Triethylamine → HCID 23145215, compound

HRID 13397Notes

Reaction equation

HRID 13397 reaction equation
[CH2:1]([N:3](CC)CC)[CH3:2].CS(Cl)(=O)=O.[Si](O[CH2:21][CH2:22][CH:23]([F:42])[CH:24]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)=[O:34])=[CH:28][C:27]=1[F:41])O)(C(C)(C)C)(C)C.C(=O)(O)[O-:44].[Na+]>O.C(Cl)(Cl)Cl>[C:1]([N:3]1[CH2:21][CH2:22][CH:23]([F:42])[CH:24]1[C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)=[O:34])=[CH:28][C:27]=1[F:41])(=[O:44])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium Bicarbonate3×HCID 67482904HCID 67482904, compound

Product 1

HCID 23145215HCID 23145215, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added to a chloroform (5 ml) solution of 100 mg of N-(4-(4-((t-butyl(dimethyl)silyl)oxy)-2-fluoro-1-hydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 22 mg of sodium azide was added to a dimethylformamide (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled, water was added to it, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution) was added to a tetrahydrofuran (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 1 hour. Water was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride were added in order to a chloroform (5 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride were added in order to a methanol (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 1 hour. The reaction liquid was cooled, aqueous saturated sodium bicarbonate was added to it, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine were added in order to a chloroform (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (chloroform/methanol=30/1) to obtain a diastereomer A and a diastereomer B of the entitled compound each as a colorless oily substance.

Workup

  1. customthe reaction liquid
  2. extractionextracted with chloroform
  3. dry with materialdried with anhydrous sodium sulfate
  4. customThe solvent was evaporated away under reduced pressure, and 22 mg of sodium azide
  5. additionwas added to a dimethylformamide (4 ml) solution of the resulting residue
  6. customthe reaction liquid
  7. stirringwas stirred at 40° C. for 2 hours
  8. customThe reaction liquid
  9. temperaturewas cooled
  10. extractionextracted with ethyl acetate
  11. dry with materialdried with anhydrous sodium sulfate
  12. customThe solvent was evaporated away under reduced pressure, and 0.3 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution)
  13. additionwas added to a tetrahydrofuran (4 ml) solution of the resulting residue
  14. customthe reaction liquid
  15. stirringwas stirred at room temperature for 1 hour
  16. extractionextracted with ethyl acetate
  17. dry with materialdried with anhydrous sodium sulfate
  18. customThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine and 39 mg of methanesulfonyl chloride
  19. additionwere added in order to a chloroform (5 ml) solution of the resulting residue
  20. customthe reaction liquid
  21. stirringwas stirred at room temperature for 30 minutes
  22. extractionextracted with ethyl acetate
  23. dry with materialdried with anhydrous sodium sulfate
  24. customThe solvent was evaporated away under reduced pressure, and 10 mg of copper sulfate pentahydrate and 50 mg of sodium borohydride
  25. additionwere added in order to a methanol (4 ml) solution of the resulting residue
  26. customthe reaction liquid
  27. stirringwas stirred at 40° C. for 1 hour
  28. customThe reaction liquid
  29. temperaturewas cooled
  30. extractionextracted with chloroform
  31. dry with materialdried with anhydrous sodium sulfate
  32. customThe solvent was evaporated away under reduced pressure, and 46 mg of triethylamine, 35 mg of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine
  33. additionwere added in order to a chloroform (4 ml) solution of the resulting residue
  34. customthe reaction liquid
  35. stirringwas stirred at room temperature for 30 minutes
  36. customThe solvent was evaporated away under reduced pressure
  37. customthe resulting residue was purified
  38. customthrough partitioning thin-layer chromatography (chloroform/methanol=30/1)
  39. customto obtain a diastereomer A

Sources & evidence

ORD record
ord-22095590eb304554950ce209df473f47
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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