3-benzylpentane-2,4-dione

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

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-hydrazino-6-pyridin-2-yl-[1,3,5]triazin-2-ylamine (5.25 g, 25.6 mmol), 3-benzylpentane-2,4-dione (5.0 g, 28.4 mmol), and p-toluenesulfonic acid monohydrate (0.475 g, 2.50 mmol) in dimethylsulfoxide (50 mL) was heated to 75° C. for 20 hours. The reaction mixture was allowed to cool to room temperature, and the suspension was dissolved in methylene chloride (700 mL). The solution was washed three times with water, once with brine, dried (magnesium sulfate), and concentrated to afford a moist solid. The crude product was suspended in ethyl acetate (50 mL), heated to reflux, allowed to cool to room temperature, and filtered (repeated three times). The final product was obtained as a white solid containing 3% dimethylsulfoxide by weight: 8.63 g (90%). 1H NMR (CDCl3) δ 8.84-8.53 (m, 1H), 8.48 (d, J=7.9 Hz, 1H), 7.86-7.91 (m, 1H), 7.46-7.50 (m, 1H), 7.13-7.30 (m, 5H), 6.61 (br s, 1H), 6.40 (br s, 1H), 3.83 (s, 2H), 2.79 (s, 3H), 2.24 (s, 3H) ppm. MS (ESI) m/z 358 (M+H+). to cool to room temperature The solution was washed three times with water once with brine, dried (magnesium sulfate) concentrated to afford a moist solid heated to reflux to cool to room temperature filtered (repeated three times)

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

Procedure: To a solution of sodium ethoxide (freshly prepared from sodium hydride (0.474 g, 19.8 mmol) and anhydrous ethanol (50 mL)) was added pentane-2,4-dione (6.00 g, 60.0 mmol). The resulting mixture was heated to 50° C. while a solution of benzyl bromide (3.42 g, 20 mmol) in ethanol (20 mL) was added over 30 minutes. The reaction was then heated to reflux. After 2 hours, the mixture was concentrated, and the residue was dissolved in ethyl acetate, washed three times with water, once with brine, dried (magnesium sulfate) and concentrated to afford an oil. Flash chromatography over silica (ethyl acetate/dichloromethane) afforded 3.13 g (82%) of a colorless oil. The proton spectrum showed the product exists as equal parts of the keto and enol tautomers: 1H NMR (CDCl3) δ 16.81 (s, 0.5H), 7.13-7.32 (m, 5H), 4.00 (t, J=7.6 Hz, 0.5H), 3.65 (s, 1H), 3.14 (d, J=7.6 Hz, 0.5H), 2.06-2.13 (m, 6H) ppm. was added over 30 minutes The reaction was then heated to reflux the mixture was concentrated the residue was dissolved in ethyl acetate washed three times with water once with brine, dried (magnesium sulfate) concentrated to afford an oil

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

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 1 from 3-benzylpentane-2,4-dione and 2-(4-hydrazinophenyl)ethanol hydrochloride: 1H-NMR (CDCl3) δ 7.39-7.15 (9H, m), 3.89-3.85 (2H, t, J=6.4 Hz), 3.48 (2H, s), 2.91 (2H, t, J=6.6 Hz), 2.29 (3H, s), 2.21 (3H, s).

