Reaction SMILES: OO.N1C2C(=CC=CC=2)C(=O)C1=O.[OH-].[Na+].Cl.FC1C=CC(F)=C(C(O)=O)C=1N.[F:29][C:30]1[CH:39]=[CH:38][C:37]([F:40])=[C:36]2[C:31]=1[C:32](=O)[NH:33][C:34]([CH3:41])=[N:35]2.P(Cl)(Cl)(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>O.C(OC(=O)C)(=O)C.P(Cl)(Cl)(Cl)=O.[Pd].C(O)(=O)C>[F:29][C:30]1[CH:39]=[CH:38][C:37]([F:40])=[C:36]2[C:31]=1[CH:32]=[N:33][C:34]([CH3:41])=[N:35]2
Reactant: Cc1nc2c(F)ccc(F)c2c(=O)[nH]1
Agent: [Pd]
Agent: Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CC(=O)OC(C)=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC(=O)O
Product: Cc1ncc2c(F)ccc(F)c2n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.2 %

Procedure:
A solution of 2.4 g (18.6 mmol) of 2,5-difluoroaniline in 11 ml of water and 1.6 ml of concentrated hydrochloric acid (37%) that is 50° C. and that was previously stirred for one hour at this temperature is added to a solution of 3.35 g (20.25 mmol) of chloral hydrate and 21.27 g (149.7 mmol) of sodium sulfate in 72 ml of water. It is stirred for another 30 minutes at room temperature, and after 4.09 g (58.9 mmol) of hydroxylammonium chloride in 19 ml of water is added over 45 minutes, it is heated to 125° C. and kept at this temperature for 5 minutes. After cooling and after another hour, the deposited light brown precipitate is filtered off, washed with water and dried. 3.0 g (15.0 mmol) of the hydroxylimine is obtained as an intermediate product that is dissolved in portions in 15 ml of concentrated sulfuric acid at 60° C. After addition is completed, it is heated for 2 hours to 80° C. and for 4 hours to 90° C. It is allowed to cool, and the solution is poured onto 100 g of ice. It is extracted with ethyl acetate, the organic phase is washed with water, dried on sodium sulfate and concentrated by evaporation. After chromatography on silica gel with hexane-ethyl acetate (0-45%), 1.2 g (7.1 mmol) of the 4,7-difluoroisatin is obtained. 1.8 ml of a 30% hydrogen peroxide solution is added in drops to isatin in 30 ml of a 1 molar sodium hydroxide solution over 10 minutes. After 2 hours of stirring at room temperature, it is cooled to 0° C., and 5 ml of a 4 molar hydrochloric acid is added and diluted with 50 ml of water. It is extracted with ethyl acetate, dried on sodium sulfate, concentrated by evaporation, and 1.27 g of 3,6-difluoroanthranilic acid, which is reacted without further purification, is thus quantitatively obtained. The 3,6-difluoroanthranilic acid is heated, in 8 ml of acetic acid anhydride for 45 minutes to 100° C. After cooling, the acetic acid that is produced and excess acetic acid anhydride are removed azeotropically with toluene in a vacuum. The residue is mixed with 40 ml of a 25% ammonia solution while being cooled with ice, and it is stirred for 72 hours. It is diluted with water and acidified with acetic acid. It is extracted with ethyl acetate, the organic phase is washed with water, dried on sodium sulfate and concentrated by evaporation. The thus obtained 1.03 g (5.25 mmol) of 5,8-difluoro-2-methyl-3H-quinazolin-4-one and 6 g of phosphorus pentachloride are heated in 20 ml of phosphoryl chloride over 12 hours to 125° C. After cooling, it is poured into saturated NaHCO3 solution and extracted with ethyl acetate. The organic phase is dried, and the solvent is removed. 1.7 g of 4-chloro-5,8-difluoro-2-methylquinazoline, which is dissolved in 60 ml of ethyl acetate and 5 ml of triethylamine, is obtained quantitatively. 600 mg of palladium on carbon is added and shaken for 2 hours (480 ml of hydrogen absorption) under a hydrogen atmosphere at normal pressure. Catalyst is removed from the solution by means of filtration on Celite, whereby it is rewashed with 100 ml of ethanol and concentrated by evaporation. After chromatography on silica gel with hexane-ethyl acetate-ethanol (0-40%), 550 mg of 5,8-difluoro-2-methylquinazoline is obtained. 890 mg (13.7 mmol) of sodium azide is added to 240 mg (1.3 mmol) of 5,8-difluoro-2-methylquinazoline, 300 mg (1.13 mmol) of 18-crown-6 in 10 ml of DMF, and the mixture is heated over 8 hours to 125° C. The solvent is removed in a vacuum, and it is chromatographed on silica gel with ethyl acetate, and 52 mg of product is obtained.