Acetic Acid → 5-Chloro-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol

HRID 1262432Notes

Reaction equation

HRID 1262432 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[N:5]2[C:10]=1[CH:9]=[N:8][C:7](SC)=[N:6]2.C(O)(=[O:23])C.OO.[OH-].[Na+]>CO.O.O.[O-][W]([O-])(=O)=O.[Na+].[Na+].O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[N:5]2[C:10]=1[CH:9]=[N:8][C:7]([OH:23])=[N:6]2

Participants

9

Reactant 4

HCID 176Acetic Acid2×HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 667114975-Chloro-7-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 1784885945-Chloro-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-olYield 30.1%

Reagents, catalysts & solvents 4

HCID 150191Sodium Tungstate DihydrateCatalystHCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

5-Chloro-7-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (114 mg, 0.372 mmol) was dissolved in Methanol (12.0 mL): Tetrahydrofuran (8.0 mL), Acetic acid (0.200 mL, 3.52 mmol) was added followed by Sodium Tungstate Dihydrate (7.0 mg, 0.021 mmol) and 50% Hydrogen Peroxide (0.100 mL, 1.76 mmol) and the mixture was heated at 60-80° C. overnight in a vial. LCMS shows conversion to a mixture of sulfoxide and sulfone. The mixture was cooled, added portionwise to stirring water (60 mL) and let stand. The solids were collected, washing with water. The crude 5-Chloro-2-methanesulfonyl-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazine was suspended in 1,4-Dioxane (3.00 mL): 5.0 M of Sodium hydroxide in Water (0.50 mL, 2.5 mmol) and heated at 60° C. for 2 h, then cooled and treated with Acetic acid (0.200 mL, 3.52 mmol) and water (1 mL). The solids were let stand 1 h, then collected. Product was also in the aq. layer, which was extr. with DCM (3×20 mL), comb. with the solids and conc. in vacuo onto 3 g silica gel. Purification (ISCO, 0-80% EtOAc:Hex) afforded 5-Chloro-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (31 mg; Yield=30%) as yellow solids.

Workup

  1. temperatureThe mixture was cooled
  2. additionadded portionwise
  3. customThe solids were collected
  4. washwashing with water
  5. temperaturecooled
  6. customcollected
  7. customPurification (ISCO, 0-80% EtOAc:Hex)

Sources & evidence

ORD record
ord-64d8cb9f976f4d82bd4788baa97e853d
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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