Methanesulfonic Acid → 5-(Benzoxazol-2-yl)-2-(2-(methylthio)ethyl)-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74314Notes

Reaction equation

HRID 74314 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[CH:12][C:13]([NH:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[C:14]([CH:16]=1)[NH2:15].[CH3:24][S:25][CH2:26][CH2:27][C:28](Cl)=O.C(N(CC)CC)C.CS(O)(=O)=O.[OH-].[Na+]>O1CCCC1.O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[CH:12][C:13]2[N:17]([CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:28]([CH2:27][CH2:26][S:25][CH3:24])=[N:15][C:14]=2[CH:16]=1

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 129214403-(Methylthio)propionyl ChlorideHCID 674988065-(Benzoxazol-2-yl)-2-(tetrahydropyran-4-yl)aminoaniline

Product 1

HCID 674985555-(Benzoxazol-2-yl)-2-(2-(methylthio)ethyl)-1-(tetrahydropyran-4-yl)benzimidazoleYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(benzoxazol-2-yl)-2-(tetrahydropyran-4-yl)aminoaniline (see Working Example 20-2) (200 mg, 0.646 mmol) in tetrahydrofuran (5 mL) was added 3-(methylthio)propionyl chloride (98.5 mg, 0.711 mmol) and triethylamine (131 mg, 1.29 mmol), and this was stirred at room temperature for 7 hours. After the reaction was complete, water was added and this was extracted with ethyl acetate. After the organic layer obtained was dried over anhydrous sodium sulfate, it was filtered and concentrated. To a solution of the residue obtained in dioxane (5 mL) was added methanesulfonic acid (0.5 mL), and this was heated to reflux for 3 hours. After the reaction was complete, 1M aqueous sodium hydroxide solution was added, and this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated to give crude crystals that were purified by silica gel column chromatography to yield the title compound (170 mg, 67% yield) as colorless crystals.

Workup

  1. extractionthis was extracted with ethyl acetate
  2. customAfter the organic layer obtained
  3. dry with materialwas dried over anhydrous sodium sulfate, it
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customTo a solution of the residue obtained in dioxane (5 mL)
  7. temperaturethis was heated
  8. temperatureto reflux for 3 hours
  9. extractionthis was extracted with ethyl acetate
  10. customThe organic layer obtained
  11. dry with materialwas dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give crude crystals that
  15. customwere purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e991e3b3e90c4f65bb2af5baec9b596d
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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