Water → 7-(2-Methoxy-phenyl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine

HRID 1261880Notes

Reaction equation

HRID 1261880 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1.Br[C:27]1[N:35]2[C:30]([CH:31]=[N:32][C:33]([S:36][CH3:37])=[N:34]2)=[CH:29][CH:28]=1.[CH3:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1B(O)O.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:27]1[N:35]2[C:30]([CH:31]=[N:32][C:33]([S:36][CH3:37])=[N:34]2)=[CH:29][CH:28]=1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 27339582-Methoxyphenylboronic acidHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 667115487-(2-Methoxy-phenyl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazineYield 78%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

7-(2-Methoxy-phenyl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]: Into a 200 mL round bottom flask, Palladium Acetate (0.20 g, 0.00088 mol) and Triphenylphosphine (0.65 g, 0.0025 mol) were added. The mixture was purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (66.8 mL, 0.856 mol) was added and stirred for 10 minutes at room temperature. 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (2.150 g, 0.008807 mol), 2-methoxybenzeneboronic acid (2.68 g, 0.0176 mol), N,N-Dimethylformamide (130 mL, 1.7 mol), and 1.50 M of Sodium carbonate in Water (52.8 mL, 0.0793 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 desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 3% methanol). The collected fractions afforded 7-(2-Methoxy-phenyl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine as a yellow solid (1.85 g, 78%). NMR 1H (DSMO-d6)-8.89 (s, 1H), 7.81 (dd, 1H, JJ=2.74, 6.01 Hz), 7.42 (td, 1H, JJ=1.68, 6.92 Hz), 7.07-7.25 (m, 4H), 3.81 (s, 3H), 2.43 (s, 3H)

Workup

  1. customThe mixture was purged under an atmosphere of Nitrogen for 10 minutes
  2. temperatureThe reaction was heated at 90° C. for 3 hours
  3. customThe reaction was partitioned with water and EtOAc
  4. customThe organic was separated
  5. washwashed with Brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationThe solid was filtered
  8. washwashed with EtOAc
  9. customThe solvent was removed under vacuum
  10. customThe desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 3% methanol)

Sources & evidence

ORD record
ord-ea77a903580c4082b95eedf4102cf1fd
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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