4-(5-Tributylstannanyl-pyrazol-1-yl)-benzonitrile → 4-(5-{2-Ethoxy-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-imidazol-4-yl}-1H-pyrazol-1-yl)benzonitrile

HRID 1480020Notes

Reaction equation

HRID 1480020 reaction equation
Br[C:2]1[N:3]=[C:4]([O:18][CH2:19][CH3:20])[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6]=1[CH3:7].C([Sn](CCCC)(CCCC)[C:26]1[N:30]([C:31]2[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=2)[N:29]=[CH:28][CH:27]=1)CCC>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH2:19]([O:18][C:4]1[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6]([CH3:7])=[C:2]([C:26]2[N:30]([C:31]3[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=3)[N:29]=[CH:28][CH:27]=2)[N:3]=1)[CH3:20]

Participants

5

Reactant 2

HCID 867080884-(5-Tributylstannanyl-pyrazol-1-yl)-benzonitrileHCID 1213937334-Bromo-2-ethoxy-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-imidazole

Product 1

HCID 1213937624-(5-{2-Ethoxy-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-imidazol-4-yl}-1H-pyrazol-1-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
94 °C

Procedure

A solution of 4-bromo-2-ethoxy-5-methyl-1-[3-(trifluoromethyl)phenyl]-1H-imidazole (3.14 g, 9 mmol) and 4-(5-tributylstannyl-pyrazol-1-yl)-benzonitrile (see WO2014009425A1, which is incorporated herein by reference in its entierty) (6.19 g, 13.5 mmol) in 1,4-dioxane (45 mL) was degassed by bubbling argon through the solution for 5 minutes. Tetrakis(triphenylphosphine)palladium(O) (0.52 g, 0.45 mmol) was added and after a further period of degassing the mixture was heated at 94° C. under an argon atmosphere during 17 h. The mixture was cooled to RT and filtered through a 50 g flash SCX 2 cartridge. The cartridge was eluted with DCM, 10% methanol in DCM then a 1:1 mixture of 2M ammonia in methanol and DCM. Concentration of the appropriate fractions in vacuo afforded the crude product. This was triturated with cyclohexane and dried in vacuo to afford the title compound (3.01 g).

Workup

  1. customwas degassed
  2. customby bubbling argon through the solution for 5 minutes
  3. customof degassing the mixture
  4. temperatureThe mixture was cooled to RT
  5. filtrationfiltered through a 50 g flash SCX 2 cartridge
  6. washThe cartridge was eluted with DCM, 10% methanol in DCM
  7. additiona 1:1 mixture of 2M ammonia in methanol and DCM
  8. customConcentration of the appropriate fractions in vacuo afforded the crude product
  9. customThis was triturated with cyclohexane
  10. customdried in vacuo

Sources & evidence

ORD record
ord-0661de226b674bac8cb0b0f585f27035
Source dataset
uspto-grants-2016_08
Patent number
US09409870B2

Reaction notes

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