Water → N-{2-[2-Methylsulfanyl-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-methanesulfonamide

HRID 1262334Notes

Reaction equation

HRID 1262334 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)=[C:23]([O:32][CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:22]=1.CC1(C)C(C)(C)OB([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[NH:55][S:56]([CH3:59])(=[O:58])=[O:57])O1.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][S:30][C:27]1[N:26]=[CH:25][C:24]2=[C:23]([O:32][CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:22]=[C:21]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=3[NH:55][S:56]([CH3:59])(=[O:58])=[O:57])[N:29]2[N:28]=1

Participants

8

Reactant 6

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 43565252-(Methanesulfonylamino)phenylboronic acid pinacol esterHCID 667122877-Bromo-2-methylsulfanyl-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 66712259N-{2-[2-Methylsulfanyl-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-methanesulfonamideYield 78%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Into a 30 mL vial, Palladium Acetate (0.043 g, 0.19 mmol) and Triphenylphosphine (0.14 g, 0.54 mmol) were added. The mixture was purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (14.6 mL) was added and stirred for 10 minutes at room temperature. 7-Bromo-2-methylsulfanyl-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazine (0.750 g, 1.92 mmol), N-[2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-methanesulfonamide (1.14 g, 3.84 mmol), N,N-Dimethylformamide (29 mL, 380 mmol), and 1.50 M of Sodium carbonate in Water (11.5 mL, 17.3 mmol) 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 (0 to 5% MeOH). The collected fractions afforded a solid. The solid was triturated with Et2O and filtered to give N-{2-[2-Methylsulfanyl-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-methanesulfonamide as a yellow solid (0.72 g, 78%).

Workup

  1. customThe mixture was purged under an atmosphere of Nitrogen for 10 minutes
  2. addition1,4-Dioxane (14.6 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 (0 to 5% MeOH)
  12. customThe collected fractions afforded a solid
  13. customThe solid was triturated with Et2O
  14. filtrationfiltered

Sources & evidence

ORD record
ord-640ff7fae49d4e9e9822ba060e935c65
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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