propanediamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Sodium hydride (900 g, 57.5% dispersion in mineral oil; 518 g active NaH; 22.5M) was stirred with 7.5 L toluene in a 22 L round-bottomed flask. Butanol was added over 5 hr. so that the pot temperature was maintained at 40°. The mixture was stirred an additional 16 hr. Malonamide (765 g; 7.5 M) was added, followed by ethyl trifluoroacetate (1065 g; 7.5 M). The ensuing reaction was exothermic; the mixture was then heated on a steam-bath for 3.5 hrs. It was then stirred at 23°-25° for an additional 16 hrs. The mixture was extracted with water (1×4 L and 1×2 L). The combined aqueous extracts were treated with activated charcoal and filtered. The filtrate was maintained at 10°-15° as it was acidified to pH 1-2 with 37% hydrochloric acid. The mixture was chilled to 5°. The solid was isolated by filtration and dried at 50° in vacuo to give 600 g (44.4% yield) VI m.p. 255°-256° (Lit. 265°). so that the pot temperature was maintained at 40° The ensuing reaction the mixture was then heated on a steam-bath for 3.5 hrs It was then stirred at 23°-25° for an additional 16 hrs The mixture was extracted with water (1×4 L and 1×2 L) The combined aqueous extracts were treated with activated charcoal filtered The filtrate was maintained at 10°-15° as it The mixture was chilled to 5° The solid was isolated by filtration dried at 50° in vacuo

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

Procedure: A mixture of compound 1,3-dimethylpyrimidine-2,4(1H,3H)-dione (14 g, 0.1 mol), malonamide (45 g, 0.44 mol) and sodium ethoxide (34 g, 0.4 mol) in EtOH (500 mL) was refluxed for 20 mins. The mixture was cooled to r.t, quenched by water and acidified with 1 M HCl to pH=1-2. The solid was filtered and the filter cake was concentrated in vacuo to afford compound 2,6-dihydroxynicotinamide. (10 g, yield: 65%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 7.90-7.88 (d, 1H), 5.66-5.64 (d, 1H). was refluxed for 20 mins The mixture was cooled quenched by water The solid was filtered the filter cake was concentrated in vacuo

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

Procedure: 4-(Trimethylsilanylmethoxy)benzaldehyde (obtained in step 1 of Example 1) (10.4 g, 0.005 mol) and malonamide (5.5 g, 0.055 mol) in 20 ml of dry toluene in the presence of 0.5 ml of piperidine and 0.3 g of acetic acid are refluxed for 3 hours in a reactor equipped with Dean-Stark apparatus. The water formed is removed azeotropically. The mixture is cooled and the organic phase is washed twice with water. The organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated off under vacuum. After recrystallization from ethanol, 7.2 g (yield: 49%) of the derivative of Example 10 are obtained in the form of an off-white powder: equipped with Dean-Stark apparatus is removed azeotropically The mixture is cooled the organic phase is washed twice with water The organic phase is dried over sodium sulfate filtered the solvent is evaporated off under vacuum After recrystallization from ethanol, 7.2 g (yield: 49%) of the derivative of Example 10 are obtained in the form of an off-white powder

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methoxide (74 g, 1.37 mol) was dissolved in methanol (1,000 mL), and malon diamide (100 g, 0.979 mol) was added to this solution at room temperature. To this mixture, 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (191 g, 1.14 mol) was added dropwise at a temperature between 25 and 30° C., and the resultant mixture was refluxed under heating for 2 hours. After cooling to 45° C., concentrated hydrochloric acid was added to the mixed solution to give a pH of 3 to 4, and 500 mL of methanol was distilled off at normal pressure. To the residue, water (500 mL) was added, and the mixture was stirred for a day at room temperature. The resultant product was precipitated while cooling with ice. Thus obtained crystal was collected by filtration, washed with water, and then dried under reduced pressure, to obtain 167 g of a subject compound (yield: 83%). under heating for 2 hours was distilled off at normal pressure To the residue, water (500 mL) was added The resultant product was precipitated while cooling with ice Thus obtained crystal was collected by filtration washed with water dried under reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(3,4-Dichlorophenoxy)-3-dimethylaminopropenal (13 g), malonamide (5.6 g), and t-BuOK (6.2 g) were mixed in 50 ml of DMSO and heated at 45° C. for 30 minutes. This mixture was then stirred at room temperature for an additional 24 hours after which it was poured into 200 g of an ice-water mixture and acidified with concentrated HCl. A solid formed which was collected by centrifugation, vacuum dried, and recrystallized from 2-propanol to give 6.5 g of the desired 5-(3,4-dichlorophenoxy)-2-hydroxy-3-pyridinecarboxamide, m.p. 246°-249° C. A solid formed which was collected by centrifugation, vacuum dried recrystallized from 2-propanol

