Indole → 1-(2-chloro-5-fluoro-pyrimidin-4-yl)-1H-indole

HRID 1947036Notes

Reaction equation

HRID 1947036 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([F:20])=[CH:15][N:14]=1.O>CN(C=O)C>[Cl:12][C:13]1[N:18]=[C:17]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[C:16]([F:20])=[CH:15][N:14]=1

Participants

6

Reactant 4

HCID 798IndoleHCID 962WaterHCID 24758Sodium hydrideHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 866208441-(2-chloro-5-fluoro-pyrimidin-4-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Indole (1.0 g, 8.54 mmol) was added in portions to a suspension of NaH (0.358 g, 8.96 mmol) in DMF (10 mL) at 0° C. under N2 and stirred for 15 minutes at RT. 2,4-Dichloro-5-fluoro-pyrimidine (1.49 g, 8.96 mmol) was then added in portions and allowed to stir at RT overnight. The reaction mixture was poured into cold water, extracted into DCM, washed in brine, dried with Na2SO4, filtered, and dried in vacuo to obtain an oil. The residue was purified using flash chromatography on a silica column eluting with hexane:EtOAc (1000:25) to (1000:50), to yield 1-(2-chloro-5-fluoro-pyrimidin-4-yl)-1H-indole after drying the collected fraction (0.11 g, 5%).

Workup

  1. stirringto stir at RT overnight
  2. extractionextracted into DCM
  3. washwashed in brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. customdried in vacuo
  7. customto obtain an oil
  8. customThe residue was purified
  9. washeluting with hexane:EtOAc (1000:25) to (1000:50)

Sources & evidence

ORD record
ord-37aac2291ecb4202b6f20a584b925413
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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