[NH2:1][C:2]1[N:3]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:4]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[CH:6]=1.C([O-])(O)=O.[Na+].C(Cl)(Cl)=O.[N-]=C=O.C(C1C=C(N[C:41]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([O:54][C:55]3[CH:60]=[CH:59][N:58]=[C:57]([NH:61][CH2:62][CH:63]4[CH2:65][CH2:64]4)[N:56]=3)=[CH:46][CH:45]=2)=[O:42])N(C)N=1)(C)(C)C>C(Cl)Cl.C1(C)C=CC=CC=1.C1COCC1>[C:7]([C:5]1[CH:6]=[C:2]([NH:1][C:41]([NH:43][C:44]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]([O:54][C:55]3[CH:60]=[CH:59][N:58]=[C:57]([NH:61][CH2:62][CH:63]4[CH2:65][CH2:64]4)[N:56]=3)=[CH:46][CH:45]=2)=[O:42])[N:3]([C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:4]=1)([CH3:10])([CH3:9])[CH3:8]3-Amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole (2.39 g, 9.00 mmol, 1 equiv.) was dissolved in 35 mL methylene chloride and 35 mL saturated aqueous NaHCO3 was added. The biphasic mixture was stirred until all solids had completely dissolved and was then cooled to 0° C. The organic layer was then treated with phosgene in one portion via syringe while not stirring (15.8 mL of a 20% solution toluene, 31.5 mmol, 3.5 equiv.). The resulting mixture was stirred vigorously at 0° C. for 1 h. The organic layer was separated, dried (Na2SO4) and filtered. The methylene chloride was removed in vacuo and the resulting isocyanate in toluene was treated with a solution of aminonaphthyl-chloropyrimidyl ether intermediate (see Example 4) (2.45 g, 9.0 mmol, 1.0 equiv.) in 40 mL anhydrous THF. The mixture was stirred at room temperature for 3.5 h, then the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel using 0–10% MeOH in methylene chloride eluent mixtures, followed by recrystallization from ether, providing 1.90 g (40%) of the urea intermediate.
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