Sodium hydride → 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

HRID 886621Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][N:8]([CH2:21][O:20][CH2:19][CH2:18][Si:15]([CH3:17])([CH3:16])[CH3:14])[C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: -40 °C

Procedure

To a 500 ml 3-neck flask, 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (32 g, 99.1 mmol) and DMF (300 ml) were added. The solution was cooled to −40° C. under nitrogen and sodium hydride (2.8 g, 118.9 mmol) was added in 2 batches. The mixture was stirred at −40° C. for 1 hour. Then SEM-Cl (21 ml, 118.9 mmol) in DMF (50 ml) was added drop wise and the resulting mixture was allowed to stir at −40° C. for another 2 hours. The reaction was quenched with saturated NH4Cl (40 ml) and worked up with ethyl acetate, brine, dried with Na2SO4, concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (32.8 g, 73% yield). NMR (500 MHz, DMSO-d6) δ 0.06 (s, 9H), 0.91 (m, 2H), 3.62 (m, 2H), 5.70 (s, 2H), 8.04 (m, 1H), 8.11 (s, 1H), 8.51 (m, 1H). MS: m/z 455.9 (M+H+).

Workup

stirringto stir at −40° C. for another 2 hours
customThe reaction was quenched with saturated NH4Cl (40 ml)
dry with materialdried with Na2SO4
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-55b7cca2520c4bb9a4a579a42307c864
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242280B2

Reaction notes

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