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

Procedure: Boric anhydride (0.49 g, 7.0 mmol) was combined with 3-benzyl-2,4-pentanedione (8, 1.90 g, 10.0 mmol) and stirred for 48 hr at room temperature under a nitrogen atmosphere. A solution of dry ethyl acetate (10 ml), benzaldehyde (1b, 2.05 ml, 20.2 mmol) and tributyl borate (11.0 ml, 40.5 mmol) was added and the mixture stirred for 15 min at room temperature. Butylamine (0.20 ml, 2.0 mmol) was added dropwise over 30 min and stirring was continued for 18 hr at room temperature. Hydrochloric acid (15 ml, 0.4 N) was warmed to 60° C., added to the mixture and stirring was continued for 1 hr. The resulting mixture was filtered to afford a solid. The crude solid was triturated with methanol to give 2.30 g (63%) of a yellow solid: mp 162-164° C. [expected mp 156-158° C.]; 1H NMR: δ 3.99 (s, 2H), 6.99 (d, 2H, J=15.6 Hz), 7.34 (m, 15H), 7.77 (d, 2H, J=15.2 Hz); 13C NMR: δ 31.8, 109.3, 120.8, 126.5, 127.8, 128.1, 128.8, 130.0, 135.3, 140.5, 141.9, 183.6. the mixture stirred for 15 min at room temperature stirring was continued for 18 hr at room temperature added to the mixture stirring was continued for 1 hr The resulting mixture was filtered to afford a solid The crude solid was triturated with methanol

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

Procedure: Boric anhydride (0.49 g, 7.0 mmol) was combined with 3-benzyl-2,4-pentanedione (8, 1.90 g, 10.0 mmol) and stirred for 48 hr at room temperature under a nitrogen atmosphere. A solution of dry ethyl acetate (10 ml), benzaldehyde (1b, 2.05 ml, 20.2 mmol) and tributyl borate (11.0 ml, 40.5 mmol) was added and the mixture stirred for 15 min at room temperature. Butylamine (0.20 ml, 2.0 mmol) was added dropwise over 30 min and stirring was continued for 18 hr at room temperature. Hydrochloric acid (15 ml, 0.4 N) was warmed to 60° C., added to the mixture and stirring was continued for 1 hr. The resulting mixture was filtered to afford a solid. The crude solid was triturated with methanol to give 2.30 g (63%) of a yellow solid: mp 162-164° C. [expected mp 156-158° C.]; 1H NMR: δ 3.99 (s, 2H), 6.99 (d, 2H, J=15.6 Hz), 7.34 (m, 15H), 7.77 (d, 2H, J=15.2 Hz); 13C NMR: δ 31.8, 109.3, 120.8, 126.5, 127.8, 128.1, 128.8, 130.0, 135.3, 140.5, 141.9, 183.6. the mixture stirred for 15 min at room temperature stirring was continued for 18 hr at room temperature added to the mixture stirring was continued for 1 hr The resulting mixture was filtered to afford a solid The crude solid was triturated with methanol

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

Procedure: 3-Benzylidene-2,4-pentanedione (7, 6.50 g, 34.5 mmol) and palladium on activated carbon (0.25 g, 10%) were combined in ethyl acetate (50 ml). The mixture was placed under a hydrogen atmosphere (60 psi) on a Parr apparatus for 4 hr at room temperature. The resulting mixture was filtered through celite and the solvent evaporated to afford an oil. The crude oil was distilled bulb to bulb to give 6.52 g (99%) of a clear oil; 1H NMR: δ enol form: 2.02 (s, 6H), 3.62 (s, 2H), 7.24 (m, 5H); keto form: 2.07 (s, 6H), 3.11 (d, 2H, J=7.4 Hz), 4.01 (t, 1H, J=7.7 Hz), 7.24 (m, 5H); 13C NMR: δ 22.9, 29.4, 32.5, 33.8, 69.2, 107.9, 125.9, 126.3, 127.0, 128.1, 128.2, 137.7, 139.3, 191.4, 202.9. for 4 hr at room temperature The resulting mixture was filtered through celite the solvent evaporated to afford an oil The crude oil was distilled bulb to bulb

