Potassium Carbonate → HCID 57785964, compound

HRID 1628630Notes

Reaction equation

HRID 1628630 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:16]([CH2:17][CH2:18][CH2:19][C:20](OCC)=O)[C:15]2[C:25]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:26][CH:27]=[CH:28][C:14]=2[N:13]=1.[BH4-].[Li+].CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.N1C=CC=CC=1.O.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[N:11]1[C:12]2=[N:13][C:14]3[CH:28]=[CH:27][CH:26]=[C:25]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])[C:15]=3[N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 4148881Lithium borohydrideHCID 68763470Ethyl 4-[2-[(2,4-dimethoxyphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Product 1

HCID 57785964HCID 57785964, compoundYield 29.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 4-[2-[(2,4-dimethoxyphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 56; 569.3 mg, 1.26 mmol) in tetrahydrofuran (5.0 mL) was added lithium borohydride (82.0 mg, 3.77 mmol) at 0° C. The reaction mixture was stirred at 60° C. for 1.5 hr. After cooling, the reaction mixture was quenched with water at 0° C. and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting crude butanol (MS Calcd.: 411; Found: 412 (M+H)) was subjected for the next step without further purification. To a solution of the crude material in pyridine (1.0 mL) was added methanesulfonyl chloride (490 μL, 6.28 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hr. The reaction mixture was quenched with aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude mesylate was subjected for the next step without further purification. To the crude material (MS Calcd.: 489; Found: 490 (M+H)) in NAN-dimethylformamide (1.0 mL) was added potassium carbonate (346.9 mg, 2.51 mmol). The reaction mixture was stirred at 60° C. for 19 hr. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-40% ethyl acetate/n-hexane gradient mixture. The resulting solid was washed with n-hexane to give the title compound as a colorless powder (144.5 mg, 0.367 mmol, 29%).

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was quenched with water at 0° C.
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude butanol (MS Calcd.: 411; Found: 412 (M+H)) was subjected for the next step without further purification
  9. stirringThe reaction mixture was stirred at room temperature for 2 hr
  10. customThe reaction mixture was quenched with aqueous sodium hydrogen carbonate
  11. extractionextracted with ethyl acetate (×3)
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe crude mesylate was subjected for the next step without further purification
  17. stirringThe reaction mixture was stirred at 60° C. for 19 hr
  18. temperatureAfter cooling
  19. extractionextracted with ethyl acetate (×3)
  20. washThe combined organic layer was washed with water (×2) and brine
  21. dry with materialdried over anhydrous magnesium sulfate
  22. filtrationfiltered
  23. concentrationconcentrated in vacuo
  24. customThe residue was purified by silica gel column chromatography
  25. washeluting with a 10-40% ethyl acetate/n-hexane gradient mixture
  26. washThe resulting solid was washed with n-hexane

Sources & evidence

ORD record
ord-b781eb4d1542439586a7290b2352f8f4
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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