Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:33]=[CH:32][C:22]([C:23]([NH:25][C@@H:26]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27]2)=[O:24])=[CH:21][C:20]=1[O:34][CH2:35][CH3:36].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH2:35]([O:34][C:20]1[CH:21]=[C:22]([CH:32]=[CH:33][C:19]=1[NH:18][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1)[C:23]([NH:25][C@@H:26]1[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27]1)=[O:24])[CH3:36]10-Chloro-6-methyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 10; 100 mg, 0.39 mmol), 4-amino-3-ethoxy-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide (Intermediate 166; 104 mg, 0.39 mmol) and 4-toluenesulphonic acid monohydrate (187 mg, 0.98 mmol) were heated in 4-methyl-2-pentanol (3 mL) at 140° C. for 3 hours. The cooled reaction mixture was absorbed on to an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by base modified preparative reverse phase HPLC to yield the title compound as a white solid (114 mg, 61%).
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