(4-Fluoro-3-((2-hydroxyethyl)carbamoyl)phenyl)boronic acid → 5-(2'-amino-1'-methyl-5'-oxo-2-phenyl-1',5'-dihydrospiro[chroman-4,4'-imidazole]-6-yl)-2-fluoro-N-(2-hydroxyethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

Pd(PPh3)2Cl2 (10 mg) in a 10 mL tube under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (20 mg, 0.052 mmol) in 1,4-dioxane (1 mL), Cs2CO3 (2 N, 0.3 mL) and 4-fluoro-3-(2-hydroxyethylcarbamoyl)phenylboronic acid (23 mg, 0.106 mmol). The mixture was heated at 120° C. in a microwave reactor for 0.5 h. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC to give pure 5-(2′-amino-1′-methyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)-2-fluoro-N-(2-hydroxyethyl)benzamide (3.1 mg, 12%). 1H-NMR (MeOD): 2.48 (m, 1H), 2.61 (m, 1H), 3.34 (s, 3H), 3.57 (m, 2H), 3.72 (m, 2H), 5.27 (d, 0.3H), 5.89 (d, 0.8H), 7.18 (m, 1H), 7.30 (m, 1H), 7.45 (m, 1H), 7.52 (m, 4H), 7.67 (m, 1H), 7.79 (m, 1H), 8.01 (m, 1H), 8.32 (m, 1H).

Provenance & Evidence