) to afford crude product. The material was dissolved in 2% MeOH in CH2Cl2 and washed with 1N NaOH. The organic layer was separated, dried, filtered, and concentrated to give 3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-amine (10.4 g, 47.2 mmol).

Workup

  1. stirringthe reaction was stirred for 10 minutes at −78° C.
  2. custom(solids precipitated)
  3. temperaturethe reaction was warmed to ambient temperature
  4. stirringstirred for 18 hours
  5. extractionextracted with EtOAc
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in methanol
  10. additionNaBH4 (excess) was added
  11. stirringstirred for 10 minutes
  12. additionThe reaction was poured into saturated aqueous NH4Cl
  13. extractionextracted with EtOAc (2×75 mL)
  14. dry with materialThe organic layer was dried with sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe residue was purified on silica (100% EtOAc to 1% methanol in EtOAc)
  18. customto afford crude product
  19. washwashed with 1N NaOH
  20. customThe organic layer was separated
  21. customdried
  22. filtrationfiltered
  23. concentrationconcentrated

Sources & evidence

ORD record
ord-54fea51efaf2448eac3d994f36f30eb3
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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