Sodium hydride → 1-(((5S,7S)-3-((5-ethoxypyrazin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Participants

Reaction Steps

To a solution of 1-{[(5S,7S)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile (150 mg, 0.462 mmol) in N,N-Dimethylformamide (DMF) (2 mL) was added 60% sodium hydride in mineral oil (24.04 mg, 0.601 mmol) and stirred for 30 minutes. To the mixture was added 2-(bromomethyl)-5-ethoxypyrazine (120 mg, 0.555 mmol) and stirred overnight. The reaction was diluted with saturated NH4Cl and extracted with ethyl acetate (3×). The combined organic extracts were washed with saturated NaCl (2×), dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel ISCO chromatography (40 g silica gel, 40 mL/min, 0-10% MeOH/CH2Cl2 over 25 min) to afford 1-(((5S,7S)-3-((5-ethoxypyrazin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (125 mg, 56%). 1H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.35 (d, J=0.75 Hz, 1H), 8.21 (d, J=1.25 Hz, 1H), 8.13 (d, J=1.51 Hz, 1H), 7.83 (d, J=8.28 Hz, 1H), 7.59 (dd, J=8.28, 1.51 Hz, 1H), 4.31-4.41 (m, 4H), 4.12 (s, 2H), 3.21 (dd, J=23.09, 9.03 Hz, 2H), 1.81 (d, J=13.30 Hz, 1H), 1.49-1.74 (m, 4H), 1.22-1.46 (m, 6H), 1.02 (s, 3H). MS (m/z) 461.2 (M+H+).

Provenance & Evidence