Sodium hydride → HCID 24960918, compound

HRID 244410Notes

Reaction equation

HRID 244410 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)=[O:4].[H-].[Na+].[Li]CCCC.Br[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[N:28]=[CH:27]2.[Na]>C1COCC1.[Cl-].[NH4+]>[F:15][C:2]([F:1])([F:14])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)([C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[N:28]=[CH:27]2)[OH:4]

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 5891263-(Trifluoroacetyl)indole2×HCID 5360545SodiumHCID 594373015-bromo-1-pyridin-3-yl-1H-indazole2×HCID 178418339Butyllithium

Product 1

HCID 24960918HCID 24960918, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a chilled (−78° C.) solution of 241 mg (1.13 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of anhydrous THF was added 45 mg (1.13 mmol) of 60% NaH in mineral oil. In another flask, 452 μL (1.13 mmol) of n-BuLi was then added to a chilled (−78° C.) solution of 310 mg (1.13 mmol) of 5-bromo-1-pyridin-3-yl-1H-indazole in 10 mL of THF. After 1 minute, the sodium salt of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone was added to the indazole anion via a cannula. After 1 hour, the mixture was diluted with 25 mL of saturated aqueous ammonium chloride and extracted with three 15 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. The crude material was purified using Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 45 mg (10%) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol as a colorless solid.

Workup

  1. waitAfter 1 hour
  2. extractionextracted with three 15 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
  7. customThe crude material was purified

Sources & evidence

ORD record
ord-7f538a75a9ff43918653838bac8f8242
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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