Trifluoroacetic acid → 5-Allyl-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 244451Notes

Reaction equation

HRID 244451 reaction equation
[CH2:1]([N:4]1[C:12]2[C:11](Cl)=[N:10][CH:9]=[N:8][C:7]=2[C:6]([C:14]([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:24]=[CH:23]3)([OH:19])[C:15]([F:18])([F:17])[F:16])=[CH:5]1)[CH:2]=[CH2:3].FC(F)(F)C(O)=[O:39].C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[CH2:1]([N:4]1[C:12]2[C:11](=[O:39])[NH:10][CH:9]=[N:8][C:7]=2[C:6]([C:14]([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:24]=[CH:23]3)([OH:19])[C:15]([F:18])([F:17])[F:16])=[CH:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 594371991-(5-Allyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

Product 1

HCID 1359078495-Allyl-7-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-oneYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(5-allyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol (250 mg, 0.5 mmol) in 3 mL of dioxane was added 2 mL of water followed by 2 mL of trifluoroacetic acid. The mixture was warmed at 80° C. for 1.5 hours, cooled to room temperature and made basic with saturated sodium bicarbonate, diluted with water, and extracted with EtOAc. The combined organic layers were dried, filtered, and evaporated. The residue was purified by flash chromatography eluting with MeOH—CH2Cl2 (0-2% gradient) to provide 129 mg (53%) of the title compound as a white solid. MS m/z 484.33 (MH+).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash chromatography
  7. washeluting with MeOH—CH2Cl2 (0-2% gradient)

Sources & evidence

ORD record
ord-17d2f8e383514052bceda7f8b43bede0
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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