Sodium Bicarbonate → HCID 68098173, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromobenzo[d]isoxazol-3-amine (1.78 g, 8.36 mmol), (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (3.95 g, 8.99 mmol), Pd(Ph3P)4 (0.42 g, 0.364 mmol) and NaHCO3 (1.93 g, 23.0 mmol) was suspended in DME (60 mL) and H2O (20 mL) and the solution was degassed by evacuating and back-filling with N2 (repeated 5 times). The mixture was then heated at 70° C. overnight. LCMS indicated the reaction to be incomplete. A further portion of Pd(Ph3P)4 (0.10 g, 0.087 mmol) was added and heating continued for a further 12 h. The cooled reaction mixture was poured into H2O/EtOAc and the layers separated. The aq layer was extracted with EtOAc (×2) and the combined org layers were washed (H2O, brine), then dried (Na2SO4) and concentrated. The residue was purified by BIOTAGE® (TLC 5:4.5:0.5 hexane:EtOAc:MeOH) solvent A was 1:1 hex:EtOAc and solvent B was 20% MeOH in EtOAc to afford a red-orange foam (1.0 g). This material was purified by prep HPLC (CH3CN—H2O—NH4OAc) giving a light yellow foam (404.4 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ 11.85-12.21 (m, 1H), 7.85 (app t, J=8.0, 8.6, 2H), 7.72-7.73 (m, 4H), 7.54-7.60 (m, 2H), 6.41 (s, 2H), 4.76-4.83 (m, 1H), 3.54 (s, br, 1H), 3.31-3.37 (m, 1H, partially obscured by H2O), 2.14-2.25 (m, 1H), 1.79-2.04 (m, 3H), 1.40, 1.15 (s, 9H, rotamers). LCMS: Anal, Calcd. for C25H27N5O3: 445; found: 446 (M+H)+.

Provenance & Evidence