Sodium Iodide → 5-(Benzoxazol-2-yl)-2-benzylaminomethyl-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74202Notes

Reaction equation

HRID 74202 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:26]=[CH:25][C:13]2[N:14]([CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[C:15]([CH2:17]O)=[N:16][C:12]=2[CH:11]=1.S(Cl)(Cl)=O.[I-].[Na+].[CH2:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>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:26]=[CH:25][C:13]2[N:14]([CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[C:15]([CH2:17][NH:40][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[N:16][C:12]=2[CH:11]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 7504BenzylamineHCID 24386Thionyl ChlorideHCID 674979855-(Benzoxazol-2-yl)-2-hydroxymethyl-1-(tetrahydropyran-4-yl)benzimidazole

Product 1

HCID 498214585-(Benzoxazol-2-yl)-2-benzylaminomethyl-1-(tetrahydropyran-4-yl)benzimidazoleYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 5-(benzoxazol-2-yl)-2-hydroxymethyl-1-(tetrahydropyran-4-yl)benzimidazole (see Working Example 13-2) (168 mg, 0.481 mmol) was added thionyl chloride (1.5 mL), and this was heated to reflux with stirring for 2 hours. After the reaction was complete, this was cooled to room temperature and concentrated. The crystals obtained were suspended in tetrahydrofuran, and to this was added sodium iodide (108 mg, 0.722 mmol) and benzylamine (258 mg, 2.41 mmol), and this was heated to reflux with stirring for 1.5 hours. After the reaction was complete, this was cooled to room temperature, water was added, and this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated to give an residue that was purified by silica gel column chromatography to yield the title compound (182 mg, 86% yield) as a colorless amorphous mass.

Workup

  1. temperaturethis was heated
  2. temperatureto reflux
  3. concentrationconcentrated
  4. customThe crystals obtained
  5. temperaturethis was heated
  6. temperatureto reflux
  7. stirringwith stirring for 1.5 hours
  8. temperaturethis was cooled to room temperature
  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 an residue that
  15. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fbf1b2fbbeb04907aa5c9739d1ef654f
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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