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Hydrogen chloride-ethyl acetate → 1-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine

HRID 869766
Notes
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Reaction equation

HRID 869766 reaction equation
[F:1][C:2]1[C:3]([CH2:24][N:25](C)[C:26](=O)OC(C)(C)C)=[CH:4][N:5]([S:14]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][C:22]=2[CH3:23])(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1.C(OCC)(=O)C.Cl>C(OCC)(=O)C.CC(O)C>[F:1][C:2]1[C:3]([CH2:24][NH:25][CH3:26])=[CH:4][N:5]([S:14]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][C:22]=2[CH3:23])(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 67176706tert-Butyl ({4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}methyl)methylcarbamate

Product 1

HCID 671775211-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamineYield 97%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent
HCID 8857
Ethyl Acetate
Solvent

Procedure

To a solution of tert-butyl ({4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}methyl)methylcarbamate (127 mg) in ethyl acetate (2 mL) and 2-propanol (0.5 mL) was added 4N hydrogen chloride-ethyl acetate solution (2 mL), and the mixture was stirred at room temperature for 2 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 to give 1-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine as a pale-yellow oil (yield 97 mg, 97%). A solution of the obtained 1-{4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (30 mg) in ethanol (2 mL) and concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound as a white solid (yield 103 mg, 81%).

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. washCombined organic layers were washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-277c42b8927a41f19f9685e2e834108c
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08969387B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes