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The 4,5-dichloro-1-indanone is prepared as in Example 15 for the preparation of 6,7-dichloro-1-indanone but star6ing with 26 g of 3-(2,3-dichlorophenyl)propionic acid, 138 ml of thionyl chloride, 550 ml of anhydrous dichloromethane and 20.5 g of aluminium chloride. After recrystallization from 100 ml of boiling ethanol, 12.67 g of 4,5-dichloro-1-indanone are thus obtained which melt at 78 C.
The propionic acid 2.7 g. (0.011 mole) was suspended in benzene (27 ml.) and treated with 1.7 g. of thionyl chloride (0.014 mole) and dimethyl formamide (two drops). The reaction was refluxed for thirty minutes, filtered and evaporated to give 3-(2,3-dichlorophenyl)propionyl chloride which was dissolved in chlorobenzene (12 ml.) and treated with anhydrous aluminum chloride 2.4 g. (18 mmoles). The reaction was stirred for one hour and poured onto ice. The chlorobenzene was evaporated in vacuo and the residue was extracted with chloroform which was washed, dried over sodium sulfate and evaporated to give 4,5-dichloro-1-indanone.
<Step 2> Synthesis of 4,5-dichloro-2,3-dihydro-1H-inden-1-one To a solution of the compound (0.90 g) obtained in (Example 19) <Step 1> in dichloromethane (15 mL), oxalyl chloride (0.42 mL) and N,N-dimethylformamide (one drop) were added and the resultant reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloroethane (10 mL). To the reaction mixture, aluminum chloride (0.55 g) was added and the resultant reaction mixture was heated to reflux for 1 hour. The reaction mixture was poured into ice water, followed by extracting the reaction mixture with ethyl acetate. The organic phase was washed with a saturated aqueous sodium bicarbonate and saturated saline and was dried over anhydrous sodium sulfate. From the organic phase, the solvent was distilled off under reduced pressure and the resultant residue was purified by silica gel column chromatography (eluate: n-hexane:ethyl acetate=100:0 to 95:5 to 90:10) to obtain the subject compound (310 mg) as a yellow solid.
N'-(4,5-dichloro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethylethane-1,2-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56%
General procedure: To a solution of 6,7-dichlorobenzofuran-3(2H)-one (20) (1.0 g, 4.95 mmol) in a mixed solvent of THF (10 mL), MeOH (18.2 mL) and AcOH (1.8 mL) was added N,N-dimethylethane-1,2-diamine (0.703 mL, 6.44 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 h and then stirred at 45-50 C for 2 h. To the mixture was added 2-picoline borane complex (695 mg, 6.50 mmol) at room temperature. The mixture was stirred at room temperature for 14 h. After concentration under reduced pressure, the residue was diluted with 2 M HCl (40 mL, 80 mmol) and the mixture was stirred at room temperature for 20 min. Insoluble was filtered off, and the filtrate was diluted with EtOAc/n-hexane (1:1,40 mL). The aqueous layer of the filtrate was made alkaline with 8 M NaOH (10 mL, 80 mmol) and 2M NaOH (2.0 mL, 4.0 mmol). The resulting alkaline aqueous solution was extracted with EtOAc (3 × 50 mL). The combined organic layer was washed with brine (100 mL) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure to give (±)-16 (626 mg, 46%) as a brown oil
(±)-N-(4,5-dichloro-2,3-dihydro-1H-inden-1-yl)-N-(2-(dimethylamino)ethyl)-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide[ No CAS ]
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