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution containing 6.3 g of 3-benzyl-2,4-pentanedione in 50 ml of dichloromethane was gradually added 5.3 g of bromine in 20 ml of dichloromethane under cooling (0°-5° C.). The solution was stirred for 10 min. at 0° C. and the solvent evaporated in vacuo. The residue was dissolved in 100 ml of pyridine and refluxed for 30 min. Pyridine was evaporated in vacuo, the residue was dissolved in dichloromethane and washed first with 6M hydrochloric acid and then with 2.6M NaOH. The solvent was evaporated and the residue distilled in vacuo. Bp 186°-188° C./16 mm, yield 1.2 g. under cooling (0°-5° C.) the solvent evaporated in vacuo The residue was dissolved in 100 ml of pyridine refluxed for 30 min Pyridine was evaporated in vacuo the residue was dissolved in dichloromethane washed first with 6M hydrochloric acid The solvent was evaporated the residue distilled in vacuo

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

Procedure: To a solution containing 5.5g of potassium tert-butoxide in 50ml of DMSO was added 6.0 g of 2,4-pentanedione followed by 5.0 g of benzyl chloride. The solution was stirred over night at room temperature. 200ml of 1 molar hydrochloric acid was added and the solution was extracted with dichloromethane. The extract was washed 3 times with water and the solvent was evaporated in vacuo. The residue was distilled. Yield 2.9 g, bp 150°-154° C./15 mm. the solution was extracted with dichloromethane The extract was washed 3 times with water the solvent was evaporated in vacuo The residue was distilled

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-hydrazino-6-pyridin-2-yl-[1,3,5]triazin-2-ylamine (5.25 g, 25.6 mmol), 3-benzylpentane-2,4-dione (5.0 g, 28.4 mmol), and p-toluenesulfonic acid monohydrate (0.475 g, 2.50 mmol) in dimethylsulfoxide (50 mL) was heated to 75° C. for 20 hours. The reaction mixture was allowed to cool to room temperature, and the suspension was dissolved in methylene chloride (700 mL). The solution was washed three times with water, once with brine, dried (magnesium sulfate), and concentrated to afford a moist solid. The crude product was suspended in ethyl acetate (50 mL), heated to reflux, allowed to cool to room temperature, and filtered (repeated three times). The final product was obtained as a white solid containing 3% dimethylsulfoxide by weight: 8.63 g (90%). 1H NMR (CDCl3) δ 8.84-8.53 (m, 1H), 8.48 (d, J=7.9 Hz, 1H), 7.86-7.91 (m, 1H), 7.46-7.50 (m, 1H), 7.13-7.30 (m, 5H), 6.61 (br s, 1H), 6.40 (br s, 1H), 3.83 (s, 2H), 2.79 (s, 3H), 2.24 (s, 3H) ppm. MS (ESI) m/z 358 (M+H+). to cool to room temperature The solution was washed three times with water once with brine, dried (magnesium sulfate) concentrated to afford a moist solid heated to reflux to cool to room temperature filtered (repeated three times)

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

Procedure: To a solution of sodium ethoxide (freshly prepared from sodium hydride (0.474 g, 19.8 mmol) and anhydrous ethanol (50 mL)) was added pentane-2,4-dione (6.00 g, 60.0 mmol). The resulting mixture was heated to 50° C. while a solution of benzyl bromide (3.42 g, 20 mmol) in ethanol (20 mL) was added over 30 minutes. The reaction was then heated to reflux. After 2 hours, the mixture was concentrated, and the residue was dissolved in ethyl acetate, washed three times with water, once with brine, dried (magnesium sulfate) and concentrated to afford an oil. Flash chromatography over silica (ethyl acetate/dichloromethane) afforded 3.13 g (82%) of a colorless oil. The proton spectrum showed the product exists as equal parts of the keto and enol tautomers: 1H NMR (CDCl3) δ 16.81 (s, 0.5H), 7.13-7.32 (m, 5H), 4.00 (t, J=7.6 Hz, 0.5H), 3.65 (s, 1H), 3.14 (d, J=7.6 Hz, 0.5H), 2.06-2.13 (m, 6H) ppm. was added over 30 minutes The reaction was then heated to reflux the mixture was concentrated the residue was dissolved in ethyl acetate washed three times with water once with brine, dried (magnesium sulfate) concentrated to afford an oil