Morpholine → HCID 178433643, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-(4-bromophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one (69.1 mg, 0.167 mmol), morpholine (34.9 ml, 0.400 mmol) and sodium tert-butoxide (61.1 mg, 0.636 mmol) in Ianhydrous DMF (3 ml) was degassed by evaporating the flask under vacuum and refilling with nitrogen several times. Solid (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl [(S)-BINAP] (10.5 mg, 0.0169 mmol) and tris(dibenzylideneacetone)dipalladium(0) (7.6 mg, 0.0083 mmol) were added and the mixture was stirred at 80° C. under nitrogen for 47 h, adding more (S)-BINAP (10.7 mg, 0.172 mmol) and tris(dibenzylideneacetone)dipalladium(0) (7.9 mg, 0.0086 mmol) after 23 h. The solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel, 3-5% MoOH/CH2Cl2) and preparative HPLC (YMCSIL D column, 7% MeOH/1-chlorobutane) to give 17.9 mg (26%) of the title compound; mp 306-315° C. (CH2Cl2-MeOH-EtOAc); 1H NMR (360 MHz, DMSO-d6) δ2.27 (3H, s), 3.20 (4H, m), 3.77 (4H, m), 7.05 (2H, d, J8.8 Hz), 7.40 (2H, d), 7.42 (2H, d, J8.9 Hz), 8.15 (2H, d, J9.0 Hz), 8.51 (1H, s), 12.35 (1H, br s); MS (ES+) m/z 421/423[MH]+. Anal. found: C, 65.57; H, 4.84; N, 13.22. C23H21CIN4O2 requires: C, 65.63; H, 5.03; N, 13.31%.

Provenance & Evidence