Water → 3-[3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-propionitrile

HRID 1262270Notes

Reaction equation

HRID 1262270 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([S:30][CH3:31])=[N:28]2)=[CH:23][CH:22]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[C:42]([CH2:46][CH2:47][C:48]#[N:49])[CH:43]=[CH:44][CH:45]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[CH3:31][S:30][C:27]1[N:26]=[CH:25][C:24]2=[CH:23][CH:22]=[C:21]([C:40]3[CH:41]=[C:42]([CH2:46][CH2:47][C:48]#[N:49])[CH:43]=[CH:44][CH:45]=3)[N:29]2[N:28]=1

Participants

8

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazineHCID 592765613-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzenepropanenitrile

Product 1

HCID 667119783-[3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-propionitrileYield 74.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

Into a 8-dram vial, Palladium Acetate (0.057 g, 0.26 mmol) and Triphenylphosphine (0.19 g, 0.00072 mol) were added. The mixture was purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (19.4 mL) was added and stirred for 10 minutes at room temperature. 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.623 g, 2.55 mmol), 3-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionitrile (1.31 g, 5.10 mmol), N,N-Dimethylformamide (39 mL), and 1.50 M of Sodium carbonate in Water (15.3 mL, 0.0230 mol) were added. The reaction was heated at 90° C. for 3 hours. The reaction was partitioned with water and EtOAc. The organic was separated, washed with Brine, and dried over magnesium sulfate. The solid was filtered and washed with EtOAc. The solvent was removed under vacuum. The product was isolated via column chromatography with DCM and Methanol as eluant (1 to 8% MeOH). The collected fractions afforded a solid. The solid was triturated with Et2O and filtered to give 3-[3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-propionitrile as a yellow solid (560 mg, 64%).

Workup

  1. customThe mixture was purged under an atmosphere of Nitrogen for 10 minutes
  2. addition1,4-Dioxane (19.4 mL) was added
  3. temperatureThe reaction was heated at 90° C. for 3 hours
  4. customThe reaction was partitioned with water and EtOAc
  5. customThe organic was separated
  6. washwashed with Brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe solid was filtered
  9. washwashed with EtOAc
  10. customThe solvent was removed under vacuum
  11. customThe product was isolated via column chromatography with DCM and Methanol as eluant (1 to 8% MeOH)
  12. customThe collected fractions afforded a solid
  13. customThe solid was triturated with Et2O
  14. filtrationfiltered

Sources & evidence

ORD record
ord-4e3cf30cc665451bbda6c095a529dea2
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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