Diphenylphosphinic chloride → rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-2-fluoro-phenyl)-amide

Participants

Reaction Steps

In a manner similar to the method described in Example 27, rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid prepared in Example 4 (0.53 g, 0.92 mmol), was reacted with diisopropylethylamine (0.95 g, 7.4 mmol), diphenylphosphinic chloride (0.87 g, 3.7 mmol), then reacted with 4-amino-3-fluorobenzonitrile (Matrix) (0.13 g, 0.92 mmol) in 1,2-dichloroethane at 70° C. to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-2-fluoro-phenyl)-amide as a off white solid (Yield 0.14 g, 26%).

Provenance & Evidence