[F:1][C:2]1([F:7])[CH2:5][CH:4]([NH2:6])[CH2:3]1.Cl.CCN(C(C)C)C(C)C.[F:18][C:19]([F:42])([F:41])[C@H:20]1[CH2:25][CH2:24][C@H:23]([NH:26][C:27](=[O:40])[C:28]2[CH:33]=[C:32]([N+:34]([O-:36])=[O:35])[C:31]([NH:37][CH3:38])=[CH:30][C:29]=2F)[CH2:22][CH2:21]1>CC#N>[F:18][C:19]([F:41])([F:42])[C@H:20]1[CH2:25][CH2:24][C@H:23]([NH:26][C:27](=[O:40])[C:28]2[CH:33]=[C:32]([N+:34]([O-:36])=[O:35])[C:31]([NH:37][CH3:38])=[CH:30][C:29]=2[NH:6][CH:4]2[CH2:5][C:2]([F:7])([F:1])[CH2:3]2)[CH2:22][CH2:21]1A mixture of 3,3-difluoro-cyclobutylamine×HCl (49 mg, 0.34 mmol), DIPEA (0.26 ml, 1.5 mmol), N-(trans-4-trifluoromethyl-cyclohexyl)-2-fluoro-4-methylamino-5-nitro-benzoic acid amide (125 mg, 0.34 mmol, prepared according to WO2010/100249) and MeCN (5 mL) is stirred for 16 h at reflux. Then the mixture is concentrated, diluted with EtOAc, washed with water, concentrated, dried and directly used in the next step.
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