[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[C:20]([NH:22][CH3:23])[N:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].[Cl:24][C:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[C:27]([Cl:35])[C:26]=1[N:36]=[C:37]=[O:38].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[Cl:24][C:25]1[C:30]([C:31]([F:32])([F:34])[F:33])=[CH:29][CH:28]=[C:27]([Cl:35])[C:26]=1[NH:36][C:37](=[O:38])[N:22]([C:20]1[CH:21]=[C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([N:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:8][CH2:7]3)=[CH:14][CH:13]=2)[N:17]=[CH:18][N:19]=1)[CH3:23]This oil is re-dissolved in 2 ml of toluene and added portion-wise to a boiling solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-N′-methyl-pyrimidine-4,6-diamine (156 mg, 0.50 mmol; Example 145A) in 6 ml of toluene during 10 min. After 1.5 h, another 2 eq of 2,6-dichloro-3-trifluoromethyl-phenylisocyanate are added and stirring is continued for totally 2 h. Then the reaction mixture is diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; CH2Cl2/MeOH/NH3aq, 95:5:0.5) gives the title compound: ESI-MS: 568/570 [MH]+; tR=4.1 min (gradient J); TLC: Rf=0.3 (DCM/MeOH+1% NH3aq, 95:5).
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