2-acetyl-5,5-dimethylcyclohexane-1,3-dione

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

Procedure: Glucosamine hydrochloride (50 g, 231 mmol) was suspended in anhydrous methanol (500 mL), then 2-acetyl-dimedone sodium salt (47.3 g, 231 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes, then 2-acetyl-dimedone (21.1 g, 115.9 mmol) was added. The reaction mixture was stirred under reflux for 2.5 hours and monitored by tlc. At the completion of the reaction (TLC: MeCN—H20, 10:2), the reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated and the resulting solid residue was washed on a funnel with ether (3×500 mL) and dried to give crude product (75 g, 94%). No further purification was required for the next reaction. The reaction mixture was stirred under reflux for 2.5 hours the reaction mixture was cooled to room temperature filtered The filtrate was evaporated the resulting solid residue was washed on a funnel with ether (3×500 mL) dried

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

Procedure: A mixture of 4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-2,3,6-tri-O-acetyl-β-D-glucopyranosyl amine (157 mg, 0.24 mmol) and 2-acetyldimedone (81 mg, 0.45 mmol) in MeOH (5 ml) was refluxed for 5 h. The reaction mixture was evaporated, and the residue was purified by chromatography using CHCl3/EtOAc 1:1 as the mobile phase, to give 4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-2,3,6-tri-O-acetyl-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-β-D-glucopyranosyl amine (27) (106 mg, 54%). was refluxed for 5 h The reaction mixture was evaporated the residue was purified by chromatography

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

Procedure: A mixture of 4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-2,3,6-tri-O-acetyl-β-D-glucopyranosyl amine (157 mg, 0.24 mmol) and 2-acetyldimedone (81 mg, 0.45 mmol) in MeOH (5 ml) was refluxed for 5 h. The reaction mixture was evaporated, and the residue was purified by chromatography using CHCl3/EtOAc 1:1 as the mobile phase, to give 4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-2,3,6-tri-O-acetyl-N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl]-β-D-glucopyranosyl amine (27) (106 mg, 54%). was refluxed for 5 h The reaction mixture was evaporated the residue was purified by chromatography

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

Procedure: 3′-Deoxy-3′-azido-thymidine (200 mg, 0.75 mmol) was dissolved in MeOH (25 ml) and Pd/C (40 mg) was added. The suspension was stirred over a constant stream of H2 overnight. The reaction mixture was filtered, and the filtrate was concentrated. The residue was taken up in abs. EtOH (5 ml), N,N-diisopropylethylamine (0.1 ml) and 2-acetyldimedone (204 mg, 1.12 mmol) were added and the solution was refluxed for 5 h. The reaction mixture was cooled to room temperature and the product was precipitated by adding ether (50 ml) giving 3′-deoxy-3′-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-ethylamino]-thymidine (24) (200 mg, 66%). The reaction mixture was filtered the filtrate was concentrated the solution was refluxed for 5 h the product was precipitated by adding ether (50 ml)

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

Procedure: A mixture of 2-Acetamido-2-deoxy-3,4,6-tri-O-acetyl-β-D-glucopyranosyl amine (80 mg, 0.23 mmol) and 2-acetyldimedone (55 mg, 0.30 mmol) in MeOH (5 ml) was refluxed for 5 h. The reaction mixture was evaporated, the residue was purified by chromatography using CHCl3/MeOH 10:0.5 as the mobile phase, to give 2-Acetamido-3,4,6-tri-O-acetyl-1,2-dideoxy-1-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-β-D-glucopyranose (19) (70 mg, 60%). was refluxed for 5 h The reaction mixture was evaporated the residue was purified by chromatography

