Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](C(=O)CC(OC)=O)=[C:7]([C:12]([O:14][CH3:15])=[O:13])[N:8]2[CH3:11])=[CH:4][CH:3]=1.ClC(=O)CC(OC)=O>ClCCCl.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[N:8]2[CH3:11])=[CH:4][CH:3]=1
Reactant: COC(=O)CC(=O)c1c(C(=O)OC)n(C)c2cc(F)ccc12
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: COC(=O)CC(=O)Cl
Solvent: ClCCCl
Product: COC(=O)c1cc2ccc(F)cc2n1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 10 %

Procedure:
A 60% suspension of 7.9 g (197 mmol) of sodium hydride (washed with petroleum ether beforehand) and 36.1 g (176 mmol) of methyl 6-fluoro-1H-indole-2-carboxylate (containing 10 to 20% of ethyl 6-fluoro-1H-indole-2-carboxylate) in 250 ml of N,N-dimethylformamide is stirred at ambient temperature for 2 h. Then 12 ml (193 mmol) of iodomethane in 50 ml of N,N-dimethylformamide are added and the mixture is stirred at ambient temperature for 12 h. The contents are poured into an ice/water mixture. Dichloromethane is added and the aqueous phase is neutralized with hydrochloric acid (1N). The organic phase is separated off, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column in a mixture of solvents (cyclohexane/dichloromethane: 50/50 to 0/100 then dichloromethane/ethyl acetate: 100/0 to 70/30). 32.7 g (170 mmol) are isolated of a white compound of methyl 6-fluoro-1-methyl-1H-indole-2-carboxylate containing 10 to 20% of ethyl 6-fluoro-1-methyl-1H-indole-2-carboxylate. 1.2. methyl 3-[6-fluoro-2-(methoxycarbonyl)-1-methyl-1H-indol-3-yl]-3-oxopropanoate In portions, 6.5 ml (60 mmol) of methyl 3-chloro-3-oxo-propanoate are added to a solution of 6.6 ml (60 mmol) of titanium tetrachloride in 80 ml of 1,2-dichloro-ethane. The mixture is stirred at ambient temperature for 30 minutes. A solution of 5 g (24.1 mmol) of methyl 6-fluoro-1-methyl-1H-indole-2-carboxylate (containing 10 to 20% of ethyl 6-fluoro-1-methyl-1H-indole-2-carboxylate), obtained in step 1.1., is added and the mixture is stirred at 40° C. for 20 h. The mixture is poured into ice water and extracted with dichloromethane. The organic phase is separated off, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column (eluent: cyclohexane/dichloromethane: 90/10 to 0/100 then dichloromethane/ethyl acetate 100/0 to 50/50). This gives 13 g of a pasty solid containing primarily the compound. It is used as it is in the rest of the synthesis. 1.3 N,N-dimethyl-3-[6-fluoro-2-(methoxycarbonyl)-1-methyl-1H-indol-3-yl]-3-oxopropanamide A stream of gaseous dimethylamine is passed into a mixture of 13 g (44.4 mmol) of methyl 3-[6-fluoro-2-(methoxycarbonyl)-1-methyl-1H-indol-3-yl]-3-oxo-propanoate, obtained in step 1.2., and 0.2 g (1.63 mmol) of 4-(N,N-dimethyl)aminopyridine in 80 ml of toluene. Immediately a condenser, surmounted by a balloon flask, is fitted and the solution is stirred at 100° C. for 20 h. The mixture is cooled to ambient temperature and concentrated under reduced pressure. 200 ml of dichloromethane, water and hydrochloric acid (1N) are added. The organic phase is separated off, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column (eluent: cyclohexane/dichloromethane: 50/50, then dichloromethane/ethyl acetate 100/0 to 0/100). 4.6 g (14 mmol) are isolated of a yellow solid, which is used as it is in the rest of the synthesis. 1.4 7-fluoro-N,N,5-trimethyl-4-oxo-3-(pyrid-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide A solution of 1.4 g (4.1 mmol) of N,N-dimethyl-3-[6-fluoro-2-(methoxycarbonyl)-1-methyl-1H-indol-3-yl]-3-oxopropanamide, obtained in step 1.3., in 40 ml of absolute ethanol is heated at reflux for 22 h with a few drops of glacial acetic acid and 1.4 g (12.8 mmol) of 2-pyridylhydrazine. The mixture is cooled and concentrated under reduced pressure. Water and 200 ml of dichloromethane are added. Sodium hydroxide solution is added to a pH>10. The organic phase is separated off, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column in a mixture of solvents (dichloromethane/ethyl acetate: 100/0 to 0/100, then ethyl acetate/methanol: 100/0 to 90/10). The product obtained is subsequently chromatographed on a neutral alumina column in a mixture of solvents (dichloromethane/ethyl acetate: 100/0 to 0/100, then ethyl acetate/methanol: 100/0 to 90/10). This gives a solid, which is rinsed with diethyl ether. 0.25 g (0.66 mmol) of compound is isolated in the form of a white solid. Melting point: 222-223° C.; M+H+: 380.