6-methylheptane-2,4-dione

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of cyanothioacetamide (2.20 g, 22 mmol) and 6-methyl-2,4-heptanedione (3.12 g, 22 mmol) in anhydrous EtOH (40 mL) was added triethylamine (0.4 mL) and the reaction was heated at 50° C. for 1 h before it was allowed to cool to room temperature. Filtration and washing of the precipitates with EtOH gave 6-isobutyl-2-mercapto-4-methylnicotinonitrile as a yellow solid (2.8 g, 61%). to cool to room temperature Filtration washing of the precipitates with EtOH

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of cyanothioacetamide (2.20 g, 22 mmol) and 6-methyl-2,4-heptanedione (3.12 g, 22 mmol) in anhydrous EtOH (40 mL) was added triethylamine (0.4 mL) and the reaction was heated at 50° C. for 1 h before it was allowed to cool to room temperature. Filtration and washing of the precipitates with EtOH gave 6-isobutyl-2-mercapto-4-methylnicotinonitrile as a yellow solid (2.8 g, 61%). to cool to room temperature Filtration washing of the precipitates with EtOH

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of cyanothioacetamide (2.20 g, 22 mmol) and 6-methyl-2,4-heptanedione (3.12 g, 22 mmol) in anhydrous EtOH (40 ML) was added triethylamine (0.4 mL) and the reaction was heated at 50° C. for 1 h before it was allowed to cool to room temperature. Filtration and washing of the precipitates with EtOH gave 6-isobutyl-2-mercapto-4-methylnicotinonitrile as a yellow solid (2.8 g, 61%). to cool to room temperature Filtration washing of the precipitates with EtOH

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add a solution of 6-methylheptane-2,4-dione (5.0 g, 35.16 mmol) in tetrahydrofuran (50 mL) dropwise to a cooled suspension (0° C.) of sodium hydride (1.69 g, 42.2 mmol, 60% dispersion in oil) in tetrahydrofuran (50 mL). After 1 hr., add bromoacetic acid ethyl ester (4.28 mL, 38.68 mmol) dropwise and stir at 0° C. to room temperature over 88 hr. Partition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL). Separate the organic layer, dry (sodium sulfate), filter and concentrate. Purify using silica gel chromatography (95:5 hexanes:ethyl acetate) to give 3-acetyl-6-methyl-4-oxoheptanoic acid ethyl ester (5.81 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 4.10 (m, 4H), 2.81 (d, 2H), 2.41 (t, 1H), 2.22 (s, 3H), 1.23 (m, 4H), 0.92 (m, 6H). Partition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL) Separate the organic layer dry (sodium sulfate) filter concentrate Purify

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 0.1 mol sodium hydride was added 100 ml anhydrous tetrahydrofuran, then added slowly dropwise 0.1 mol 6-methyl-2,4-heptandione at room temperature. The reaction was stirred for 0.5 hours, then 0.12 mol iodomethane was added dropwise and the reaction was stirred at room temperature for further 10 hours. Upon completing the reaction, 20 ml water was added. The mixture was extracted with ethyl acetate. After removing the solvent, distillation under reduced pressure gave a cut fraction 88-9° C./1 kPa (165-166° C. at atmosphere pressure), and the yield was 94%. the reaction was stirred at room temperature for further 10 hours was added The mixture was extracted with ethyl acetate After removing the solvent, distillation under reduced pressure gave a cut fraction 88-9° C./1 kPa (165-166° C. at atmosphere pressure)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add a solution of 6-methylheptane-2,4-dione (5.0 g, 35.16 mmol) in tetrahydrofuran (50 mL) dropwise to a cooled suspension (0° C.) of sodium hydride (1.69 g, 42.2 mmol, 60% dispersion in oil) in tetrahydrofuran (50 mL). After 1 hr., add bromoacetic acid ethyl ester (4.28 mL, 38.68 mmol) dropwise and stir at 0° C. to room temperature over 88 hr. Partition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL). Separate the organic layer, dry (sodium sulfate), filter and concentrate. Purify using silica gel chromatography (95:5 hexanes:ethyl acetate) to give 3-acetyl-6-methyl-4-oxoheptanoic acid ethyl ester (5.81 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 4.10 (m, 4H), 2.81 (d, 2H), 2.41 (t, 1H), 2.22 (s, 3H), 1.23 (m, 4H), 0.92 (m, 6H). Partition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL) Separate the organic layer dry (sodium sulfate) filter concentrate Purify

