Sodium hydride → HCID 178419418, compound

HRID 1693716Notes

Reaction equation

[Br:1][C:2]1[C:3](Cl)=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:17][CH2:18][OH:19])=[CH:9][N:8](COCC[Si](C)(C)C)[C:5]2=[N:6][CH:7]=1.[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[NH:8][CH:9]=[C:10]3[C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH2:12][CH2:17][C:18]=4[O:19][C:3]=1[C:4]=23

Participants

Conditions

Temperature: 80 °C

Procedure

2-{2-[5-Bromo-4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-phenyl}-ethanol was dissolved in DMF (20 mL) and sodium hydride (100 mg) was added until the gas evolution stops. The mixture was stirred at 80° C. for 12 h. The reaction was quenched with saturated ammonium chloride solution (5 mL) and concentrated. The solid was suspended in water (20 mL) and was applied to a Varian chemelut cartridge and eluted with ethyl acetate. The crude product was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes followed by mass triggered reverse phase HPLC to afford 5-Bromo-7,8-dihydro-2H-6-oxa-2,3-diaza-benzocycloocta[cd]indene (28.6 mg, 0.09 mmol, 23% yield). 1H NMR (500 MHz, MeCN-d3) δ 12.18 (s, 1H), 8.33 (s, 1H), 7.62 (d, J=2.5 Hz, 1H), 7.47 (m, 1H), 7.38 (m, 1H), 7.29 (m, 2H), 4.30 (t, J=6 Hz, 2H), 2.91 (t, J=6 Hz, 2H). MS: m/z 315.0/317.0 (M+H+) and 5-Bromo-2-(2-trimethylsilanyl-ethoxymethyl)-7,8-dihydro-2H-6-oxa-2,3-diaza-benzocycloocta[cd] indene (45 mg, 0.01 mmol, 26% yield).

Workup

customThe reaction was quenched with saturated ammonium chloride solution (5 mL)
concentrationconcentrated
washeluted with ethyl acetate
customThe crude product was purified by flash silica gel chromatography

Sources & evidence

ORD record: ord-2832925043084b7caa122396170c0e63
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158647B2

Reaction notes

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