Water → 6-Bromo-2-(4-methanesulfonyl-benzyl)-7-methyl-8-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one

HRID 1497767Notes

Reaction equation

HRID 1497767 reaction equation
[Br:1][C:2]1[C:3]([CH3:22])=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[C:5]2[N:6]([C:8](=[O:11])[NH:9][N:10]=2)[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:29][S:30]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=1)(=[O:32])=[O:31].O>CN(C=O)C>[Br:1][C:2]1[C:3]([CH3:22])=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[CH:13]=2)[C:5]2[N:6]([C:8](=[O:11])[N:9]([CH2:37][C:36]3[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:40][CH:39]=3)[N:10]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonate2×HCID 27335814-(Methylsulfonyl)benzyl Bromide2×HCID 867081016-Bromo-7-methyl-8-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one

Product 1

HCID 867081026-Bromo-2-(4-methanesulfonyl-benzyl)-7-methyl-8-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-oneYield 61.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-7-methyl-8-(3-trifluoromethyl-phenyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one (Int. 15, 55 mg, 0.148 mmol) in DMF (3 mL) was added cesium carbonate (58 mg, 0.177 mmol) followed by 4-(methylsulfonyl)benzyl bromide (40 mg, 0.163 mmol) and the mixture was stirred at RT for 20 hrs. Further amounts of cesium carbonate (25 mg) and 4-(methylsulfonyl)benzyl bromide (20 mg) were added and stirring was continued for 2 hrs. Water was added and the mixture was extracted with EtOAc (2×25 mL). The combined organic extracts were washed with brine then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by flash chromatography, eluting with a gradient of 0-100% EtOAc in cyclohexane to give the title compound as a yellow solid (49 mg).

Workup

  1. stirringstirring
  2. waitwas continued for 2 hrs
  3. extractionthe mixture was extracted with EtOAc (2×25 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialthen dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resultant residue was purified by flash chromatography
  9. washeluting with a gradient of 0-100% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-ac09267342804ac6994b94ebc79103f0
Source dataset
uspto-grants-2015_12
Patent number
US09199984B2

Reaction notes

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