[C:1]1(C)C=CC(S(O)(=O)=O)=C[CH:2]=1.[NH2:12][C:13]1[N:17]([C:18]([NH2:20])=[O:19])[N:16]=[C:15]([CH3:21])[C:14]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[CH3:30].C(OC)(OC)(OC)C.O>C(#N)C>[CH3:29][O:28][C:25]1[CH:26]=[CH:27][C:22]([C:14]2[C:15]([CH3:21])=[N:16][N:17]3[C:18]([OH:19])=[N:20][C:1]([CH3:2])=[N:12][C:13]=23)=[C:23]([CH3:30])[CH:24]=1p-Toluenesulfonic acid (29.2 g, 154 mmol) in acetonitrile (100 mL) was added to the reaction mixture described in Example 3 containing 5-amino-4-(4-methoxy-2-methylphenyl)-3-methylpyrazole-1-carboxylic acid amide. The resulting mixture was heated to 85–90° C. and trimethyl orthoacetate (160 mL, 1.26 mol) was added over 5 minutes during the heating. The reaction was held for about 45 minutes in the desired range with a total of 1.5 hours of heating time from the initiation of the heating cycle. Reaction progress was monitored by HPLC. Water (1.50 L) was added over 5 minutes with a temperature drop to about 60° C. The resulting mixture was cooled to about 20° C. over 1 hour and the product isolated by filtration. The yield was 136 g (78.0% with a purity of 99.5 A %).
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