Water → HCID 25007649, compound

HRID 1426789Notes

Reaction equation

HRID 1426789 reaction equation
COC1C=C(OC)C=CC=1[CH2:11][N:12]([CH2:14][C:15]1[C:19]([F:20])=[C:18]([C:21]2[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=2)[N:17]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH:16]=1)C.C(Cl)(=O)OC(Cl)C.C(N(CC)CC)C.O>O1CCCC1>[F:20][C:19]1[C:15]([CH2:14][NH:12][CH3:11])=[CH:16][N:17]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[C:18]=1[C:21]1[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 5213051-Chloroethyl chloroformateHCID 67397692HCID 67397692, compound

Product 1

HCID 25007649HCID 25007649, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-(2,4-dimethoxyphenyl)-N-{[4-fluoro-5-(2-fluoropyridin-3-yl)-1-(phenylsulfonyl)-1H-pyrrol-3-yl]methyl}-N-methylmethanamine (2.75 g) in tetrahydrofuran (10 mL) was added a solution of 1-chloroethyl chlorocarbonate (781 mg) in tetrahydrofuran (2 mL) at 0° C., and the mixture was stirred for 15 min. Triethylamine (2.3 mL) was added and the obtained mixture was refluxed for 16 hr. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Ethanol (12 mL) was added to the residue, and the mixture was refluxed for 1.5 hr, and concentrated under reduced pressure. Saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: ethyl acetate:methanol=9:1→1:1) to give the title compound as a yellow solid (yield 1.46 g, 75%).

Workup

  1. temperaturethe obtained mixture was refluxed for 16 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionEthanol (12 mL) was added to the residue
  7. temperaturethe mixture was refluxed for 1.5 hr
  8. concentrationconcentrated under reduced pressure
  9. additionSaturated aqueous sodium hydrogen carbonate solution was added to the residue
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by basic silica gel column chromatography (eluent: ethyl acetate:methanol=9:1→1:1)

Sources & evidence

ORD record
ord-1f0bd8ae1b5a459dab42524561b4bb46
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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