Hydrochloric Acid → 7-Mercapto-2-isopropyl-4-bromo-2H-phthalazin-1-one

HRID 1783715Notes

Reaction equation

HRID 1783715 reaction equation
S(=O)(=O)(O)O.N[C:7]1[CH:16]=[C:15]2[C:10]([C:11]([Br:21])=[N:12][N:13]([CH:18]([CH3:20])[CH3:19])[C:14]2=[O:17])=[CH:9][CH:8]=1.N([O-])=O.[Na+].NC(N)=O.O(CC)C([S-])=[S:32].[K+].[OH-].[Na+].Cl>CC(O)=O.O.C(Cl)Cl>[SH:32][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([Br:21])=[N:12][N:13]([CH:18]([CH3:20])[CH3:19])[C:14]2=[O:17])=[CH:9][CH:8]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 1176UreaHCID 14798Sodium HydroxideHCID 2735045Potassium ethylxanthateHCID 211065807-Amino-2-Isopropyl-4-bromo-2H-phthalazin-1-oneHCID 23668193Sodium Nitrite

Product 1

HCID 1363729987-Mercapto-2-isopropyl-4-bromo-2H-phthalazin-1-oneYield 48.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Concentrated sulfuric acid (5 ml) was added dropwise to a solution of 7-amino-2-isopropyl-4-bromo-2H-phthalazin-1-one (1.5 g, 5.3 mmol) in HOAc (15 ml) and the solution was cooled to 0° C. A solution of sodium nitrite (0.5 g, 7.4 mmol) in water (2.5 ml) was added dropwise and the reaction mixture was stirred at 0° C. for 20 min, after which time urea (0.17 g, 2.8 mmol) was added in one portion. The reaction mixture was then added dropwise to a solution of potassium ethyl xanthate (6 g, 37.7 mmol) in water (7.5 ml) and the mixture was heated to 80° C. for 30 min. After this time, the reaction mixture was cooled to RT and DCM (100 ml) was added. The organic layer was separated, dried (MgSO4), filtered and concentrated under vacuum. The residue was taken up in THF (10 ml), NaOH (4.95 g, 0.12 mmol) was added in one portion and the mixture was heated to reflux for 24 hours. The mixture was then cooled to RT and the suspension was acidified to pH 2 with concentrated HCl. DCM (100 ml) was added, the organic layer was separated and was subsequently washed with HCl (1M, 20 ml) and water (20 ml). The organic layer was extracted with NaOH (1M, 200 ml), the aqueous layer was separated and acidified to pH 1 with concentrated HCl. The mixture was extracted with DCM (2×50 ml), the organic layers were combined, dried (MgSO4), filtered and concentrated under vacuum to give the title compound (0.77 g, 48% yield) as a light brown solid which was taken on directly without further purification.

Workup

  1. temperaturethe mixture was heated to 80° C. for 30 min
  2. temperatureAfter this time, the reaction mixture was cooled to RT
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. temperaturethe mixture was heated
  8. temperatureto reflux for 24 hours
  9. temperatureThe mixture was then cooled to RT
  10. customthe organic layer was separated
  11. washwas subsequently washed with HCl (1M, 20 ml) and water (20 ml)
  12. extractionThe organic layer was extracted with NaOH (1M, 200 ml)
  13. customthe aqueous layer was separated
  14. extractionThe mixture was extracted with DCM (2×50 ml)
  15. dry with materialdried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-125e173b9c06410c8c1d292b9a52e61f
Source dataset
uspto-grants-2009_03
Patent number
US07501410B2

Reaction notes

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