Dimethyl Sulfoxide → 2-Chloro-11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridine

HRID 595675Notes

Reaction equation

HRID 595675 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([CH:18]=[CH2:19])=[CH:4][N:3]=1.CS(C)=O.[OH-].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:18][CH2:19][N:9]3[C:10]4[CH:11]=[CH:12][CH:13]=[C:14]([F:17])[C:15]=4[CH:16]=[C:8]3[C:6]=2[CH:7]=1

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 14797Potassium HydroxideHCID 903335672-(2-chloro-5-vinylpyridin-4-yl)-4-fluoro-1H-indole

Product 1

HCID 903334612-Chloro-11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridineYield 22.4%

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(2-chloro-5-vinylpyridin-4-yl)-4-fluoro-1H-indole (50 mg, 0.18 mmol), Bu4NCl (0.07 mL of 50% a.q. solution), DMSO (0.25 mL) and KOH (0.6 mL of 60% a.q. solution) was stirred at 100° C. for 3 hours. Then the mixture was diluted with H2O, extracted with EtOAc, then the combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product. It was purified by column (PE:EA=3:1) to obtain the product of 2-chloro-11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridine (11 mg, yield: 20%). 1H-NMR (CDCl3, 400 MHz) δ 8.30 (s, 1H), 7.62 (s, 1H), 7.18˜7.21 (m, 2H), 7.12 (s, 1H), 6.81 (t, J=8.4 Hz, 1H), 4.29 (t, J=6.0 Hz, 2H), 3.20 (t, J=6.0 Hz, 2H). MS (M+H)+: 273/275.

Workup

  1. extractionextracted with EtOAc
  2. washthe combined organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customIt was purified by column (PE:EA=3:1)

Sources & evidence

ORD record
ord-5469b66f999143ca927cc92efe775ebd
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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