N-Iodosuccinimide → 4-[(R)-1-(3,5-Dichloro-4-fluoro-phenyl)-5-iodo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile

HRID 1040519Notes

Reaction equation

HRID 1040519 reaction equation
[Al].[Cl:2][C:3]1[CH:4]=[C:5]([N:11]2[C:15](=[O:16])[C@:14]([CH2:18][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)([CH3:17])[N:13]3[CH:27]=[CH:28][N:29]=[C:12]23)[CH:6]=[C:7]([Cl:10])[C:8]=1[F:9].[I:30]N1C(=O)CCC1=O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[Cl:2][C:3]1[CH:4]=[C:5]([N:11]2[C:15](=[O:16])[C@:14]([CH2:18][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)([CH3:17])[N:13]3[C:27]([I:30])=[CH:28][N:29]=[C:12]23)[CH:6]=[C:7]([Cl:10])[C:8]=1[F:9]

Participants

6

Reactant 4

HCID 120273N-IodosuccinimideHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 5359268AluminumHCID 584311004-[(R)-1-(3,5-Dichloro-4-fluoro-phenyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile

Product 1

HCID 584308774-[(R)-1-(3,5-Dichloro-4-fluoro-phenyl)-5-iodo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrileYield 81.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

An aluminum foil covered flask containing a solution of 4-[(R)-1-(3,5-dichloro-4-fluoro-phenyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile (48.8 g, 117.5 mmol) in CH2Cl2 (900 mL) was partially submerged in an ice water bath. To this solution was added a solid mixture of N-iodosuccinimide (29.1 g, 129 mmol) and pyridinium p-toluenesulfonate (2.95 g, 11.7 mmol) in four separate portions over a 30 min period. The reaction was allowed to stir in the thawing ice bath for 1 h and then the bath was removed. Stirring was continued overnight. Saturated aqueous Na2S2O3 (300 mL) was added to the reaction and the mixture was transferred to a separatory funnel using CH2Cl2 (200 mL) and water (1 L). The layers were separated and the aqueous layer was further extracted with CH2Cl2 (2×500 mL) and EtOAc (500 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give a yellow oil. This oil was purified by flash chromatography on silica gel (0-2.5% EtOAc/toluene) to give 52 g of the title compound as a white solid, m/z 541.3 [M+H]+.

Workup

  1. customwas partially submerged in an ice water bath
  2. additionTo this solution was added
  3. customseparate portions over a 30 min period
  4. customthe bath was removed
  5. stirringStirring
  6. waitwas continued overnight
  7. additionSaturated aqueous Na2S2O3 (300 mL) was added to the reaction
  8. customthe mixture was transferred to a separatory funnel
  9. customThe layers were separated
  10. extractionthe aqueous layer was further extracted with CH2Cl2 (2×500 mL) and EtOAc (500 mL)
  11. dry with materialThe combined organic layers were dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customto give a yellow oil
  14. customThis oil was purified by flash chromatography on silica gel (0-2.5% EtOAc/toluene)

Sources & evidence

ORD record
ord-786f0239ceb54c45a8910cf9da3f9bd4
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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