1-Hydroxybenzotriazole → HCID 86619923, compound

Participants

Reaction Steps

In an analogous procedure to that described in Example 1e) the condensation of (S)-3-amino-7,8-difluoro-4-oxo-5-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid 2,2,2-trifluoro-ethyl ester hydrochloride and (RS)-2-hydroxy-2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid with 1-hydroxy-benzotriazole and N-(3-dimethylaminpropyl)-N′-ethyl-carbodiimide hydrochloride as the condensating agents yielded a 1:1-mixture of the epimeric title compounds as a white foam; MS (m/e): 669 (M+H)+. The two epimers were separated by HPLC on a chiral phase (Chiralpak AD) using a 4:1-mixture of heptane and isopropanol as the eluent yielding the first eluting epimer (−)-(S)-7,8-difluoro-3-[(R or S)-2-hydroxy-2-(2,2,3,3,3-pentafluoro-propylcarbamoyl)-propionylamino]-4-oxo-5-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid 2,2,2-trifluoro-ethyl ester as a light yellow solid [MS (m/e): 669 (M+H)+] and the second eluting epimer (−)-(S)-7,8-difluoro-3-[(S or R)-2-hydroxy-2-(2,2,3,3,3-pentafluoro-propylcarbamoyl)-propionylamino]-4-oxo-5-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carboxylic acid 2,2,2-trifluoro-ethyl ester as a light yellow foam; MS (m/e): 669 (M+H)+.

Provenance & Evidence