4-Chlorophenylboronic acid → 18-[4-(4'-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl]-17-cyclohexyl-1,4,11-triazatricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

Participants

Reaction Conditions

Reaction Steps

A saturated solution of NaHCO3 (1 mL) was added to a solution of 9 (20 mg, 0.029 mmol), 4-chlorobenzeneboronic acid (11 mg, 0.068 mmol) and bis(triphenyl-phosphine)palladium (II) chloride (4 mg, 0.0063 mmol) in dimethoxyethane (DME; 6 mL). The resulting solution was heated at 73° C. for 8 h. Then, the reaction mixture was successively cooled down to room temperature, partitioned between water and ethyl acetate, dried (Na2SO4) and evaporated. Purification by column chromatography (CH2Cl2/methanol, 97:3) afforded the target product contaminated with impurities. The product was further purified by trituration in methanol, then filtered off to give the target product 10: m/z=704 (M+H)+. NMR (DMSO-d6): δ (ppm) 1.23-1.33 (m, 6H), 1.42-1.53 (m, 8H), 1.67-1.77 (m, 2H), 1.87-2.02 (m, 2H), 2.80 (m, 1H, CH cyclohexyl), 3.15 (m, 4H, 2×CH2NHCO), 3.83 (s, 3H, OCH3), 4.44 (s, 2H, CH2CONH), 5.00 (s, 2H, CH2O), 7.04-7.09 (m, 3H), 7.23 (d, J=2.6 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.40-7.47 (m, 7H), 7.76 (d, J=8.4 Hz, 1H), 7.93 (s, 1H), 8.30 (broad s, 1H, NH), 8.51 (broad s, 1H, NH).

Provenance & Evidence