2-Thiophenecarboxaldehyde → 1-Isopropylsulfonyl-2-amino-6-(2-(thien-2-yl)-5-(phenyl)-imidazol-4-yl)-benzimidazole methanesulfonate

HRID 2252063Notes

Reaction equation

HRID 2252063 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[O:7].[CH:8]([S:11]([N:14]1[C:18]2[CH:19]=[C:20]([C:23](=O)[CH:24](O[Si](C(C)(C)C)(C)C)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH2:40])(=[O:13])=[O:12])([CH3:10])[CH3:9].C([O-])(=O)C.[NH4+:45].[Cl-].[NH4+:47].[OH-].[NH4+]>C(O)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CO.C(OCC)(=O)C>[CH3:8][S:11]([OH:13])(=[O:7])=[O:12].[CH:8]([S:11]([N:14]1[C:18]2[CH:19]=[C:20]([C:23]3[N:45]=[C:6]([C:2]4[S:1][CH:5]=[CH:4][CH:3]=4)[NH:47][C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH2:40])(=[O:13])=[O:12])([CH3:10])[CH3:9]

Participants

10

Reactant 5

HCID 73642-ThiophenecarboxaldehydeHCID 14923Ammonium Hydroxide2×HCID 25517Ammonium ChlorideHCID 517165Ammonium AcetateHCID 11340754HCID 11340754, compound

Product 1

HCID 179817351-Isopropylsulfonyl-2-amino-6-(2-(thien-2-yl)-5-(phenyl)-imidazol-4-yl)-benzimidazole methanesulfonateYield 40%

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
97.5 °C

Procedure

Add thiophene-2-carboxaldehyde (3.16 mL, 33.8 mmol) to a stirring mixture of 1-isopropylsulfonyl-2-amino-6-(α-((tert-butyldimethylsilyl)oxy)-α-(phenyl)acetyl)-benzimidazole (15.0 g, 30.8 mmol), copper(II) acetate (11.2 g, 61.5 mmol), and ammonium acetate (23.7 g, 308 mmol) in acetic acid (300 mL). Heat the mixture at 95-100° C. and stir vigorously for 2 hours. Cool the mixture to 15° C., pour into a mixture of 750 mL saturated aqueous ammonium chloride and 250 mL concentrated ammonium hydroxide. Adjust the mixture to pH 10 with ammonium hydroxide precooled to 5° C. and then add 4 L 4:1 ethyl acetate:methanol. Separate the layers and wash the organic layer with saturated aqueous ammonium chloride (500 mL), dry over magnesium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography eluting with dichloromethane containing from 15-50% acetonitrile and 0.5% triethylamine. Suspend the recovered material in ethanol (75 mL), warm to 55-60° C. for 30 minutes, cool to −10° C. for 30 minutes, filter, wash sequentially with cold ethanol followed by diethyl ether. Dry under reduced pressure to provide the title compound in 40% yield as a dark yellow powder. MS(ES+): m/z=464.1 (M+H)+

Workup

  1. temperatureCool the mixture to 15° C.
  2. customprecooled to 5° C.
  3. customSeparate the layers
  4. washwash the organic layer with saturated aqueous ammonium chloride (500 mL)
  5. dry with materialdry over magnesium sulfate
  6. concentrationconcentrate under reduced pressure
  7. washeluting with dichloromethane containing from 15-50% acetonitrile and 0.5% triethylamine
  8. temperaturewarm to 55-60° C. for 30 minutes
  9. temperaturecool to −10° C. for 30 minutes
  10. filtrationfilter
  11. washwash sequentially with cold ethanol
  12. customDry under reduced pressure

Sources & evidence

ORD record
ord-3583828766e1418fbdb49f24ee9c01b6
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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