Sodium hydride → 1,1-Dimethylethyl N-[[4-fluoro-5-(2-fluoro-3-pyridinyl)-1-[(6-fluoro-2-pyridinyl)sulfonyl]-1H-pyrrol-3-yl]methyl]-N-methylcarbamate

HRID 1426777Notes

Reaction equation

HRID 1426777 reaction equation
[F:1][C:2]1[C:7]([C:8]2[NH:12][CH:11]=[C:10]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]=2[F:23])=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].C1OCCOCCOCCOCCOC1.[F:41][C:42]1[N:47]=[C:46]([S:48](Cl)(=[O:50])=[O:49])[CH:45]=[CH:44][CH:43]=1>O1CCCC1.O>[F:23][C:9]1[C:10]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[CH:11][N:12]([S:48]([C:46]2[CH:45]=[CH:44][CH:43]=[C:42]([F:41])[N:47]=2)(=[O:50])=[O:49])[C:8]=1[C:7]1[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 157295366-Fluoropyridine-2-sulfonyl chlorideHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 673967071,1-Dimethylethyl N-[[4-fluoro-5-(2-fluoro-3-pyridinyl)-1-[(6-fluoro-2-pyridinyl)sulfonyl]-1H-pyrrol-3-yl]methyl]-N-methylcarbamateYield 32.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 2-(benzylthio)-6-fluoropyridine (310 mg) in acetic acid (3 mL) and water (1.5 mL) was added N-chlorosuccinimide (776 mg), and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated under reduced pressure, toluene was added to the residue, the mixture was filtrated, and the filtrate was concentrated under reduced pressure to give crude 6-fluoropyridine-2-sulfonyl chloride (240 mg). To a solution of tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (102 mg) in tetrahydrofuran (3 mL) was added sodium hydride (60% in oil, 37 mg) at 0° C., and the mixture was stirred at the same temperature for 15 min. 15-Crown-5 (0.19 mL), then a solution of crude 6-fluoropyridine-2-sulfonyl chloride (240 mg) in tetrahydrofuran (2 mL) were added at the same temperature, and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=2:1) to give the title compound as a brown oil (yield 49 mg, 7% from 2-(benzylthio)-6-fluoropyridine).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=2:1)

Sources & evidence

ORD record
ord-38902eb12a394229a978bd5d8c88f802
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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