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 0.1 mol sodium hydride was added 100 ml anhydrous tetrahydrofuran, then added slowly dropwise 0.1 mol 6-methyl-2,4-heptandione at room temperature. The reaction was stirred for 0.5 hours, then 0.12 mol iodomethane was added dropwise and the reaction was stirred at room temperature for further 10 hours. Upon completing the reaction, 20 ml water was added. The mixture was extracted with ethyl acetate. After removing the solvent, distillation under reduced pressure gave a cut fraction 88-9° C./1 kPa (165-166° C. at atmosphere pressure), and the yield was 94%. the reaction was stirred at room temperature for further 10 hours was added The mixture was extracted with ethyl acetate After removing the solvent, distillation under reduced pressure gave a cut fraction 88-9° C./1 kPa (165-166° C. at atmosphere pressure)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from (2-Amino-5-bromo-phenyl)-phenyl-methanone [example A16] and 6-methyl-2,4-heptanedione according to the procedure of example 1. Yield: 55%. MS: m/z=381 (M).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from (2-Amino-5-bromo-phenyl)-phenyl-methanone [example A16] and 6-methyl-2,4-heptanedione according to the procedure of example 1. Yield: 9%. MS: m/z=381 (M).

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To aminoguanidine hydrochloride (1.59 g, 14.4 mmol), water (5 ml), sodium hydroxide (576 mg, 14.4 mmol), and 6-methyl-2,4-heptanedione (manufactured by Tokyo Chemical Industry, purity: 97.0% or higher) (4.50 g, 31.6 mmol) were added, and then stirred at 80° C. for 8 hours. To the reaction mixture, water (30 ml) was added, and the extraction was carried out with ethyl acetate (10 ml). The extract was washed with saturated brine, dried with anhydrous sodium sulfate, and then concentrated. The obtained residue (3.83 g) was subjected to silica gel column chromatography (80 g of silica gel, chloroform to chloroform:methanol=100:1) to obtain 4-isobutyl-2-(3-isobutyl-5-methylpyrazol-1-yl)-6-methylpyrimidine (181 mg, 4%) and 4-isobutyl-2-(5-isobutyl-3-methylpyrazol-1-yl)-6-methylpyrimidine (2.05 g, 50%). the extraction The extract was washed with saturated brine dried with anhydrous sodium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: According to the same manner as that described in Reference Example 6, 2-amino-3',4',4,5-tetramethoxybenzophenone hydrochloride was reacted with 6-methyl-2,4-heptanedione to give 4-(3,4-dimethoxyphenyl)-3-isovaleryl-6,7-dimethoxy-2-methylquinoline. This compound was recrystallized from ethyl acetate-hexane to give colorless prisms. mp. 135°-137° C.

反応条件: temp:-11.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.20 mol (15.21 g) hydroxy urea were dissolved in 300 ml of M HCl, 300 ml of methanol were added, and 0.20 mol (28.44 g) 6-methyl-2,4-heptanedione were added dropwise while cooling at −12 to −10° C. The solution was allowed to warm slowly to room temperature and stirred over night, then evaporated to dryness. The residue was suspended with 200 ml of acetone, the mixture cooled to below 0° C. in an ice/ethanol bath, the solid filtered off and washed with a little ice-cold acetone. After drying 7.23 g of a product was obtained, which contained 58% of the title compound and 42% of the by-product ammonium chloride. were added to warm slowly to room temperature evaporated to dryness the mixture cooled to below 0° C. in an ice/ethanol bath the solid filtered off washed with a little ice-cold acetone After drying 7.23 g of a product was obtained