N-methyl-2-pyrrolidone → HCID 71227465, compound

Participants

Reaction Steps

A solution of 1-ethyl-5-methyl-1H-pyrazol-4-amine, 2 hydrochloride (0.5 g, 2.52 mmol), Boc2O (0.703 ml, 3.03 mmol), TEA (1.055 mL, 7.57 mmol) and DMAP (10 mg, 0.082 mmol) in DCM (18.74 mL) was stirred at RT for 16 h. The mixture was then extracted with DCM, dried over Na2SO4 and filtered. The filtrate was concentrated and purified via silica gel chromatography (ISCO, 40 g column; 0-5% MeOH/DCM) to give tert-butyl (1-ethyl-5-methyl-1H-pyrazol-4-yl)carbamate as brown oil (300 mg, 52.8% yield). To a solution of tert-butyl (1-ethyl-5-methyl-1H-pyrazol-4-yl)carbamate (0.162 g, 0.719 mmol) in THF (1 mL) at −78° C. under N2 was added n-BuLi (2.5M in hexane) (0.27 ml, 0.675 mmol) dropwise. The mixture was allowed to warm up to RT and stirred for 20 min. 1-{[(3S,5S)-5-methyl-1-oxaspiro[2.5]oct-5-yl]methyl}-1H-benzimidazole-6-carbonitrile (0.15 g, 0.533 mmol) was then added followed by NMP (0.5 mL). The solution was then heated at 70° C. for 16 h. Water was then added to the reaction mixture and extracted with EtOAc. The organic layer was concentrated and purified via HPLC to give 1-(((5S,7S)-3-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white solid (89.6 mg, 38.9% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.38 (s, 1H), 7.83 (d, J=8.28 Hz, 1H), 7.59 (dd, J=1.51, 8.28 Hz, 1H), 7.41 (s, 1H), 4.16 (br. s., 2H), 4.03 (q, J=7.03 Hz, 2H), 3.54 (s, 2H), 2.14 (s, 3H), 1.95 (d, J=14.0 Hz, 1H), 1.86 (d, J=14.31 Hz, 1H), 1.61 (d, J=13.55 Hz, 3H), 1.31-1.51 (m, 3H), 1.28 (t, 3H), 1.06 (s, 3H). MS (m/z) 433.3 (M+H+).

Provenance & Evidence