Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22].[CH3:24][C:25]([N:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)([CH3:28])[C:26]#[CH:27].C(N(CC)CC)C>CN(C=O)C.[Cu](Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:20][C:15]1[CH:14]=[C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([C:27]#[C:26][C:25]([CH3:28])([N:29]4[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]4)[CH3:24])=[C:3]([N+:21]([O-:23])=[O:22])[CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][C:16]=1[F:19]
Reactant: O=[N+]([O-])c1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1Cl
Reactant: C#CC(C)(C)N1CCN(C)CC1
Agent: Cl[Cu]Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN1CCN(C(C)(C)C#Cc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc2[N+](=O)[O-])CC1
Temperature: 140 °C
Yield: 37.4 %

Procedure:
A mixture (about 3:1, 52.0 g; described in Leonard et al., J. Org. Chem. 1975, 40, 356-363) of 7-chloro-6-nitro-3H-quinazolin-4-one and 7-chloro-8-nitro-3H-quinazolin-4-one and DMF (0.7 mL) were added to thionyl chloride (200 mL) and the mixture was heated under reflux for 4 hrs. The reaction mixture was concentrated to dryness and toluene (150 mL) was added. The mixture was concentrated further. This step was repeated twice and dichloromethane (280 mL) was added to the residue. The mixture was stirred at room temperature. To this suspension was added dropwise a solution (760 mL) of 3-chloro-4-fluoroaniline (36.9 g, 253.6 mmol) in isopropanol. Dichloromethane (300 mL) was added and the mixture was stirred, at 20° C. for 20 min. Hexane (600 mL) was added under ice-cooling, and stirring was continued at 20° C. The precipitate was collected by filtration, washed with hexane (200 mL×2) and dried under reduced pressure. The obtained solid was added to methanol (1 L)-water (120 mL), and triethylamine (30 mL) was added with stirring under ice-cooling. After stirring at room temperature for 1 hr, the precipitate was collected by filtration and washed with water (700 mL×2). The crudely purified substance (65 g) was suspension-washed with acetonitrile (1.2 L) with heating, and collected by filtration to give the objective (7-chloro-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine (54.6 g, 67%). 2) Nitrogen was passed through a solution (70 mL) of (7-chloro-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine (14.2 g. 40.1 mmol), 1-(1,1-dimethyl-2-propynyl)-4-methylpiperazine (4a) (10.0 g, 60.1 mmol), copper iodide (I) (380 mg), and tetrakis(triphenylphosphine)palladium (1.39 g) in DMF at 50° C. for 15 mm and triethylamine (13.9 mL, 100.0 mmol) was added and the mixture was stirred at an oil bath temperature of 140° C. for 50 mm. The reaction mixture was allowed to cool and concentrated. Aqueous sodium hydrogen carbonate (300 mL) was added, and the product was extracted with ethyl acetate (200 mL×2), dried and concentrated. The residue was subjected to silica gel column chromatography (chloroform-methanol; ethyl acetate-methanol) to give the objective nitro compound of (3-chloro-4-fluorophenyl)-{7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butynyl]-6-nitro-4-quinazolinyl}amine (3a) (7.25 g, 37%).