Sodium hydride → HCID 67397648, compound

HRID 1426696Notes

Reaction equation

HRID 1426696 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[CH2:13][N:14]([CH2:16][C:17]1[C:21]([F:22])=[C:20]([C:23]2[C:24]([F:29])=[N:25][CH:26]=[CH:27][CH:28]=2)[NH:19][CH:18]=1)[CH3:15].C1OCCOCCOCCOCCOC1.[N:45]1[CH:50]=[CH:49][CH:48]=[C:47]([S:51](Cl)(=[O:53])=[O:52])[CH:46]=1>O1CCCC1>[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[CH2:13][N:14]([CH2:16][C:17]1[C:21]([F:22])=[C:20]([C:23]2[C:24]([F:29])=[N:25][CH:26]=[CH:27][CH:28]=2)[N:19]([S:51]([C:47]2[CH:46]=[N:45][CH:50]=[CH:49][CH:48]=2)(=[O:53])=[O:52])[CH:18]=1)[CH3:15]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 3164136Pyridine-3-sulfonyl chlorideHCID 67396635HCID 67396635, compound

Product 1

HCID 67397648HCID 67397648, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 1.57 g) in tetrahydrofuran (100 mL) was added dropwise a solution of 1-(2,4-dimethoxyphenyl)-N-{[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}-N-methylmethanamine (9.8 g) in tetrahydrofuran (30 mL) under ice-cooling. The reaction mixture was stirred at the same temperature for 10 min, and 15-crown-5 (8.66 g) was added dropwise. After further stirring for 10 min, pyridine-3-sulfonyl chloride (6.98 g) was added dropwise. After stirring for 15 min at the same temperature, ice water was added and the reaction mixture was extracted with ethyl acetate. The aqueous layer was weakly basified with saturated aqueous sodium hydrogen carbonate solution (100 mL), and extracted again with ethyl acetate. The combined extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=6:1→3:1), and washed with diisopropyl ether to give the title compound as colorless crystals (yield 9.25 g, 69%).

Workup

  1. temperaturecooling
  2. stirringAfter further stirring for 10 min
  3. additionwas added
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. extractionextracted again with ethyl acetate
  6. extractionThe combined extract
  7. washwas washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=6:1→3:1)
  11. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-3769e0d4e9c9469b845a0ab05d0ab192
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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