N-methyl-2-pyrrolidone → 1-(((5S,7S)-3-(6-methoxypyridin-3-yl)-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 4 mL vial was added NMP (1997 μL), tert-butyl (6-methoxypyridin-3-yl)carbamate (448 mg, 1.997 mmol) and potassium tert-butoxide (213 mg, 1.898 mmol) at RT. After stirring for ˜1 min at RT, 1-{[(3S,5S)-5-methyl-1-oxaspiro[2.5]oct-5-yl]methyl}-1H-benzimidazole-6-carbonitrile (281 mg, 0.999 mmol) was added. The solution was then heated to 55° C. and stirred for 17 h. The resulting solution was cooled to RT, diluted with 2 mL of MeCN, then purified on HPLC: 20-60% MeCN/Water over 14 min, Sunfire C-18 column, 0.1% TFA. Fractions containing product were added to a separatory funnel, diluted with DCM and saturated NaHCO3. DCM layer was separated, passed over a phase separator and concentrated to give 1-(((5S,7S)-3-(6-methoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (145 mg, 34% yield). 1H NMR (400 MHz, CDCl3) δ 8.08 (dd, J=4, 12 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J=4 Hz, 1H), 7.76 (s, 1H), 7.58 (dd, J=4 Hz, 1H), 6.80 (d, J=12 Hz, 1H), 4.02 (s, 2H), 3.94 (s, 3H), 3.66 (q, J=8 Hz, 2H), 2.14-2.18 (m, 1H), 1.94-2.00 (m, 2H), 1.66-1.77 (m, 2H), 1.51 (d, J=16 Hz, 1H), 1.36-1.44 (m, 2H), 1.33 (s, 3H). MS (m/z) 432.2 (M+H+).

Provenance & Evidence