Cesium carbonate → 2-Bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine

HRID 595682Notes

Reaction equation

HRID 595682 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[C:17]([F:20])[CH:16]=[CH:15][CH:14]=3)[C:5]([CH2:8][CH2:9]Cl)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[CH2:8][CH2:9][N:12]3[C:13]4[CH:14]=[CH:15][CH:16]=[C:17]([F:20])[C:18]=4[CH:19]=[C:11]3[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 903335962-(5-bromo-2-(2-chloroethyl)pyridin-3-yl)-4-fluoro-1H-indole

Product 1

HCID 903336942-Bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridineYield 83.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(5-bromo-2-(2-chloroethyl)pyridin-3-yl)-4-fluoro-1H-indole (800 mg, 2.26 mmol) and cesium carbonate (1.47 g, 4.52 mmol) in 25 mL of DMF was heated at 80° C. for 1 hour. The mixture was concentrated in vacuo to remove DMF, and then the residue was suspended in water and EA. After extraction with EA, the combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford crude 2-bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine (600 mg, yield: 83.6%) which was used directly in the next step without further purification. 1H-NMR (CDCl3, 400 MHz) δ 8.48 (s, 1H), 8.11 (s, 1H), 7.11˜7.17 (m, 2H), 6.97 (s, 1H), 6.78˜6.82 (m, 1H), 4.34˜4.37 (m, 2H), 3.34˜3.37 (m, 2H). MS (M+H)+: 317/319.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto remove DMF
  3. extractionAfter extraction with EA
  4. washthe combined organic phase was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3d2b79bd6ad245169c2c0f4f0c61ba95
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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