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

HRID 74233

Reaction equation

HRID 74233 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.S(Cl)(Cl)=O.[NH2:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=1O.C(N(CC)CC)C.CS(O)(=O)=O.C(=O)([O-])O.[Na+]>O.O1CCCC1>[N+:32]([C:30]1[CH:29]=[CH:28][C:27]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:25][C:26]=2[CH:31]=1)([O-:34])=[O:33]

Participants

9

Reactant 6

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 36133892-Amino-4-NitrophenolHCID 674984452-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt

Product 1

HCID 674990855-(5-Nitrobenzoxazol-2-yl)-2-methyl-1-(tetrahydropyran-4-yl)benzimidazoleYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) (264 mg, 0.888 mmol) was added thionyl chloride (2 mL), and this was stirred at reflux for 3 hours. After the reaction was complete, concentration at reduced pressure gave a residue that was added to 2-amino-4-nitrophenol (137 mg, 0.888 mmol), triethylamine (449 mg, 4.44 mmol) and tetrahydrofuran (10 mL), and this was stirred at room temperature for 14 hours. After the reaction was complete, this was concentrated, and to a dioxane (5 mL) solution of the residue obtained was added methanesulfonic acid (140 mg, 1.46 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 (66 mg, 20% yield) as white crystals.

Workup

  1. temperatureat reflux for 3 hours
  2. concentrationconcentration at reduced pressure
  3. customgave a residue that
  4. stirringthis was stirred at room temperature for 14 hours
  5. concentrationthis was concentrated
  6. customto a dioxane (5 mL) solution of the residue 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-abb474d254884240bd109191583b4145
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Linked notes

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