Example 67
The stereoisomers of Example 66 (109 mg) prepared as described above are separated by HPLC using a chiral stationary phase to give 12.4 mg of stereoisomer 1 (Example 67) and 12.6 mg of stereoisomer 2 (Example 68).
Method for Separation:
HPLC apparatus type: Waters 600 Pump, 2767 Autosampler, UV Detector 2489; column: Daicel Chiralpak AS-H, 5.0 μm, 250 mm×20 mm; method: eluent hexane/ethanol 65:35; flow rate: 15 mL/min, temperature: 25° C.; UV Detection: 230 nm
Example 67: stereoisomer 1
[Figure (not displayed)]
Example 68: stereoisomer 2
[Figure (not displayed)]
Chiral HPLC
(Column Daicel Chiralpak
AS-H, eluent: hexane-
ethanol 70:30, 1 ml/min,HPLC-MS (MIL-
25° C.)01_007):
ExampleRt [min]Rt [min]MS (ESI pos): m/z
6714.553.00457
6821.352.98457
US10640486B2. Heteroarylcarboxamide derivatives as plasma kallikrein inhibitors (2020-05-05). Boehringer Ingelheim International GmbH [DE]. Inventors: Sara Frattini [IT], Remko Bakker [DE], Riccardo Giovannini [DE], Giacomo Fossati [IT], Dieter Hamprecht [AU], Iain Lingard [IT], Alexander Pautsch [DE], Bernd Wellenzohn [DE].