2-oxopentanoic acid

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: In the manner given in Example 9, 7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine can be stirred with α-oxopentanoic acid at room temperature to give 7-chloro-2-[(1-carboxybutylidene)hydrazino]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.

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

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

Procedure: To a stirred and cooled (0° C.) mixture of 9 parts of 4-[1-(1H-imidazol-1-yl)-2-methylpropyl]-1,2-benzenediamine in 80 parts of acetic acid and 20 parts of water were added 5 parts of 2-oxopentanoic acid. The reaction mixture was stirred for 12 hours at room temperature. The whole was poured into ice water and neutralized with a sodium hydroxide solution 3N. The product was extracted three times with 130 parts of dichloromethane. The combined extracts were dried, filtered and evaporated. For obtaining 6-[1-(1H-imidazol-1yl)-2-methylpropyl]-3-propyl-2(1H)-quinoxalinone, the residue was purified by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-butanone and 1,1'-oxybisethane. The precipitated product was filtered off and stirred in cold 4-methyl-2-pentanone. After filtration, the product was recrystallized from a mixture of methanol and 2-propanone, yielding 1.6 parts (13.2%) of the above product; mp. 259.7° C. (comp. 100). cooled The reaction mixture was stirred for 12 hours at room temperature The product was extracted three times with 130 parts of dichloromethane The combined extracts were dried filtered evaporated

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

Procedure: To a stirred and cooled (0° C.) mixture of 9 parts of 4-[1-(1H-imidazol-1-yl)-2-methylpropyl]-1,2-benzenediamine in 80 parts of acetic acid and 20 parts of water were added 5 parts of 2-oxopentanoic acid. The reaction mixture was stirred for 12 hours at room temperature. The whole was poured into ice water and neutralized with a sodium hydroxide solution 3N. The product was extracted three times with 130 parts of dichloromethane. The combined extracts were dried, filtered and evaporated. For obtaining 6-[1-(1H-imidazol-1yl)-2-methylpropyl]-3-propyl-2(1H)-quinoxalinone, the residue was purified by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-butanone and 1,1'-oxybisethane. The precipitated product was filtered off and stirred in cold 4-methyl-2-pentanone. After filtration, the product was recrystallized from a mixture of methanol and 2-propanone, yielding 1.6 parts (13.2%) of the above product; mp. 259.7° C. (comp. 100). cooled The reaction mixture was stirred for 12 hours at room temperature The product was extracted three times with 130 parts of dichloromethane The combined extracts were dried filtered evaporated

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

Procedure: A solution of 1.74 g (15 mmole) of 2-ketovaleric acid and 1.13 g (10 mmole) of 2,2-dimethylcyclopropanecarboxamide in 20 ml of toluene was refluxed with stirring with collection of H2O in a small Dean-Stark trap. After 20 hrs. the solution was cooled and treated with a gentle stream of N2. Before much of the solvent had evaporated, crystallization was induced by scratching. After standing, the solid was collected on a filter and washed with toluene and some Et2O. Yield of white crystals=0.63 g (30%), mp 154.5°-155.5° (slight prelim. softening). Tlc (4:1 toluene-AcOH) showed only an extremely faint trace of the other isomer. NMR was consistent with the Z-configuration. the solution was cooled Before much of the solvent had evaporated crystallization the solid was collected on a filter washed with toluene

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

Procedure: In the manner given in Example 9, 7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine can be stirred with α-oxopentanoic acid at room temperature to give 7-chloro-2-[(1-carboxybutylidene)hydrazino]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.

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

Procedure: In the manner given in Example 9, 7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine can be stirred with α-oxopentanoic acid at room temperature to give 7-chloro-2-[(1-carboxybutylidene)hydrazino]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.

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

Procedure: 8.8 g benzyl prolinate hydrochloride, 9.78 g dicyclohexylcarbodiimide and 6.12 g diisopropylethylamine were reacted together in 50 mL dichloromethane at 0°. 5.51 g 2-oxopentanoic acid in 10 mL dichloromethane was added dropwise at 0°. The pH of the reaction was adjusted to between 8 and 9 with diisopropylethylamine. The reaction mixture was stirred for four hours at 0°, then room temperature overnight. The next day, the reaction mixture was filtered, concentrated to dryness, and partitioned between ethyl acetate and water. The organic layer was washed with 5% sodium bisulfate, 5% sodium bicarbonate, and saturated sodium chloride solutions, and dried with magnesium sulfate. The organic layer was concentrated to give a yellow oil. The oil was then passed through a silica gel column and eluted with ethyl acetate/hexane (4:6) and ethyl acetate/hexane (1:1). Benzyl N-(2-oxopentanoyl)prolinate, [α]D25 -56.9, was isolated. room temperature overnight The next day, the reaction mixture was filtered concentrated to dryness partitioned between ethyl acetate and water The organic layer was washed with 5% sodium bisulfate, 5% sodium bicarbonate, and saturated sodium chloride solutions dried with magnesium sulfate The organic layer was concentrated to give a yellow oil eluted with ethyl acetate/hexane (4:6) and ethyl acetate/hexane (1:1)

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

Procedure: 8.8 g benzyl prolinate hydrochloride, 9.78 g dicyclohexylcarbodiimide and 6.12 g diisopropylethylamine were reacted together in 50 mL dichloromethane at 0°. 5.51 g 2-oxopentanoic acid in 10 mL dichloromethane was added dropwise at 0°. The pH of the reaction was adjusted to between 8 and 9 with diisopropylethylamine. The reaction mixture was stirred for four hours at 0°, then room temperature overnight. The next day, the reaction mixture was filtered, concentrated to dryness, and partitioned between ethyl acetate and water. The organic layer was washed with 5% sodium bisulfate, 5% sodium bicarbonate, and saturated sodium chloride solutions, and dried with magnesium sulfate. The organic layer was concentrated to give a yellow oil. The oil was then passed through a silica gel column and eluted with ethyl acetate/hexane (4:6) and ethyl acetate/hexane (1:1). Benzyl N-(2-oxopentanoyl)prolinate, [α]D25 -56.9, was isolated. room temperature overnight The next day, the reaction mixture was filtered concentrated to dryness partitioned between ethyl acetate and water The organic layer was washed with 5% sodium bisulfate, 5% sodium bicarbonate, and saturated sodium chloride solutions dried with magnesium sulfate The organic layer was concentrated to give a yellow oil eluted with ethyl acetate/hexane (4:6) and ethyl acetate/hexane (1:1)

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