Thionyl Chloride → HCID 10322698, compound

HRID 1760570Notes

Reaction equation

HRID 1760570 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](O)([C:27]2[N:28]([CH3:32])[CH:29]=[N:30][CH:31]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]3[C:21]2[S:22][C:23]([CH3:26])=[CH:24][CH:25]=2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.CO.C(Cl)(Cl)Cl.[NH4+:44].[OH-]>C1(C)C=CC=CC=1>[NH2:44][C:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([C:27]1[N:28]([CH3:32])[CH:29]=[N:30][CH:31]=1)[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]2[C:21]1[S:22][C:23]([CH3:26])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 10050637HCID 10050637, compoundHCID 21873181Chloroform methanol ammonium hydroxide

Product 1

HCID 10322698HCID 10322698, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-4-(5-methyl-thiophen-2-yl)-1H-quinolin-2-one (63 mg, 0.132 mmol) in toluene (1 ml) was added thionyl chloride (SOCl2, 0.097 ml, 1.32 mmol). The reaction mixture was heated to reflux for 2 hours. Thiony chloride was removed under reduced pressure. The crude chloride was taken up in toluene and concentrated under vacuum. The resulting solid was dissolved in THF (5 mL) and to this solution was bubbled ammonia gas (NH3) for 10 minutes at −78° C. The excess NH3 was removed via bubble N2 at −30° C. After removal of THF, the product mixture was partitioned between ethyl acetate and 10% aqueous potassium carbonate. The organic layer was washed, dried over MgSO4 and concentrated under vacuum to give the crude product. It was chromatographed on silica gel with CHCl3 then MeOH—CHCl3—NH4OH (1:99:0.1) as eluents to afford the titled compound as an off-white solid (31 mg, 0.065 mmol, 49% yield).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThiony chloride was removed under reduced pressure
  4. concentrationconcentrated under vacuum
  5. dissolutionThe resulting solid was dissolved in THF (5 mL) and to this solution
  6. customwas bubbled ammonia gas (NH3) for 10 minutes at −78° C
  7. customThe excess NH3 was removed
  8. customvia bubble N2 at −30° C
  9. customAfter removal of THF
  10. customthe product mixture was partitioned between ethyl acetate and 10% aqueous potassium carbonate
  11. washThe organic layer was washed
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated under vacuum
  14. customto give the crude product
  15. customIt was chromatographed on silica gel with CHCl3

Sources & evidence

ORD record
ord-c5c2821aa87c4598878f8942094112c5
Source dataset
uspto-grants-2005_01
Patent number
US06844357B2

Reaction notes

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