Sodium hydride → 2-(1-{[2-(Trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)pyrazine

HRID 68365Notes

Reaction equation

[N:1]1[C:2]([C:6]2[CH:11]=[N:10][CH:9]=[CH:8][N:7]=2)=[N:3][CH2:4][CH:5]=1.[H-].[Na+].Cl[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20]>CN(C=O)C>[CH3:20][Si:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][O:16][CH2:15][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:11]=[N:10][CH:9]=[CH:8][N:7]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of 2-(4H-imidazol-2-yl)pyrazine (0.75 g, 5.1 mmol) in DMF (7 mL) was added sodium hydride (60% dispersion in oil, 0.42 g, 10.3 mmol) and the reaction stirred at 40° C. for 2 hours. [2-(chloromethoxy)ethyl](trimethyl)silane (1.71 g, 10.3 mmol) was added and the reaction was stirred at 40° C. for a further 3 hours The reaction mixture was partitioned between EtOAc and water and the layers separated. The aqueous layers was extracted with EtOAc (×2) and the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 20-60% EtOAc in hexane) to give the title compound (0.88 g, yellow oil). 1H NMR (400 MHz, CDCl3) δ ppm: 9.47 (d, J=1.0 Hz, 1 H), 8.36-8.59 (m, 2 H), 7.26-7.28 (m, 1 H), 7.24 (d, J=1.3 Hz, 1 H), 5.96-6.00 (m, 2 H), 3.53-3.61 (m, 2 H), 0.86-0.94 (m, 2 H), −0.10-−0.05 (m, 9 H).

Workup

stirringthe reaction was stirred at 40° C. for a further 3 hours The reaction mixture
customwas partitioned between EtOAc and water
customthe layers separated
extractionThe aqueous layers was extracted with EtOAc (×2)
dry with materialthe combined organic layers were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified

Sources & evidence

ORD record: ord-58ea1cfeccb441f19315ef2c43c4c5cb
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822455B2

Reaction notes

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