Triethylamine → N-(4-(3-((t-butyl(dimethyl)silyl)oxy)pyrrolidin-2-yl)-3-fluorophenyl)pyridine-2-carboxamide

HRID 13385Notes

Reaction equation

HRID 13385 reaction equation
C([N:3](CC)CC)C.CS(Cl)(=O)=O.[Si:13]([O:20][CH:21]([CH2:40][CH2:41]O)[CH:22]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[O:32])=[CH:26][C:25]=1[F:39])O)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.O>[Si:13]([O:20][CH:21]1[CH2:40][CH2:41][NH:3][CH:22]1[C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[O:32])=[CH:26][C:25]=1[F:39])([C:16]([CH3:18])([CH3:19])[CH3:17])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67483222N-(4-(2-((t-butyl(dimethyl)silyl)oxy)-1,4-dihydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide

Product 1

HCID 67483054N-(4-(3-((t-butyl(dimethyl)silyl)oxy)pyrrolidin-2-yl)-3-fluorophenyl)pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

155 mg of triethylamine and 130 mg of methanesulfonyl chloride were added in order to a chloroform (8 ml) solution of 165 mg of N-(4-(2-((t-butyl(dimethyl)silyl)oxy)-1,4-dihydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide, with cooling with ice, and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 25 mg of sodium azide was added to a dimethylformamide (5 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 50 mg of sodium borohydride and 5 mg of copper sulfate pentahydrate were added in order to a methanol (10 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. 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 the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=50/1) to obtain the entitled compound as a colorless oily substance.

Workup

  1. temperaturewith cooling with ice
  2. customthe reaction liquid
  3. customThe reaction liquid
  4. washwashed with aqueous saturated sodium bicarbonate
  5. dry with materialdried with anhydrous sodium sulfate
  6. customThe solvent was evaporated away under reduced pressure, and 25 mg of sodium azide
  7. additionwas added to a dimethylformamide (5 ml) solution of the resulting residue
  8. customthe reaction liquid
  9. stirringwas stirred at 40° C. for 2 hours
  10. customThe reaction liquid
  11. temperaturewas cooled
  12. extractionextracted with ethyl acetate
  13. dry with materialdried with anhydrous sodium sulfate
  14. customThe solvent was evaporated away under reduced pressure, and 50 mg of sodium borohydride and 5 mg of copper sulfate pentahydrate
  15. additionwere added in order to a methanol (10 ml) solution of the resulting residue
  16. customthe reaction liquid
  17. stirringwas stirred at 40° C. for 2 hours
  18. customThe reaction liquid
  19. temperaturewas cooled
  20. extractionextracted with chloroform
  21. dry with materialdried with anhydrous sodium sulfate
  22. customThe solvent was evaporated away under reduced pressure
  23. customthe resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=50/1)
  24. customto obtain the entitled compound as a colorless oily substance

Sources & evidence

ORD record
ord-9aec69f43fb24331bd1e3296f64869ba
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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