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

HRID 1426821Notes

Reaction equation

HRID 1426821 reaction equation
[F:1][C:2]1[C:3]([CH2:24][N:25]([CH3:33])C(=O)OC(C)(C)C)=[CH:4][N:5]([S:14]([C:17]2[O:18][C:19]([CH2:22][OH:23])=[CH:20][CH:21]=2)(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1.[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].[C:34]([O:23][CH2:22][C:19]1[O:18][C:17]([S:14]([N:5]2[CH:4]=[C:3]([CH2:24][NH:25][CH3:33])[C:2]([F:1])=[C:6]2[C:7]2[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=2)(=[O:16])=[O:15])=[CH:21][CH:20]=1)(=[O:36])[CH3:35]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 67398835tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(hydroxymethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate

Product 1

HCID 69036245[5-({3-fluoro-2-(2-fluoropyridin-3-yl)-4-[(methylamino)methyl]-1H-pyrrol-1-yl}sulfonyl)-2-furyl]methyl acetate fumarate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(hydroxymethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate (223 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 solvent was concentrated under reduced pressure, the residue was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate solution. 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. The residue was purified by basic silica gel column chromatography (eluent:hexane-ethyl acetate=2:3→ethyl acetate) to give the title compound as a free base (basic TLC:Rf=0.22 (hexane:ethyl acetate=1:1)) (yield 42.2 mg). A solution of the obtained free base (42.2 mg) in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (11.5 mg) in ethanol (2 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-ethanol to give the title compound as a white solid (yield 37.4 mg, 23%).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed with saturated aqueous sodium hydrogen carbonate solution
  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. customThe residue was purified by basic silica gel column chromatography (eluent:hexane-ethyl acetate=2:3→ethyl acetate)

Sources & evidence

ORD record
ord-7e7f846a733449ea857d5029016ba4c5
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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