Potassium Hydroxide → 2-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

HRID 595647Notes

Reaction equation

[Cl:1][C:2]1[N: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][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][CH:13]=[C:14]([F:17])[C:15]=4[CH:16]=[C:8]3[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-(6-chloro-3-vinylpyridin-2-yl)-4-fluoro-1H-indole (1.0 g, 3.7 mmol), DMSO (2.5 mL), TBAC (0.3 mL, 50% aq. solution) and KOH (10 mL, 60% a.q. solution) was stirred under N2 at 100° C. for 4 h. After cooled to RT and extracted with CH2Cl2, the organic layer was washed with water, brine, dried over Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography (PE:EA=100:1˜10:1) to give the product of 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (0.5 g, yield: 50%). And 150 mg of un-reacted 2-(6-chloro-3-vinylpyridin-2-yl)-4-fluoro-1H-indole was recycled during the column purification. 1H-NMR (CDCl3, 400 MHz) δ 7.50 (d, J=7.8 Hz, 1H), 7.38 (s, 1H), 7.22˜7.04 (m, 3H), 6.86˜6.71 (m, 1H), 4.27 (t, J=6.8 Hz, 2H), 3.22 (t, J=6.8 Hz, 2H). MS (M+H)+: 273.

Workup

temperatureAfter cooled to RT
extractionextracted with CH2Cl2
washthe organic layer was washed with water, brine
dry with materialdried over Na2SO4
concentrationconcentrated on a rotary evaporator
customThe residue was purified by column chromatography (PE:EA=100:1˜10:1)

Sources & evidence

ORD record: ord-b4c3460de1e44166b48e4871adc74038
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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