Reaction SMILES: [NH2:1][C:2]1[C:13]([Cl:14])=[CH:12][C:5]([O:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[C:4]([O:15][CH2:16][C:17]2[C:22]([O:23][CH3:24])=[CH:21][CH:20]=[C:19]([F:25])[C:18]=2[F:26])[CH:3]=1.C(N(CC)C(C)C)(C)C.[Cl:36][C:37]1[C:42]([N+:43]([O-:45])=[O:44])=[C:41](Cl)[N:40]=[C:39]([CH3:47])[N:38]=1.C(OCC)(=O)C>C(#N)C.O>[Cl:14][C:13]1[C:2]([NH:1][C:41]2[C:42]([N+:43]([O-:45])=[O:44])=[C:37]([Cl:36])[N:38]=[C:39]([CH3:47])[N:40]=2)=[CH:3][C:4]([O:15][CH2:16][C:17]2[C:22]([O:23][CH3:24])=[CH:21][CH:20]=[C:19]([F:25])[C:18]=2[F:26])=[C:5]([CH:12]=1)[O:6][CH2:7][C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)COc1cc(Cl)c(N)cc1OCc1c(OC)ccc(F)c1F
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(Cl)n1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COC(=O)COc1cc(Cl)c(Nc2nc(C)nc(Cl)c2[N+](=O)[O-])cc1OCc1c(OC)ccc(F)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.5 %

Procedure:
To a solution of methyl 2-[4-amino-5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-phenoxy]acetate (0.3 g) and N,N-diisopropylethylamine (0.14 mL) in acetonitrile (6 mL) was added 4,6-dichloro-2-methyl-5-nitropyrimidine (0.48 g) at −20° C., and the reaction mixture was allowed to warm slowly to room temperature, and stirred at room temperature overnight. To the reaction mixture were added ethyl acetate and water, and the resulting mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration, and the organic layer of the filtrate was separated. The organic layer was washed with 10% aqueous sodium chloride solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1) to give methyl 2-[5-chloro-4-(6-chloro-2-methyl-5-nitropyrimidin-4-ylamino)-2-(2,3-difluoro-6-methoxybenzyloxy)phenoxy]acetate (0.21 g). To this material were added 1,2-dimethoxyethane (10 mL), diethyl malonate (0.068 mL) and cesium carbonate (0.37 g), and the reaction vessel was equipped with a reflux condenser, and the mixture was stirred at 110° C. for 3 hours. The reaction mixture was cooled to room temperature. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1) to give diethyl 2-{6-[2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxycarbonyl-methoxyphenylamino]-2-methyl-5-nitropyrimidin-4-yl}malonate (0.13 g). This material was dissolved in dimethyl sulfoxide (3 mL). To the solution were added lithium chloride (63 mg) and water (13 mg), and the mixture was stirred at 100° C. overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. To the residue were added tetrahydrofuran (3 mL), methanol (3 mL) and 10% platinum-carbon powder (40 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/2−1/4−ethyl acetate/methanol=9/1−3/2) to give methyl 2-[4-(5-amino-2,6-dimethylpyrimidin-4-ylamino)-5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)phenoxy]acetate (21 mg). This material was suspended in tetrahydrofuran (3 mL). To the suspension was added triphosgene (6 mg) at room temperature. To the mixture was added sodium hydride (55%, 6 mg) under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: ethyl acetate−ethyl acetate/methanol=10/1) to give the title compound (14 mg).