[C:1]([C:4]1[N:5]=[C:6]([C:24](O)([CH3:26])[CH3:25])[C:7]([O:11][C@@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1Cl)(=[O:3])[NH2:2].[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([CH:35]2[CH2:40][CH2:39][N:38]([C:41]3[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=3)[CH2:37][CH2:36]2)[CH2:31][CH2:30]1.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>O>[C:1]([C:4]1[N:5]=[C:6]([C:24]([CH3:26])=[CH2:25])[C:7]([O:11][C@@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]2)=[N:8][C:9]=1[NH:45][C:44]1[CH:46]=[CH:47][C:41]([N:38]2[CH2:39][CH2:40][CH:35]([N:32]3[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]3)[CH2:36][CH2:37]2)=[CH:42][CH:43]=1)(=[O:3])[NH2:2]A mixture of tert-butyl (3R)-3-{[5-carbamoyl-6-chloro-3-(2-hydroxypropan-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (300 mg), 4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (680 mg), diisopropylethylamine (400 μL), and N-methylpyrrolidone (1.2 mL) was reacted in a microwave reaction device at 180° C. for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1), and then washed with diisopropyl ether to obtain tert-butyl (3R)-3-{[5-carbamoyl-6-({-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (304 mg) as a yellow solid.
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