[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[N:15]=[C:16]([NH:19][C:20]4[CH:21]=[C:22]([CH2:26][CH2:27]OS(C)(=O)=O)[CH:23]=[CH:24][CH:25]=4)[N:17]=[CH:18][C:13]=3[CH:12]([CH3:33])[N:11]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[C:10]2=[O:42])[CH:6]=[CH:7][CH:8]=1)#[N:2].[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(OCC)(=O)C>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([N:11]2[CH:12]([CH3:33])[C:13]3[C:14](=[N:15][C:16]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][N:47]5[CH2:48][CH2:49][N:44]([CH3:43])[CH2:45][CH2:46]5)[CH:21]=4)=[N:17][CH:18]=3)[N:9]([C:5]3[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=3)[C:1]#[N:2])[C:10]2=[O:42])=[CH:39][CH:38]=1A mixture of (±)-methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester (0.10 g; 0.16 mmol) (from Example 5a supra) and 1-methylpiperazine (0.25 mL; 2.23 mmol) (Aldrich) and heated at 110° C. for 1 hour. Upon cooling, the mixture was diluted with ethyl acetate and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography (Biotage 12S; 100:0 to 40:60 ethyl acetate-methanol gradient) and then crystallized from ethyl acetate-hexanes to give (±)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile. (Yield 60.6 mg; 64.1%).
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