Nitrogen → HCID 86731020, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (1S,3S,4S and 1R,3R,4R)-t-butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-3-cyanocyclohexane-1-carboxylate (Intermediate #47-4, 11 g, 33 mmol), 1-bromo-4-chlorobenzene (9.2 g, 48 mmol), KOAc (9.4 g, 96 mmol), Pd2(dba)3.CHCl3 (4.9 g, 5.0 mmol) and t-Butyl X-Phos (4.1 g, 10 mmol) in iso-propanol (100 mL) was degassed with bubbling N2 gas for 15 minutes and then stirred at 85° C. under nitrogen for 16 hours, and then concentrated in vacuo. The crude residue was purified by MPLC on Silica gel (eluting with 1-2% MeOH/DCM). Desired fractions were identified, combined, and concentrated in vacuo. The residue was further purified by reverse-phase preparative HPLC (using a gradient elution of 40-60% MeCN/water with 0.5% ammonia in 20) to afford the title compound. 1H NMR (400 MHz, CD3OD) δ 8.13 (s, 1H), 7.54 (d, J=9.2 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 4.32-4.30 (m, 1H), 3.49-3.42 (m, 1H), 2.51-2.47 (m, 2H), 2.20-2.13 (m, 3H), 1.95-1.82 (m, 1H), 1.66-1.59 (m, 1H), 1.50 (s, 9H). MS ESI: [M+H]+ m/z 444.

Provenance & Evidence