1-Hydroxybenzotriazole → HCID 86619923, compound
Reaction equation
Cl.[F:2][C:3]([F:29])([F:28])[CH2:4][O:5][C:6]([N:8]1[CH2:14][C@H:13](N)[C:12](=[O:16])[N:11]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:10]2[CH:22]=[C:23](F)[C:24](F)=[CH:25][C:9]1=2)=[O:7].OC(C)(C(NCC(F)(F)C(F)(F)F)=O)C(O)=O.ON1C2C=CC=CC=2N=N1>>[F:29][C:3]([F:2])([F:28])[CH2:4][O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:16])[N:11]([CH2:17][C:18]([F:19])([F:20])[F:21])[C:10]2[CH:22]=[CH:23][CH:24]=[CH:25][C:9]1=2)=[O:7]Participants
Procedure
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)+.
Workup
- customyielded a 1
- customThe two epimers were separated by HPLC on a chiral phase (Chiralpak AD)
Sources & evidence
- ORD record
- ord-0e4963f41b0d4c7cab83531da9605ea2
- Source dataset
- uspto-grants-2008_08
- Patent number
- US07414049B2
Reaction notes
Loading…