C(O[C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:14]2[N:19]=[CH:18][C:17]([N:20]3[CH2:24][CH2:23][N:22]([CH3:25])[C:21]3=[O:26])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:42][CH3:43])=O)(C)(C)C.[ClH:44].CCO[C:48]([CH3:50])=[O:49].FC(F)(F)C1C=[C:55](C=C(C(F)(F)F)C=1)[CH2:56][N:57]([C:65]1[N:70]=[CH:69][C:68](N2CCN(C)C2=O)=C[N:66]=1)[C@@H:58]1CN[C@H](CC)C1.CCN(CC)CC.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(Cl)Cl>[F:36][C:34]([F:35])([F:37])[C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([C:38]([F:40])([F:41])[F:39])[CH:31]=1)[CH2:27][N:13]([C@H:11]1[CH2:10][C@@H:9]([CH2:42][CH3:43])[N:8]([C:6]2[C:68]([Cl:44])=[CH:69][N:70]=[C:65]([N:57]3[CH2:58][CH2:50][CH:48]([OH:49])[CH2:55][CH2:56]3)[N:66]=2)[CH2:12]1)[C:14]1[N:19]=[CH:18][C:17]([N:20]2[CH2:24][CH2:23][N:22]([CH3:25])[C:21]2=[O:26])=[CH:16][N:15]=1To a mixture of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.24 mmol) in EtOAc (1 mL) is added 4N HCl/EtOAc (2.4 mL, 2.44 mmol). After removal of solvent, the mixture is used without further purification. (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine is treated with 2,4,5-trichloro-pyrimide (67.1 mg, 0.37 mmol) and Et3N (0.07 mL, 0.49 mmol) in CH2Cl2 (1 mL) at RT for 12 hours. After adding sat. NaHCO3 (aq.), the mixture is extracted with CH2Cl2, washed with brine and dried (MgSO4). Concentration under vacuum and purification with silica gel column chromatography (eluent: n-hexane:EtOAc=1:1) gives 1-[2-((3,5-Bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one (110 mg, 68%)
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