Tetrahydrofuran → N-methyl-1-[1-(5-methyl-3-pyridinesulfonyl)-5-phenyl-1H-pyrrol-3-yl]methanamine Fumarate

HRID 554454Notes

Reaction equation

HRID 554454 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:14][C:13]([CH2:22][N:23](C)[C:24](=O)OC(C)(C)C)=[CH:12]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[CH3:32].NN.[C:35](=[O:38])([O-:37])O.[Na+].[O:40]1[CH2:44][CH2:43][CH2:42]C1>>[C:44]([OH:40])(=[O:9])/[CH:43]=[CH:42]/[C:35]([OH:37])=[O:38].[CH3:24][NH:23][CH2:22][C:13]1[CH:14]=[C:15]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:11]([S:8]([C:5]2[CH:6]=[N:7][CH:2]=[C:3]([CH3:32])[CH:4]=2)(=[O:10])=[O:9])[CH:12]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 9321HydrazineHCID 516892Sodium BicarbonateHCID 86620771tert-butyl{[1-(6-chloro-5-methyl-3-pyridinesulfonyl)-5-phenyl-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 66925269N-methyl-1-[1-(5-methyl-3-pyridinesulfonyl)-5-phenyl-1H-pyrrol-3-yl]methanamine Fumarate

Procedure

To a solution (5 mL) of tert-butyl {[1-(6-chloro-5-methyl-3-pyridinesulfonyl)-5-phenyl-1H-pyrrol-3-yl]methyl}methylcarbamate (237 mg) in tetrahydrofuran was added hydrazine (160 mg) with stirring at room temperature. After stirring at the same temperature for 3 hr, saturated aqueous sodium hydrogencarbonate solution was added 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. The residue was dissolved in tetrahydrofuran (30 mL), manganese dioxide (75% chemically-treated product, 1.0 g) was added, the mixture was stirred at room temperature for 10 min. The reaction product was filtered through celite, and the celite was washed with ethyl acetate. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→1:1) to give N-Boc-compound (129 mg) of the title compound. The obtained N-Boc compound was dissolved in ethanol (2 mL), and a 4 mol/L hydrogen chloride-ethyl acetate solution (1 mL) was added. After stirring at room temperature for 2 hr, the solvent was evaporated under reduced pressure, saturated aqueous sodium hydrogencarbonate solution was added, 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. The residue (93 mg) was dissolved in methanol (3 mL), and fumaric acid (29 mg) was added. The mixture was stood at room temperature for 30 min, and the precipitated crystals were collected by filtration and washed with methanol to give the title compound as a colorless solid (yield 91 mg, 40%).

Workup

  1. stirringAfter stirring at the same temperature for 3 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in tetrahydrofuran (30 mL)
  7. additionmanganese dioxide (75% chemically-treated product, 1.0 g) was added
  8. stirringthe mixture was stirred at room temperature for 10 min
  9. filtrationThe reaction product was filtered through celite
  10. washthe celite was washed with ethyl acetate
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→1:1)

Sources & evidence

ORD record
ord-7ac1da0fb63a43f99e2b5c06206cbd4e
Source dataset
uspto-grants-2011_11
Patent number
US08048909B2

Reaction notes

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