Ammonium Chloride → HCID 11340754, compound

HRID 2252024Notes

Reaction equation

HRID 2252024 reaction equation
C([Mg]Cl)(C)C.[CH:6]([S:9]([N:12]1[C:16]2[CH:17]=[C:18](I)[CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH2:22])(=[O:11])=[O:10])([CH3:8])[CH3:7].CN(OC)[C:25](=[O:41])[CH:26]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Cl-].[NH4+]>O1CCCC1>[CH:6]([S:9]([N:12]1[C:16]2[CH:17]=[C:18]([C:25](=[O:41])[CH:26]([O:33][Si:34]([C:37]([CH3:39])([CH3:38])[CH3:40])([CH3:36])[CH3:35])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH2:22])(=[O:11])=[O:10])([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 106425631-Isopropylsulfonyl-2-amino-6-iodobenzimidazoleHCID 85449068HCID 85449068, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 11340754HCID 11340754, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Add isopropylmagnesium chloride (2.0 M in THF, 235 mL, 470 mmol) over 15 minutes to a solution of 1-isopropylsulfonyl-2-amino-6-iodobenzimidazole (42.9 g, 118 mmol) in tetrahydrofuran (850 mL) at −70° C. under a nitrogen atmosphere. Stir for 1 hour at 0° C. and then add a solution of N-[methyl] N-[methoxy] 2-(tert-butyldimethylsilyl)oxy-2-(phenyl)acetamide (90.0 g, 294 mmol) (Tius, et al., Tetrahedron, 56, 3339-3351-(2000)) in tetrahydrofuran (150 mL) via cannula. Stir the resulting slurry at 0-5° C. for 1 hour and then at room temperature for 1.5 hours. Cool the mixture to 10° C. and then add saturated aqueous ammonium chloride. Stir the mixture 15 minutes and separate the layers. Extract the aqueous layer with ethyl acetate (400 mL), dry the combined organic layers over sodium sulfate, and concentrate under reduced pressure. Purify the residue by silica gel chromatography, eluting with 1-10% acetonitrile in dichloromethane containing 0.5% triethylamine to provide a 50% yield of the title compound as a white solid. MS(ES+): m/z=488.1 (M+H)+

Workup

  1. stirringStir the resulting slurry at 0-5° C. for 1 hour
  2. waitat room temperature for 1.5 hours
  3. temperatureCool the mixture to 10° C.
  4. stirringStir the mixture 15 minutes
  5. customseparate the layers
  6. extractionExtract the aqueous layer with ethyl acetate (400 mL)
  7. dry with materialdry the combined organic layers over sodium sulfate
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue by silica gel chromatography
  10. washeluting with 1-10% acetonitrile in dichloromethane containing 0.5% triethylamine

Sources & evidence

ORD record
ord-cd79d4e638694177a12ea9cf827d3c69
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

Loading…