2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol

HRID 244391Notes

Reaction equation

HRID 244391 reaction equation
C(=O)=O.CC(C)=O.Br[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[N:13]=[CH:12]2.C([Li])CCC.[F:30][C:31]([F:44])([F:43])[C:32]([C:34]1[C:42]2[C:37](=[N:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1)=[O:33]>C1COCC1.[Cl-].[NH4+]>[F:44][C:31]([F:30])([F:43])[C:32]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[N:13]=[CH:12]2)([C:34]1[C:42]2[C:37](=[N:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1)[OH:33]

Participants

7

Reactant 4

HCID 57078082,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanoneHCID 18522661Acetone cardice2×HCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 178418339Butyllithium

Product 1

HCID 249594552,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanolYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a chilled (−78° C.) (dry ice-acetone) solution of 291 mg (1.0 mmol) of 5-bromo-1-(4-fluorophenyl)-1H-indazole in 5 mL of anhydrous THF was added rapidly 0.4 mL (1.0 mmol) of a 2.5 M solution of n-butyllithium (n-BuLi) in hexanes. Immediately after, a chilled (dry ice-acetone bath) solution of 2,2,2-trifluoro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone (prepared according to the procedure described in J. Org. Chem. 2002, 76, 6226) in 3 mL of THF was added rapidly. The mixture stirred for 1 hour, TLC [ethyl acetate-hexanes (1:1)] indicated a new more polar product than both starting materials. The mixture was diluted with 10 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel using dichloromethane to load the sample and then eluting with ethyl acetate-CH2Cl2 (0-30% gradient). The material from the column was solidified from ether-hexanes (1:1), dried under house vacuum at 90° C. for 3 hours, to afford 91 mg (42%) of the title compound. MS m/z 427.18 (MH+).

Workup

  1. customprepared
  2. extractionextracted with three 10 mL portions of ethyl acetate
  3. washThe combined organic layers were washed with three 10 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was chromatographed on silica gel
  8. washeluting with ethyl acetate-CH2Cl2 (0-30% gradient)
  9. customdried under house vacuum at 90° C. for 3 hours

Sources & evidence

ORD record
ord-ae3b38035f4d4242989bf37837e8c76e
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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