Trifluoroacetic acid → 7-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one

HRID 244455Notes

Reaction equation

HRID 244455 reaction equation
Cl[C:2]1[C:3]2[NH:10][CH:9]=[C:8]([C:11]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[N:21]=[CH:20]4)([OH:16])[C:12]([F:15])([F:14])[F:13])[C:4]=2[N:5]=[CH:6][N:7]=1.FC(F)(F)C(O)=[O:36]>O.O1CCOCC1.C([O-])(O)=O.[Na+]>[F:13][C:12]([F:15])([F:14])[C:11]([C:8]1[C:4]2[N:5]=[CH:6][NH:7][C:2](=[O:36])[C:3]=2[NH:10][CH:9]=1)([C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]1[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=1)[N:21]=[CH:20]2)[OH:16]

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 24958369HCID 24958369, compound

Product 1

HCID 1359078507-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-oneYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol (43 mg, 0.09 mmol) and 1 mL of trifluoroacetic acid in 1 mL of water and 2 mL of dioxane was warmed at 70° C. After 18 hours, the reaction was diluted with saturated NaHCO3 and extracted with EtOAc. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was dissolved in 1 mL of DMF and purified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA). The desired fractions were combined and the CH3CN was removed in vacuo. The aqueous layer was made basic with saturated sodium bicarbonate and extracted with EtOAc. The combined organics were dried, filtered, and concentrated in vacuo to provide 18 mg (44%) of the title compound as a white solid. MS m/z 444.27 (MH+).

Workup

  1. extractionextracted with EtOAc
  2. customThe combined organic layers were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 1 mL of DMF
  6. custompurified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA)
  7. customthe CH3CN was removed in vacuo
  8. extractionextracted with EtOAc
  9. customThe combined organics were dried
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bb1bb965d51f490297b167aff1b7d304
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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