2-(dimethylaminomethylidene)cyclohexane-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Cyclohexanedione (11.2 g, 100 mmol) was suspended in dimethylformamide dimethylacetal (28 mL) and the mixture was heated at reflux for 1 h. The mixture was cooled to room temperature and the solvent was evaporated to provide an orange solid, which was recrystallized from ethyl acetate to provide 12 g (72%) of 2-dimethylaminomethylene-1,3-cyclohexanedione as light orange needles, mp 116°-118° C.; 1H NMR (CDCl3) δ8.05 (s, 1H), 3.40 (s, 3H), 3.19 (s, 3H), 2.26 (t, 4H), 1.95 (m, 1H). the mixture was heated at reflux for 1 h the solvent was evaporated to provide an orange solid, which was recrystallized from ethyl acetate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A MeOH solution of methylhydrazine 0.046 g (0.01 mol) and 2-dimethylaminomethylene-cyclohexane-1,3-dione 1.67 g (0.01 mol) was stirred at room temperature for 1 h, and then was stirred at 50° C. for 1 h. NMR of crude material indicated the reaction was completed. Work up: The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried with MgSO4, and the solvent was rotary evaporated. The crude product was filtered through silica gel, and 1.03 g pure product was obtained, the yield is 69%. washed with brine The organic phase was dried with MgSO4 The crude product was filtered through silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A MeCN solution of cyclohexane-1,3-dione 2.24 g (0.02 mol) i and DMF-DMA 11.9 g (0.1 mol) was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the product was used for the next step with no purification. The solvent was removed under reduced pressure the product was used for the next step with no purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A MeCN solution of cyclohexane-1,3-dione 2.24 g (0.02 mol) i and DMF-DMA 11.9 g (0.1 mol) was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the product was used for the next step with no purification. The solvent was removed under reduced pressure the product was used for the next step with no purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-hydroxyethyl hydrazine (1.36 mL, 20 mmol) was slowly added to an ice-cooled solution of 2-((dimethylamino)methylene)cyclohexane-1,3-dione (3.34 g) in methanol (50 mL). After stirring at room temperature for 20 min, the solvent was evaporated. Flash chromatography (SiO2, EtOAc/MeOH=100:5 to 100:7 to 100:10) gave the title compound as a white solid. B. Preparation of 1-(2-(tert-butyldimethylsilyloxy)ethyl)-6,7-dihydro-1H-indazol-4(5H)-one. the solvent was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Solution of 3-(tert-butyldiphenylsilyloxy) propanamidine (25 g, 77 mmol) and 2-((dimethylamino)methylene)cyclohexane-1,3-dione (12.8 g, 77 mmol) in 400 mL of dry EtOH was heated at 80° C. for 3 h. After cooling to room temperature, the solvent was evaporated. Flash chromatography (SiO2, EtOAc/hexane=1:1) gave the title compound as a white solid. the solvent was evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A MeOH solution of methylhydrazine 0.046 g (0.01 mol) and 2-dimethylaminomethylene-cyclohexane-1,3-dione 1.67 g (0.01 mol) was stirred at room temperature for 1 h, and then was stirred at 50° C. for 1 h. NMR of crude material indicated the reaction was completed. Work up: The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried with MgSO4, and the solvent was rotary evaporated. The crude product was filtered through silica gel, and 1.03 g pure product was obtained, the yield is 69%. washed with brine The organic phase was dried with MgSO4 The crude product was filtered through silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A MeCN solution of cyclohexane-1,3-dione 2.24 g (0.02 mol) i and DMF-DMA 11.9 g (0.1 mol) was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the product was used for the next step with no purification. The solvent was removed under reduced pressure the product was used for the next step with no purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ethanol suspension (60 ml) of 10.73 g (40 mmol) of 1-amidino-4-benzylpiperazine sulfate, were added an ethanol solution (80 ml) of 1.6 g (40 mmol) of sodium hydroxide and then 6.69 g (40 mmol) of the 2-dimethylaminomethylenecyclohexane-1,3-dione obtained in Referential Example 46. The resultant mixture was heated under reflux for 4 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off. The residue was added with 100 ml of water and then extracted twice with 200 ml of ethyl acetate. The ethyl acetate layer was washed with saturated saline and then dried with anhydrous magnesium sulfate. Ethyl acetate was the distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=3/7) to obtain 9.90 g of the intended product as light yellowish crystals (yield: 77%).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ethanol suspension (60 ml) of 10.73 g (40 mmol) of 1-amidino-4-benzylpiperazine sulfate, were added an ethanol solution (80 ml) of 1.6 g (40 mmol) of sodium hydroxide and then 6.69 g (40 mmol) of the 2-dimethylaminomethylenecyclohexane-1,3-dione obtained in Referential Example 46. The resultant mixture was heated under reflux for 4 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off. The residue was added with 100 ml of water and then extracted twice with 200 ml of ethyl acetate. The ethyl acetate layer was washed with saturated saline and then dried with anhydrous magnesium sulfate. Ethyl acetate was the distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=3/7) to obtain 9.90 g of the intended product as light yellowish crystals (yield: 77%).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice-cold solution of 67 grams of 2-dimethylaminomethylene-1,3-cyclohexanedione in 600 ml of methanol was added slowly a solution of 21.3 ml of methylhydrazine in 200 ml of methanol and the resulting solution was heated at reflux for 2 hours. The solvent was removed under reduced pressure and the residue was triturated with ethyl ether to give 1,5,6,7-tetrahydro-1-methyl-4H-indazol-4-one as a tan crystalline solid melting at about 88°-91° C. the resulting solution was heated at reflux for 2 hours The solvent was removed under reduced pressure the residue was triturated with ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture was prepared from 90 grams of 1,3-cyclohexanedione and 225 ml of N,N-dimethylformamide dimethyl acetal and heated at reflux for 90 minutes. Excess solvent was removed under reduced pressure and the residue was triturated in hot ethyl acetate to give 2-dimethylaminomethylene-1,3-cyclohexanedione as rust colored crystals melting at about 114.5°-116° C. heated at reflux for 90 minutes Excess solvent was removed under reduced pressure the residue was triturated in hot ethyl acetate