[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)[CH2:3][CH:4]([NH2:15])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].O.[C:30]([C@@:38]([C:53]([OH:55])=[O:54])([OH:52])[C@@:39]([C:44](=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([OH:43])[C:40]([OH:42])=[O:41])(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([O-])(O)=O.[Na+].O=C(N1CCN2C(C(F)(F)F)=NN=C2C1)C[C@@H](N)CC1C=C(F)C(F)=CC=1F>CC(O)C.CO.C(OCC)(=O)C>[C:44]([C@@:39]([C:40]([OH:42])=[O:41])([OH:43])[C@@:38]([C:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([OH:52])[C:53]([OH:55])=[O:54])(=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.[O:1]=[C:2]([N:16]1[CH2:21][CH2:20][N:19]2[C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=[C:18]2[CH2:17]1)[CH2:3][CH:4]([NH2:15])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14]Dibenzoyl-L-tartaric acid salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was prepared by reacting 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1.0 mole) with Dibezoyl-L-tartaric acid monohydrate (1.18 molar equivalent) in IPA-methanol at 25-70° C. till solid mass precipitated out. The salt was filtered and washed with IPA; an enantiomerically enriched desired isomer was obtained. The salt was taken into ethyl acetate. It was basified with aq. NaHCO3. Ethyl acetate layer was separated and washed with water and brine solution. Ethyl acetate extract was collected and dried over anhydrous sodium sulfate. Ethyl acetate was distilled out to obtain a mixture of (2R) and (2S)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (% Purity by HPLC-98%; % Chiral purity by HPLC of R-isomer 70%).
Loading…