Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:20])[C:7](=[O:19])[CH2:8][CH2:9][N:10]2[CH:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:37]=[CH:36][C:25]([C:26]([NH:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:27])=[CH:24][C:23]=1[O:38][CH3:39].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>CC(C)CC(O)C.CO>[CH3:39][O:38][C:23]1[CH:24]=[C:25]([CH:36]=[CH:37][C:22]=1[NH:21][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:20])[C:7](=[O:19])[CH2:8][CH2:9][N:10]2[CH:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])=[CH:4][N:3]=1)[C:26]([NH:28][CH:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)=[O:27]10-chloro-6-methyl-2-(2-oxocyclopentyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 261; 58 mg, 0.19 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 53 mg, 0.20 mmol) and p-toluene sulphonic acid monohydrate (80 mg, 0.42 mmol) were dissolved in 4-methyl-2-pentanol (2 mL) and heated by microwave irradiation at 150° C. for 30 minutes. After cooling, the reaction mixture was dissolved in methanol (5 mL) and water (5 mL) and poured directly onto an SCX-3 cartridge (5 g). The cartridge was washed with methanol (50 mL), before elution of products with 2M ammonia in methanol (50 mL). The ammoniacal fraction was evaporated and the residue was purified by base modified reverse phase preparative HPLC to yield the title compound as a yellow solid (11 mg, 7%).
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