Methanesulfonic Acid → 5-(5-Methoxybenzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74238Notes

Reaction equation

HRID 74238 reaction equation
Cl.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:6]2[CH:14]=[CH:15][C:16]([C:18]([OH:20])=O)=[CH:17][C:5]=2[N:4]=1.N[C:22]1[C:27]([O:28][CH3:29])=[CH:26][CH:25]=[CH:24][C:23]=1O.CC[N:33]=C=NCCCN(C)C.CS(O)(=O)=O.C(=O)([O-])O.[Na+]>O.CN(C=O)C>[CH3:29][O:28][C:27]1[CH:26]=[CH:25][C:24]2[O:20][C:18]([C:16]3[CH:15]=[CH:14][C:6]4[N:7]([CH:8]5[CH2:9][CH2:10][O:11][CH2:12][CH2:13]5)[C:3]([CH3:2])=[N:4][C:5]=4[CH:17]=3)=[N:33][C:23]=2[CH:22]=1

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516892Sodium BicarbonateHCID 214926222-Amino-3-methoxyphenolHCID 674984452-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt

Product 1

HCID 674981705-(5-Methoxybenzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazoleYield 3.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) ((250 mg, 0.842 mmol), 2-amino-3-methoxyphenol (139 mg, 0.842 mmol), DMF (5 mL), and WSC (178 mg, 0.926 mmol) were stirred for 22 hours. Water was added and this was extracted with chloroform. After the organic layer obtained was dried over anhydrous sodium sulfate, it was filtered and concentrated. To a dioxane (5 mL) solution of the solid obtained was added methanesulfonic acid (283 mg, 2.95 mmol), and this was heated to reflux for 18 hours. After the reaction solution was cooled, water and saturated aqueous sodium hydrogen carbonate solution were added, and this was extracted with chloroform. After the organic layer obtained was dried over anhydrous sodium sulfate, it was filtered and concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (10 mg, 3.3% yield) as brown crystals.

Workup

  1. extractionthis was extracted with chloroform
  2. customAfter the organic layer obtained
  3. dry with materialwas dried over anhydrous sodium sulfate, it
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customTo a dioxane (5 mL) solution of the solid obtained
  7. temperaturethis was heated
  8. temperatureto reflux for 18 hours
  9. temperatureAfter the reaction solution was cooled
  10. extractionthis was extracted with chloroform
  11. customAfter the organic layer obtained
  12. dry with materialwas dried over anhydrous sodium sulfate, it
  13. filtrationwas filtered
  14. concentrationconcentrated
  15. customThe residue obtained
  16. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-988f7cb6f5f746099d1c8f63c4fb5d31
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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