Dimethylformamide → (5-bromo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)(4-chlorophenyl)methanone

HRID 2401982Notes

Reaction equation

HRID 2401982 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:14]=[CH:13][S:12][C:11]=2[C:15]2[N:19]=[CH:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[N:16]=2)=[O:9])=[CH:4][CH:3]=1.CN(C)C=O.[Br:31]N1C(=O)CCC1=O>O.C(=O)(O)[O-].[Na+]>[Br:31][C:13]1[S:12][C:11]([C:15]2[N:19]=[CH:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[N:16]=2)=[C:10]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:9])[CH:14]=1

Participants

6

Reactant 3

HCID 6228Dimethylformamide2×HCID 67184N-bromobutanimide2×HCID 66749278(4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)methanone

Product 1

HCID 66749271(5-bromo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)(4-chlorophenyl)methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of (4-chlorophenyl){2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanone (20.2 g, 54.0 mmol) in N,N-dimethylformamide (350 mL, 4500 mmol) was added dropwise a solution of N-bromosuccinimide (14.42 g, 81.05 mmol) in N,N-dimethylformamide (50 mL, 600 mmol) under argon. The mixture was stirred at rt with care taken to block the reaction from exposure to ambient light. After 3 h reaction, LCMS showed both starting material and product. Additional N-bromosuccinimide (6.732 g, 37.82 mmol) was added and the mixture was stirred at rt again. After stirring overnight, the mixture was diluted with water and sodium bicarbonate solution and then the mixture was extracted with EtOAc. The organic layer was washed with water and brine. The EtOAc layer was dried and evaporated in vacuum to a residue, which was purified by chromatography to afford (5-bromo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)(4-chlorophenyl)methanone as a white solid (18.0, 73.5%). LCMS: (FA) ES+ 451.9, 453.9

Workup

  1. customthe reaction from exposure to ambient light
  2. customAfter 3 h reaction, LCMS
  3. stirringthe mixture was stirred at rt again
  4. stirringAfter stirring overnight
  5. extractionthe mixture was extracted with EtOAc
  6. washThe organic layer was washed with water and brine
  7. dry with materialThe EtOAc layer was dried
  8. customevaporated in vacuum to a residue, which
  9. customwas purified by chromatography

Sources & evidence

ORD record
ord-c44b404fbd014a9799b021fc75b5432e
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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