Fumaric Acid → 1-{4-Fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine fumarate

HRID 869761Notes

Reaction equation

HRID 869761 reaction equation
[F:1][C:2]1[C:3]([CH2:24][NH:25][CH3:26])=[CH:4][N:5]([S:14]([C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=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:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31]>C(OCC)(=O)C.C(O)C>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[F:1][C:2]1[C:3]([CH2:24][NH:25][CH3:26])=[CH:4][N:5]([S:14]([C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 2

HCID 444972Fumaric AcidHCID 670842571-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine

Product 1

HCID 671777241-{4-Fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine fumarateYield 88%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl ({4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}methyl)methylcarbamate (107 mg) in ethyl acetate (2 mL) and 2-propanol (1 mL) were 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. Combined organic layers were 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=4:1→1:1) to give 1-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine as a pale-yellow oil (yield 45 mg, 54%). A solution of the obtained 1-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(3-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (14 mg) in ethanol (2 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-ethanol to give the title compound as a white solid (yield 51 mg, 88%).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was recrystallized from ethyl acetate-ethanol

Sources & evidence

ORD record
ord-4071b38c9ebd4ed5a62402a725859d7e
Source dataset
uspto-grants-2015_03
Patent number
US08969387B2

Reaction notes

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