2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 86709780, compound

Participants

Reaction Conditions

Reaction Steps

(4R)-tert-Butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (124 mg, 0.212 mmol), dicyanozinc (Aldrich, St. Louis, Mo.; 32.4 mg, 0.276 mmol), Pd2(dba)3 (Aldrich, St. Louis, Mo.; 9.71 mg, 10.61 μmol), and XPhos (Strem, Newburyport, Mass.; 10.11 mg, 0.021 mmol) in a mixture of DMF (2.0 mL) and water (0.020 mL) was heated at 100° C. for 19 h. The mixture was concentrated onto silica gel and chromatographically purified (ISCO, 12 g silica gel column, 0-60% EtOAc/hexanes, 15 min, 254 nm) to provide (4R)-tert-butyl 4-(6-(5-cyano-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (102.8 mg, 0.194 mmol, 91% yield) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ ppm 9.04 (1 H, s), 8.74 (1 H, br. s.), 8.25 (1 H, br. s.), 8.02 (1 H, s), 7.78 (1 H, s), 7.64 (1 H, s), 5.84 (1 H, d, J=6.8 Hz), 4.63 (1 H, br. s.), 4.35-4.44 (1 H, m), 4.21-4.33 (1 H, m), 3.90-4.10 (2 H, m), 3.73-3.85 (2 H, m), 3.34 (2 H, d, J=14.1 Hz), 2.53-2.70 (2 H, m), 2.45 (1 H, m), 2.09-2.30 (2 H, m), 1.68-1.90 (4 H, m), 1.14 (9 H, br. s.). MS (ESI, pos. ion) m/z: 531.3 (M+1).

Provenance & Evidence