Dimethyl Sulfoxide → HCID 69221745, compound

HRID 2055135Notes

Reaction equation

HRID 2055135 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[N:11]1([C:20]([CH3:24])([CH3:23])[CH2:21]O)[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[N:13]=[CH:12]1.C(N(CC)CC)C.[H-].[Na+].C(OP([CH2:42][C:43]([O:45][CH3:46])=[O:44])(OCC)=O)C>ClCCl.C1COCC1.O>[CH3:46][O:45][C:43](=[O:44])[CH:42]=[CH:21][C:20]([N:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[N:13]=[CH:12]1)([CH3:24])[CH3:23]

Participants

10

Reactant 6

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 66113Methyl diethylphosphonoacetateHCID 11513907HCID 11513907, compound

Product 1

HCID 69221745HCID 69221745, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. cooled stirred solution of oxalyl chloride (1 eq) in dichloromethane was added dimethyl sulfoxide (2 eq). After an additional 5 minutes, 2-imidazo[4,5-b]pyridin-1-yl-2-methyl-propan-1-ol (1 eq) dissolved in dichloromethane was added to the cooled solution via cannula. The resulting heterogeneous mixture was stirred at −78° C. for 30 minutes, and triethylamine (5 eq) was added to produce a thick white slurry. After stirring at −78° C. for 15 minutes, the mixture was allowed to warm slowly to 0° C., diluted with dichloromethane, washed with NaCl (sat.), dried over sodium sulfate, filtered, and concentrated. Following this, to a solution of sodium hydride (1 eq) in THF was added methyl diethylphosphonoacetate (1 eq) at 0° C. The mixture was stirred at room temperature for 30 minutes and a solution of the latter concentrated residue dissolved in THF was added dropwise to the mixture. The solution was stirred for 1 hour at the same temperature and then poured into H2O, followed by an extraction with ethyl acetate. The organic layer was washed with NaCl (sat.), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography using a solvent gradient of 97% DCM, 3% MeOH, and 0.1% TEA to yield 4-imidazo[4,5-b]pyridin-1-yl-4-methyl-pent-2-enoic acid methyl ester (93%). MH+(246)

Workup

  1. additionwas added to the cooled solution via cannula
  2. customto produce a thick white slurry
  3. stirringAfter stirring at −78° C. for 15 minutes
  4. temperatureto warm slowly to 0° C.
  5. washwashed with NaCl (sat.)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. stirringThe mixture was stirred at room temperature for 30 minutes
  10. additionwas added dropwise to the mixture
  11. stirringThe solution was stirred for 1 hour at the same temperature
  12. extractionfollowed by an extraction with ethyl acetate
  13. washThe organic layer was washed with NaCl (sat.)
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-c4c0266843fb48d3a8c9ab2d0a29af82
Source dataset
uspto-grants-2008_02
Patent number
US07332476B2

Reaction notes

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