Potassium Hydroxide → 2-Chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

HRID 595659Notes

Reaction equation

HRID 595659 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([F:17])=[CH:12][CH:11]=3)[C:5]([CH:18]=[CH2:19])=[CH:4][CH:3]=1.[OH-].[K+]>CCCC[N+](CCCC)(CCCC)CCCC.[Cl-].CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:18][CH2:19][N:9]3[C:10]4[CH:11]=[CH:12][C:13]([F:17])=[CH:14][C:15]=4[CH:16]=[C:8]3[C:6]=2[N:7]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 903339502-(6-chloro-3-vinylpyridin-2-yl)-5-fluoro-1H-indole

Product 1

HCID 903334282-Chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridineYield 50.9%

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(6-chloro-3-vinylpyridin-2-yl)-5-fluoro-1H-indole (100 mg, 0.36 mmol), DMSO (0.5 mL), TBAC (0.1 mL of 50% a.q. solution) and KOH (1.0 mL of 60% a.q. solution) was stirred under N2 at 100° C. for 4 h. After cooled and extracted with EtOAc, the organic layer was washed with water, brine, dried over Na2SO4, and concentrated. The residue was purified by prep-TLC (PE:EA=10:1) to give the product of 2-chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, yield: 50.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.51 (d, J=8.0 Hz, 1H), 7.25˜7.38 (m, 3H), 7.15 (d, J=8.0 Hz, 1H), 6.98˜7.04 (m, 1H), 4.26 (d, J=6.4 Hz, 2H), 3.22 (d, J=6.4 Hz, 2H). MS (M+H)+: 273/275.

Workup

  1. temperatureAfter cooled
  2. extractionextracted with EtOAc
  3. washthe organic layer was washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by prep-TLC (PE:EA=10:1)

Sources & evidence

ORD record
ord-e11f2d32e876405abfbec2a0288975c8
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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