Methanesulfonyl chloride → HCID 86619141, compound

HRID 2238659Notes

Reaction equation

HRID 2238659 reaction equation
[F:1][CH:2]([F:31])[C:3]1[C:4]2[N:5]([C:9]([C:12]3[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]([NH:20][CH:21]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29]O)[CH:24]=4)[CH3:22])[N:13]=3)=[CH:10][N:11]=2)[CH:6]=[CH:7][CH:8]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.C(=O)([O-])O.[Na+].[N-:51]=[N+:52]=[N-:53].[Na+]>C(Cl)(Cl)Cl.CN(C)C=O>[N:51]([CH2:29][C:25]1[CH:24]=[C:23]([CH:21]([NH:20][C:14]2[N:13]=[C:12]([C:9]3[N:5]4[CH:6]=[CH:7][CH:8]=[C:3]([CH:2]([F:31])[F:1])[C:4]4=[N:11][CH:10]=3)[C:17]([C:18]#[N:19])=[CH:16][N:15]=2)[CH3:22])[CH:28]=[CH:27][CH:26]=1)=[N+:52]=[N-:53]

Participants

8

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 81531DiisopropylethylamineHCID 516892Sodium Bicarbonate2×HCID 68687123HCID 68687123, compound

Product 1

HCID 86619141HCID 86619141, compoundYield 65.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

125 mg of the 4-[8-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]-2-({1-[3-(hydroxymethyl)phenyl]ethyl]amino]pyrimidin-5-carbonitrile [101-1] and 259 μL of N,N-diisopropylethylamine were dissolved in 3 mL of chloroform, then 69 μL of methanesulfonyl chloride was added under an ice-cold condition, and stirred at the same temperature for 30 minutes. Thereto, a saturated aqueous solution of sodium hydrogen carbonate was added, and extracted with chloroform. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The insolubles were filtered and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was dissolved in 3 mL of N,N-dimethylformamide. Thereto, 97 mg of sodium azide was added, and stirred at 80° C. for 1 hour. The reaction solution was cooled back to room temperature, then a saturated aqueous solution of sodium hydrogen carbonate was added, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The insolubles were filtered and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was purified by preparative thin-layer chromatography, and 87 mg of 2-({1-[3-(azidomethyl)phenyl)ethyl}amino)-4-[8-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-5-carbonitrile [102-1] was obtained as a light brown oily product.

Workup

  1. extractionextracted with chloroform
  2. washThe obtained organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insolubles were filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customto obtain a residue
  7. stirringstirred at 80° C. for 1 hour
  8. extractionextracted with ethyl acetate
  9. washThe obtained organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationThe insolubles were filtered
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customto obtain a residue
  14. customThe residue was purified by preparative thin-layer chromatography

Sources & evidence

ORD record
ord-840f1c2b1bfe46e19628f3293b490ee2
Source dataset
uspto-grants-2010_05
Patent number
US07718801B2

Reaction notes

Loading…