nonane-4,6-dione

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42: 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42: 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: A stirred mixture of 4.88 g of 5-amino-3-methylpyrazole-4-carbonitrile and 6.25 g of 4,6-nonanedione in 50 ml of glacial acetic acid was heated at reflux for 10 hours. The reaction mixture after reflux was worked up as described in Example 50 to give 7.80 of 2-methyl-5,7-dipropylpyrazolo[1,5-a]pyrimidine-3-carbonitrile, mp 73°-74° C. was heated at reflux for 10 hours The reaction mixture after reflux

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

Procedure: 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared as follows: A mixture containing 15.6 g of 4,6-nonanedione, 200 ml of methanol, 10 g of cyanoacetamide and 6 g of sodium methoxide was refluxed with stirring for 22 hours and then stripped to dryness in vacuo. The residue was dissolved in 100 ml of water and the solution acidified with acetic acid. The white precipitate was collected, washed with water, air-dried, recrystallized from isopropyl alcohol-n-hexane and dried in vacuo at 80°-85° C. to produce 16.7 g of 3-cyano-4,6-di-n-propyl-2(1H)-pyridinone, m.p. 151°-152° C. 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared was refluxed The white precipitate was collected washed with water air-dried recrystallized from isopropyl alcohol-n-hexane dried in vacuo at 80°-85° C.

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

Procedure: 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared as follows: A mixture containing 15.6 g of 4,6-nonanedione, 200 ml of methanol, 10 g of cyanoacetamide and 6 g of sodium methoxide was refluxed with stirring for 22 hours and then stripped to dryness in vacuo. The residue was dissolved in 100 ml of water and the solution acidified with acetic acid. The white precipitate was collected, washed with water, air-dried, recrystallized from isopropyl alcohol-n-hexane and dried in vacuo at 80°-85° C. to produce 16.7 g of 3-cyano-4,6-di-n-propyl-2(1H)-pyridinone, m.p. 151°-152° C. 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared was refluxed The white precipitate was collected washed with water air-dried recrystallized from isopropyl alcohol-n-hexane dried in vacuo at 80°-85° C.

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42: 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: A stirred mixture of 4.88 g of 5-amino-3-methylpyrazole-4-carbonitrile and 6.25 g of 4,6-nonanedione in 50 ml of glacial acetic acid was heated at reflux for 10 hours. The reaction mixture after reflux was worked up as described in Example 50 to give 7.80 of 2-methyl-5,7-dipropylpyrazolo[1,5-a]pyrimidine-3-carbonitrile, mp 73°-74° C. was heated at reflux for 10 hours The reaction mixture after reflux

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

Procedure: A mixture of 4.48 g (0.02 moles) of 4-(5-amino-4H-1,2,4-triazol-3-yl)-1-piperazinecarboxylic acid, ethyl ester, 3.12 g (0.02 moles) of 4,6-nonanedione and 50 ml of glacial acetic acid was refluxed for 12 hours. The resulting solution was evaporated to dryness in vacuo. The residue was partitioned and treated as described in Example 12 and gave 6.77 g of the desired product as colorless crystals, mp 130°-132° C. was refluxed for 12 hours The resulting solution was evaporated to dryness in vacuo The residue was partitioned treated

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

Procedure: 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared as follows: A mixture containing 15.6 g of 4,6-nonanedione, 200 ml of methanol, 10 g of cyanoacetamide and 6 g of sodium methoxide was refluxed with stirring for 22 hours and then stripped to dryness in vacuo. The residue was dissolved in 100 ml of water and the solution acidified with acetic acid. The white precipitate was collected, washed with water, air-dried, recrystallized from isopropyl alcohol-n-hexane and dried in vacuo at 80°-85° C. to produce 16.7 g of 3-cyano-4,6-di-n-propyl-2(1H)-pyridinone, m.p. 151°-152° C. 3-Cyano-4,6-di-n-propyl-2(1H)-pyridinone was prepared was refluxed The white precipitate was collected washed with water air-dried recrystallized from isopropyl alcohol-n-hexane dried in vacuo at 80°-85° C.