Borane;tetrahydrofuran → 3-[4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]propan-1-ol

HRID 1398901Notes

Reaction equation

HRID 1398901 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([N:11]([C:19]3[CH:20]=[N:21][C:22]([N:26]([CH3:28])[CH3:27])=[CH:23][C:24]=3[CH3:25])C(=O)OC(C)(C)C)[N:7]([CH2:29][CH:30]=C)[C:6]=2[C:5]([CH:32]([CH2:35][CH3:36])[CH2:33][CH3:34])=[CH:4][CH:3]=1.B.[O:38]1CCC[CH2:39]1.O.O.O.O.B(O[O-])([O-])[O-].[Na+].[Na+].[Na+]>O1CCCC1.O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:19]3[CH:20]=[N:21][C:22]([N:26]([CH3:28])[CH3:27])=[CH:23][C:24]=3[CH3:25])[N:7]([CH2:29][CH2:30][CH2:39][OH:38])[C:6]=2[C:5]([CH:32]([CH2:35][CH3:36])[CH2:33][CH3:34])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 2723981Borane;tetrahydrofuranHCID 18380057Sodium peroxyborate tetrahydrateHCID 86632906tert-Butyl [4-chloro-7-(1-ethylpropyl)-1-prop-2-en-1-yl-1H-benzimidazol-2-yl][6-(dimethylamino)-4-methylpyridin-3-yl]carbamate

Product 1

HCID 687713093-[4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]propan-1-olYield 29.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl [4-chloro-7-(1-ethylpropyl)-1-prop-2-en-1-yl-1H-benzimidazol-2-yl][6-(dimethylamino)-4-methylpyridin-3-yl]carbamate (450 mg, 0.88 mmol) in tetrahydrofuran (8.8 mL) was added borane-tetrahydrofuran complex (1.18 M in tetrahydrofuran, 7.46 mL, 8.8 mmol) at room temperature. After stirring for 2 hr, the mixture was poured into a suspension of sodium peroxyborate tetrahydrate (2.03 g, 13.2 mmol) in water (10 mL). The mixture was stirred for 14 hr at room temperature. The mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in methanol (5 mL) followed by addition of 6 N hydrochloric acid (5 mL). After stirring for 14 hr at room temperature, aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture to give the title compound (110 mg, 0.26 mmol, 29%) as a colorless solid.

Workup

  1. stirringThe mixture was stirred for 14 hr at room temperature
  2. extractionThe mixture was extracted with ethyl acetate
  3. washOrganic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in methanol (5 mL)
  7. additionfollowed by addition of 6 N hydrochloric acid (5 mL)
  8. stirringAfter stirring for 14 hr at room temperature
  9. additionaqueous sodium bicarbonate was added
  10. extractionthe mixture was extracted with ethyl acetate
  11. washOrganic layer was washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-ec539100ce0c45f69f865aa3cd7d8937
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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