Triethylamine → HCID 25002633, compound

HRID 1426788Notes

Reaction equation

HRID 1426788 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:32]=[N:33][CH:34]=[CH:35][CH:36]=2)(=[O:30])=[O:29])[CH:16]=1)C.C(Cl)(=O)OC(Cl)C.C(N(CC)CC)C>O1CCCC1>[F:20][C:19]1[C:15]([CH2:14][NH:12][CH3:11])=[CH:16][N:17]([S:28]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=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

5

Reactant 3

HCID 8471TriethylamineHCID 5213051-Chloroethyl chloroformateHCID 67397648HCID 67397648, compound

Product 1

HCID 25002633HCID 25002633, compoundYield 77.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-(2,4-dimethoxyphenyl)-N-{[4-fluoro-5-(2-fluoropyridin-3-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}-N-methylmethanamine (5.68 g) in tetrahydrofuran (25 mL) was added a solution of 1-chloroethyl chlorocarbonate (1.58 g) in tetrahydrofuran (5 mL) at 0° C., and the mixture was stirred for 15 min. Triethylamine (4.63 mL) was added and the obtained mixture was stirred at 65° C. for 16 hr. The obtained solid was filtrated and the filtrate was concentrated under reduced pressure. Water 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. Ethanol (25 mL) was added to the residue, and the mixture was refluxed for 1.5 hr, and concentrated under reduced pressure. Ethyl acetate was added to the residue, and the precipitated solid was filtrated. To the obtained solid were successively added ethyl acetate, 1 mol/L aqueous sodium hydroxide solution and saturated aqueous sodium hydrogen carbonate solution, and the mixture was stirred at room temperature for 10 min. The organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=1:1→1:4) to give the title compound as a colorless oil (yield 3.10 g, 77%).

Workup

  1. stirringthe obtained mixture was stirred at 65° C. for 16 hr
  2. filtrationThe obtained solid was filtrated
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionWater was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. additionEthanol (25 mL) was added to the residue
  10. temperaturethe mixture was refluxed for 1.5 hr
  11. concentrationconcentrated under reduced pressure
  12. additionEthyl acetate was added to the residue
  13. filtrationthe precipitated solid was filtrated
  14. stirringthe mixture was stirred at room temperature for 10 min
  15. customThe organic layer was separated
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=1:1→1:4)

Sources & evidence

ORD record
ord-7ea8be1c8b5344468ad237595cdd6cb9
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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