Cesium carbonate → N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

HRID 578864Notes

Reaction equation

HRID 578864 reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:25])[C:5]([C:8]2([CH2:11][NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH:26]1([B-](F)(F)F)[CH2:28][CH2:27]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.O>[Cl:25][C:4]1[C:5]([C:8]2([CH2:11][NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])[CH2:10][CH2:9]2)=[N:6][CH:7]=[C:2]([CH:26]2[CH2:28][CH2:27]2)[CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 89544470N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

Product 1

HCID 71558842N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamideYield 44.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

150 mg of N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide (step 4), 61 mg potassium cyclopropyltrifluoroborate and 340 mg cesium carbonate were dissolved in 3 ml of a mixture of toluene and water (3:1) in a microwave vial. The reaction mixture was degassed with argon for 1 min and 14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added. The vial was sealed and the reaction mixture was then stirred at 100° C. in a microwave reactor for 30 min, then at 130° C. for 30 min. Then the mixture was cooled to ambient temperature, water was added and the reaction mixture was extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. Crude material was obtained as a brown sticky solid, which was purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent. Thus, 61 mg of N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide was obtained as a pale yellow sticky solid. 1H-NMR (CDCl3): 8.19 ppm (d, 1H), 7.65 ppm (d, 1H), 7.52 ppm (m, 2H), 7.40 ppm (d, 1H), 7.30 ppm (d, 1H), 6.20 ppm (s, 1H, broad), 3.68 ppm (d, 2H), 1.85 ppm (m, 1H), 1.05 ppm (m, 5H), 0.88 ppm (m, 1H), 0.70 ppm (m, 2H).

Workup

  1. customThe reaction mixture was degassed with argon for 1 min
  2. addition14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added
  3. customThe vial was sealed
  4. waitat 130° C. for 30 min
  5. temperatureThen the mixture was cooled to ambient temperature
  6. additionwater was added
  7. extractionthe reaction mixture was extracted with dichloromethane
  8. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customCrude material was obtained as a brown sticky solid, which
  12. customwas purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent

Sources & evidence

ORD record
ord-12db9d251a2d4220b14781ab6ed69bc5
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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