C([C:4]1[C:13]2[C:8](=[C:9]([NH:14][C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[O:16])[CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][N:5]=1)(O)=O.C1(P([N:43]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.O>O1CCOCC1>[NH2:43][C:4]1[C:13]2[C:8](=[C:9]([NH:14][C:15]([NH:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=3)=[O:16])[CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][N:5]=1A mixture of N-(1-carboxyisoquinolin-5-yl)-N′-[4-(trifluoromethyl)benzyl]urea (Example 117, 309 mg, 0.794 mmol), diphenylphosphoryl azide (210 μl, 0.975 mmol) and triethylamine (210 μl, 1.50 mmol) in 1,4-dioxane (25 ml) was heated at 100° C., under a nitrogen atnosphere for 1.5 h. Water (0.25 ml) was then added and the reaction mixture heated for a further 1 hour. The reaction mixture was then cooled to room temperature, filtered and the filtrate evaporated. The residue was purified using a Bond-Elut SCX ion-exchange cartridge, first eluting non-basic materials with methanol, then eluting the product with 2M methanolic ammonia. The basic fractions were evaporated and further purified by flash column chromatography (eluant 5% MeOH-95% dichloromethane increasing to 10% MeOH-90% dichloromethane). The product was then passed through a second SCX purification to give the title compound (77 mg, 27%). m/z (ES+) 361 (M+H)+.
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