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

Procedure: 0.33 g (14.4 mmol) of sodium were dissolved in 50 ml of methanol, 3.16 g (12.03 mmol) of 1-butoxy-4-chloro-4,5,5,5-tetrafluoropent-1-en-3-one and 1.27 g (12.03 mmol) of malonamide were added and the mixture was heated under reflux for 7 h. The mixture was concentrated, and 1N hydrochloric acid was then added. The resulting precipitate was filtered off with suction and dried. This gave 380 mg (12% of theory) of a yellowish powder. the mixture was heated under reflux for 7 h The mixture was concentrated 1N hydrochloric acid was then added The resulting precipitate was filtered off with suction dried

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

Procedure: 0.33 g (14.4 mmol) of sodium were dissolved in 50 ml of methanol, 3.16 g (12.03 mmol) of 1-butoxy-4-chloro-4,5,5,5-tetrafluoropent-1-en-3-one and 1.27 g (12.03 mmol) of malonamide were added and the mixture was heated under reflux for 7 h. The mixture was concentrated, and 1N hydrochloric acid was then added. The resulting precipitate was filtered off with suction and dried. This gave 380 mg (12% of theory) of a yellowish powder. the mixture was heated under reflux for 7 h The mixture was concentrated 1N hydrochloric acid was then added The resulting precipitate was filtered off with suction dried

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

Procedure: 0.53 g (22.8 mmol) of sodium were dissolved in 50 ml of methanol, 5.0 g (19.0 mmol) of 1-butoxy-5-chloro-4,4,5,5-tetrafluoropent-1-en-3-one and 2.0 g (19.0 mmol) of malonamide were then added and the mixture was heated under reflux for 6 h. The mixture was concentrated, and 1N hydrochloric acid was then added. The resulting precipitate was filtered off with suction and dried. This gave 3.8 g (73% of theory) of a brownish powder. the mixture was heated under reflux for 6 h The mixture was concentrated 1N hydrochloric acid was then added The resulting precipitate was filtered off with suction dried

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

Procedure: 0.22 g (9.7 mmol) of sodium was dissolved in 50 ml of ethanol, 2 g (8.1 mmol) of 1-butoxy-4,4,5,5,5-pentafluoropent-1-en-3-one and 0.86 g (8.1 mmol) malonamide were added and the mixture was heated under reflux for 7 h. The mixture was concentrated, and 1N hydrochloric acid was added. The resulting precipitate was filtered off with suction and dried. This gave 1.9 g (94% of theory) of a yellow powder. the mixture was heated under reflux for 7 h The mixture was concentrated 1N hydrochloric acid was added The resulting precipitate was filtered off with suction dried

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

Procedure: 0.22 g (9.7 mmol) of sodium was dissolved in 50 ml of ethanol, 2 g (8.1 mmol) of 1-butoxy-4,4,5,5,5-pentafluoropent-1-en-3-one and 0.86 g (8.1 mmol) malonamide were added and the mixture was heated under reflux for 7 h. The mixture was concentrated, and 1N hydrochloric acid was added. The resulting precipitate was filtered off with suction and dried. This gave 1.9 g (94% of theory) of a yellow powder. the mixture was heated under reflux for 7 h The mixture was concentrated 1N hydrochloric acid was added The resulting precipitate was filtered off with suction dried