Ethyl Acetate → 5-({3-fluoro-2-(2-fluoropyridin-3-yl)-4-[(methylamino)methyl]-1H-pyrrol-1-yl}sulfonyl)-2-furonitrile fumarate

HRID 1426823Notes

Reaction equation

HRID 1426823 reaction equation
[C:1]([C:3]1[O:7][C:6]([S:8]([N:11]2[C:15]([C:16]3[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=3)=[C:14]([F:23])[C:13]([CH2:24][N:25](C)[C:26](=O)OC(C)(C)C)=[CH:12]2)(=[O:10])=[O:9])=[CH:5][CH:4]=1)#[N:2].[C:34]([O:37]CC)(=[O:36])[CH3:35].Cl.[C:41]([O:44]CC)(=[O:43])[CH3:42]>CC(O)C>[C:41]([OH:44])(=[O:43])/[CH:42]=[CH:35]/[C:34]([OH:37])=[O:36].[F:23][C:14]1[C:13]([CH2:24][NH:25][CH3:26])=[CH:12][N:11]([S:8]([C:6]2[O:7][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)(=[O:10])=[O:9])[C:15]=1[C:16]1[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 67397187tert-butyl {[1-[(5-cyano-2-furyl)sulfonyl]-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 673969115-({3-fluoro-2-(2-fluoropyridin-3-yl)-4-[(methylamino)methyl]-1H-pyrrol-1-yl}sulfonyl)-2-furonitrile fumarateYield 23%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of tert-butyl {[1-[(5-cyano-2-furyl)sulfonyl]-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate (253 mg) in ethyl acetate (2 mL) and 2-propanol (1 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (3 mL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. A solution of the residue in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (27.6 mg) in ethanol (2 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound as a white solid (yield 59.3 mg, 23%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with saturated aqueous sodium hydrogen carbonate solution
  3. extractionextracted with ethyl acetate
  4. extractionThe separated aqueous layer was extracted again with ethyl acetate
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionA solution of the residue in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (27.6 mg) in ethanol (2 mL)
  9. concentrationthe mixture was concentrated under reduced pressure
  10. customThe residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-5392986d0f824e97adccac3d6efbf89c
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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