1,3-Dibromo-5,5-dimethylhydantoin → HCID 58318609, compound

HRID 473412Notes

Reaction equation

HRID 473412 reaction equation
[CH2:1]([C:3]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[N:4]=1)[CH3:2].BrN1C(C)(C)C(=O)N(Br)C1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(=O)(O)[O-].[Na+].BrC(C1C(C2C=CC=CC=2)=CC2C(=CC=CN=2)N=1)C.[K].[C:73]1(=[O:83])[NH:77][C:76](=[O:78])[C:75]2=[CH:79][CH:80]=[CH:81][CH:82]=[C:74]12>C(Cl)(Cl)(Cl)Cl.CN(C=O)C>[C:13]1([C:12]2[C:3]([CH:1]([N:77]3[C:73](=[O:83])[C:74]4[C:75](=[CH:79][CH:80]=[CH:81][CH:82]=4)[C:76]3=[O:78])[CH3:2])=[N:4][C:5]3[C:10]([CH:11]=2)=[N:9][CH:8]=[CH:7][CH:6]=3)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

9

Reactant 6

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 7187Benzoyl PeroxideHCID 516892Sodium BicarbonateHCID 24194345Phthalimide potassium saltHCID 58318634HCID 58318634, compoundHCID 58318635HCID 58318635, compound

Product 1

HCID 58318609HCID 58318609, compound

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Procedure

2-Ethyl-3-phenyl-1,5-naphthyridine (112 mg, 0.43 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (85 mg, 0.7 eq) were suspended in carbon tetrachloride (5 mL). To the mixture was added benzoyl peroxide (10.3 mg, 0.1 eq) and the mixture was heated at reflux for 3 h. To the mixture was added saturated aqueous sodium bicarbonate solution (3 mL). The layers were separated and the aqueous layer was extracted with CH2CH2 (3 mL×2). The combined organic layers were washed with brine (3 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give an orange syrup. The material is used as such for the next step. LC-MS (ESI) m/z 314 [M+H]+. A mixture of 2-(1-bromoethyl)-3-phenyl-1,5-naphthyridine (120 mg, 0.38 mmol) in DMF (2.0 mL) was treated with phthalimide potassium salt (142 mg, 2.0 eq) at 60° C. for 2 h. LCMS showed completion. The reaction mixture was partitioned between water and EtOAc, worked up and purified by silica gel column chromatography using EtOAc-hexane (0/1 to 2/1) as eluent to give a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.88 (1H, dd, J=5.0, 1.6 Hz), 8.31 (1H, J=10 Hz), 8.1 (1H, s), 7.63-7.54 (5H, m), 7.27-7.17 (8H, m), 5.88 (1H, dd, J=10, 5.0 Hz), 1.76 (3 H, J=10 Hz); LC-MS (ESI) m/z 380 [M+H]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2CH2 (3 mL×2)
  5. washThe combined organic layers were washed with brine (3 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give an orange syrup
  10. customThe reaction mixture was partitioned between water and EtOAc
  11. custompurified by silica gel column chromatography
  12. customto give a white solid

Sources & evidence

ORD record
ord-0b3df1e2c0c743389cbf54166d345b53
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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