1,3-Dichloro-5,5-dimethylhydantoin → HCID 86687720, compound

HRID 1473649Notes

Reaction equation

HRID 1473649 reaction equation
C(SC1C=C2C(C(C3C=CC=CC=3OC)=NNC2=O)=CC=1)C1C=CC=CC=1.ClN1C(C)(C)C(=O)N(Cl)C1=O.S(Cl)(Cl)(=O)=O.[Cl:44][C:45]1[CH:46]=[CH:47][C:48]([O:66][CH3:67])=[C:49]([C:51]2[C:60]3[C:55](=[CH:56][C:57]([S:61](Cl)(=[O:63])=[O:62])=[CH:58][CH:59]=3)[C:54](=[O:65])[NH:53][N:52]=2)[CH:50]=1.[F:68][C:69]1[C:74]([F:75])=[C:73]([F:76])[C:72]([F:77])=[C:71]([F:78])[C:70]=1[OH:79].C(N(CC)CC)C>CCOC(C)=O.C(Cl)Cl.O.C(O)(=O)C.C(#N)C>[Cl:44][C:45]1[CH:46]=[CH:47][C:48]([O:66][CH3:67])=[C:49]([C:51]2[C:60]3[C:55](=[CH:56][C:57]([S:61]([O:79][C:70]4[C:71]([F:78])=[C:72]([F:77])[C:73]([F:76])=[C:74]([F:75])[C:69]=4[F:68])(=[O:63])=[O:62])=[CH:58][CH:59]=3)[C:54](=[O:65])[NH:53][N:52]=2)[CH:50]=1

Participants

12

Reactant 6

HCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 8471TriethylamineHCID 13041PentafluorophenolHCID 24648Sulfuryl chlorideHCID 86687721HCID 86687721, compoundHCID 86687722HCID 86687722, compound

Product 1

HCID 86687720HCID 86687720, compoundYield 60%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A round-bottom flask was charged with 7-(benzylthio)-4-(2-methoxyphenyl)phthalazin-1(2H)-one (150 mg, 0.401 mmol), acetonitrile (3770 μl), acetic Acid (141 μl), and water (94 μl) to give a yellow suspension. The mixture was sonicated to give a yellow suspension. The flask was cooled in an ice-bath for 30 min, then 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (158 mg, 0.801 mmol) was added in one portion. After 20 min, LCMS showed SM (m/z=375), sulfoxide (m/z=391), sulfonyl chloride (m/z=352), Cl-sulfonyl chloride (m/z=385,387). DCM (0.5 mL) was added to give a yellow solution. After 1.5 h, an orange suspension was formed. LCMS showed mainly 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonyl chloride. Then, 2,3,4,5,6-pentafluorophenol (147 mg, 0.801 mmol) was added at 0° C., followed by drop wise addition of triethylamine (223 μl, 1.602 mmol) via an addition funnel. After 15 min, LCMS showed mainly PFP sulfonate product. The mixture was diluted with EtOAc (20 mL) and washed with water (2×10 mL), washed with brine, and dried over sodium sulfate. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in hexanes, to provide perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (128 mg, 60.0% yield) as white solid. HMBC connectivities and ROESY cross-peaks confirmed the structure of perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (128 mg, 60% yield). Specifically, the chlorine was para to the methoxy substitutent. m/z (ESI) 533.0 (M+H)+.

Workup

  1. customto give a yellow suspension
  2. customThe mixture was sonicated
  3. customto give a yellow suspension
  4. temperatureThe flask was cooled in an ice-bath for 30 min
  5. customto give a yellow solution
  6. waitAfter 1.5 h
  7. customan orange suspension was formed
  8. waitAfter 15 min
  9. washwashed with water (2×10 mL)
  10. washwashed with brine
  11. dry with materialdried over sodium sulfate
  12. customThe crude material was absorbed onto a plug of silica gel
  13. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  14. washeluting with a gradient of 0% to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-1ee1a17248b34eb0aba4f37a20d38b05
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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