Trifluoroacetic acid → N-(2-Fluoro-4-iodo-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(2-trifluoromethyl-phenyl)-propionamide

Participants

Reaction Steps

Prepared by the same method as described in example 4 except that (i) (S)-2-tert-butoxycarbonylamino-3-(2-trifluoromethyl-phenyl)-propionic acid was used in place of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid in step 1, (ii) 2-fluoro-4-iodoaniline was used in place of 4-iodoaniline in step 2, (iii) the trifluoroacetic acid salt of (S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamide was isolated in step 3 and used directly in step 4 with 1.0 equivalent of triethylamine and (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride as the coupling reagent in place of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexaflurorophosphate, and (iv) after performing step 5, the diastereomers (resulting from racemization in step 2) of 2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamide were separated by chromatography over silica gel gradient eluted between 40 and 60% v/v ethyl acetate in hexane. The slower moving component was collected and after concentration in vacuo carried on to step 6.

Provenance & Evidence