Potassium Carbonate → 2-Amino-3-(3'-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]-imidazo[5,1-f][1,2,4]triazin-7-yl}-1,1'-biphenyl-4-yl)propanoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (Example 9) (40 mg, 0.085 mmol), 4-(dihydroxyboryl)phenylalanine (57.6 mg, 0.275 mmol), tetrakis(triphenylphosphine) palladium (0) (15.0 mg, 0.013 mmol) and potassium carbonate (52.8 mg, 0.382 mmol) was added DME (1.8 mL) and distilled water (0.6 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 130° C. for a total time of 1.5 hours. After cooling to room temperature, removed solvent under reduced pressure, dissolved residue in methanol (25 mL), and added silica gel (1 g). Following evaporation of the volatiles under reduced pressure, the pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using dichloromethane:methanol (100:0 to 65:35) followed by ethyl acetate:methanol (80:20) using a RediSep silica gel cartridge (12 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 2-amino-3-(3′-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]-imidazo[5,1-f][1,2,4]triazin-7-yl}-1,1′-biphenyl-4-yl)propanoic acid (0.0199 g) as a yellow solid. 1H NMR (DMSO-d6): δ9.63 (s, 1H), 9.26 (s, 1H), 8.55 (s, 1H), 8.45 (d, J=7.9 Hz, 1H), 7.73 (d, J=8.1 Hz, 1H), 7.61-7.21 (m, 5H), 7.09 (s, 2H), 3.65 (s, 6H), 3.63 (s, 3H), 3.43-3.12 (m, 1H), 2.92-2.80 (m, 2H). MS m/z 555 (M+1).

Provenance & Evidence