Triethylamine → N-[7-Methyl-6-propionyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]acetamide

HRID 1497805Notes

Reaction equation

HRID 1497805 reaction equation
Br[C:2]1[C:3]([CH3:25])=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:5]2[N:6]([N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[CH:7]=1.C([O:28][CH:29]=[CH:30][CH3:31])C.C(N(CC)CC)C.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:25][C:3]1[C:2]([C:29](=[O:28])[CH2:30][CH3:31])=[CH:7][N:6]2[N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=[C:5]2[C:4]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 13570Ethyl 1-propenyl etherHCID 80271Tri-o-tolylphosphineHCID 86708104N-[6-Bromo-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-acetamide

Product 1

HCID 86708113N-[7-Methyl-6-propionyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]acetamideYield 11%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-[6-bromo-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-acetamide (Int. 18, 0.5 g, 1.21 mmol) was combined with ethyl-1-propenyl ether (125 mg, 1.45 mmol), triethylamine (202 μL, 1.45 mmol), palladium (II) acetate (3 mg, 0.012 mmol), tri-O-tolylphosphine (15 mg, 0.048 mmol) in DMF (7 mL) was degassed and then heated at 130° C. for 5 hrs. Further amounts of palladium (II) acetate (3 mg) and ethyl-1-propenyl ether (125 mg) were added and heating was continued for 5 days. 1 M HCl (5 mL) was added and the mixture was stirred vigorously for 40 mins. The mixture was partitioned between EtOAc (100 mL) and water (100 mL) and the organic layer was washed with saturated brine, then dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by chromatography, eluting with a gradient of 0-10% MeOH in DCM followed by trituration with DCM and ether. The resultant precipitate was collected by filtration and dried to afford the title compound as a white solid (11%)

Workup

  1. customwas degassed
  2. additionFurther amounts of palladium (II) acetate (3 mg) and ethyl-1-propenyl ether (125 mg) were added
  3. temperatureheating
  4. addition1 M HCl (5 mL) was added
  5. customThe mixture was partitioned between EtOAc (100 mL) and water (100 mL)
  6. washthe organic layer was washed with saturated brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by chromatography
  10. washeluting with a gradient of 0-10% MeOH in DCM
  11. filtrationThe resultant precipitate was collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-e52ac95d9fcd4496801771e070b2d775
Source dataset
uspto-grants-2015_12
Patent number
US09199984B2

Reaction notes

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