Cl.[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:18][C@@H:19]([N:23]3[CH2:27][CH2:26][C@H:25]([NH:28][S:29]([C:32]4[S:36][C:35]([N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)=[N:34][CH:33]=4)(=[O:31])=[O:30])[C:24]3=[O:42])[C:20]([OH:22])=[O:21])=[C:10]([O:13][C:14]([F:17])([F:16])[F:15])[CH:11]=2)[CH:6]=[CH:5][N:4]=1.C(=O)([O-])[O-].[K+].[K+].[C:49](=[O:60])([O:53][CH:54]1[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]1)[O:50][CH2:51]Cl.[I-].[K+]>CN(C=O)C.O>[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:18][C@@H:19]([N:23]3[CH2:27][CH2:26][C@H:25]([NH:28][S:29]([C:32]4[S:36][C:35]([N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)=[N:34][CH:33]=4)(=[O:31])=[O:30])[C:24]3=[O:42])[C:20]([O:22][CH2:51][O:50][C:49]([O:53][CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)=[O:60])=[O:21])=[C:10]([O:13][C:14]([F:15])([F:17])[F:16])[CH:11]=2)[CH:6]=[CH:5][N:4]=1To a solution of (2R)-3-[1-amino-7-(trifluoromethoxy)isoquinolin-6-yl]-2-[(3S)-2-oxo-3-({[2-(pyrrolidin-1-yl)-1,3-thiazol-5-yl]sulfonyl}amino)pyrrolidin-1-yl]propanoic acid hydrochloride (compound of example 4) (0.5 g, 0.73 mmol) in anhydrous DMF (3 ml) were added potassium carbonate (0.3 g, 2.2 mmol) and chloromethyl cyclohexyl carbonate (0.21 g, 1.1 mmol), followed by potassium iodide (12 mg, 0.07 mmol). The reaction mixture was stirred at room temperature under nitrogen for 12 hours, and then was poured onto cold water, the resulting precipitate was filtered of, washed with water and dried under P2O5.
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