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

Procedure: A solution of Benzyl 2-Acetamido-2-deoxy-α-D-glucopyranoside (4.70 g, 15.11 mmol) in 1 M NaOH solution was refluxed at 120° C. for 15 h. The reaction mixture was cooled to room temperature, neutralised with 1 M HCl solution and concentrated. The residue was dissolved in dry ETOH (50 ml) and filtered. 2-Acetyldimedone (4.11 g, 22.6 mmol) and N,N-diisopropylethylamine (2 ml) were added to the filtrate, and the mixture was refluxed for 2 h. The reaction mixture was evaporated to dryness, and the residue was taken up in EtOAc (50 ml), washed with 1M KHSO4 solution, brine, and evaporated to give Benzyl 2-Deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-α-D-glucopyranoside (7) (3.78 g, 58%). concentrated The residue was dissolved in dry ETOH (50 ml) filtered the mixture was refluxed for 2 h The reaction mixture was evaporated to dryness washed with 1M KHSO4 solution, brine evaporated

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

Procedure: A solution of Benzyl 2-Acetamido-2-deoxy-α-D-glucopyranoside (4.70 g, 15.11 mmol) in 1 M NaOH solution was refluxed at 120° C. for 15 h. The reaction mixture was cooled to room temperature, neutralised with 1 M HCl solution and concentrated. The residue was dissolved in dry ETOH (50 ml) and filtered. 2-Acetyldimedone (4.11 g, 22.6 mmol) and N,N-diisopropylethylamine (2 ml) were added to the filtrate, and the mixture was refluxed for 2 h. The reaction mixture was evaporated to dryness, and the residue was taken up in EtOAc (50 ml), washed with 1M KHSO4 solution, brine, and evaporated to give Benzyl 2-Deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-α-D-glucopyranoside (7) (3.78 g, 58%). concentrated The residue was dissolved in dry ETOH (50 ml) filtered the mixture was refluxed for 2 h The reaction mixture was evaporated to dryness washed with 1M KHSO4 solution, brine evaporated

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

Procedure: Glucosamine hydrochloride (50 g, 231 mmol) was suspended in anhydrous methanol (500 mL), then 2-acetyl-dimedone sodium salt (47.3 g, 231 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes, then 2-acetyl-dimedone (21.1 g, 115.9 mmol) was added. The reaction mixture was stirred under reflux for 2.5 hours and monitored by tlc. At the completion of the reaction (TLC: MeCN—H20, 10:2), the reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated and the resulting solid residue was washed on a funnel with ether (3×500 mL) and dried to give crude product (75 g, 94%). No further purification was required for the next reaction. The reaction mixture was stirred under reflux for 2.5 hours the reaction mixture was cooled to room temperature filtered The filtrate was evaporated the resulting solid residue was washed on a funnel with ether (3×500 mL) dried

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

Procedure: Glucosamine hydrochloride (50 g, 231 mmol) was suspended in anhydrous methanol (500 mL), then 2-acetyl-dimedone sodium salt (47.3 g, 231 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes, then 2-acetyl-dimedone (21.1 g, 115.9 mmol) was added. The reaction mixture was stirred under reflux for 2.5 hours and monitored by tlc. At the completion of the reaction (TLC: MeCN—H20, 10:2), the reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated and the resulting solid residue was washed on a funnel with ether (3×500 mL) and dried to give crude product (75 g, 94%). No further purification was required for the next reaction. The reaction mixture was stirred under reflux for 2.5 hours the reaction mixture was cooled to room temperature filtered The filtrate was evaporated the resulting solid residue was washed on a funnel with ether (3×500 mL) dried

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

Procedure: A suspension of 4-Bromo-6-hydrazino-isoquinolin-1-ylamine (0.097 g, 0.38 mmol) and 2-acetyl-5,5-dimethyl-1,3-cyclohexanedione (0.074 g, 0.41 mmol) in EtOH/Acetic acid (3:1, 7 mL) is microwaved at 150° C. for 20 min. The solvent is evaporated and the residue is dried under vacuum. Purification of the crude material using a Biotage column (0-10% MeOH/CH2Cl2) afforded 0.1223 g (80%) of 1-(1-Amino-4-bromo-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indazol-4-one. LC/MS m/z=400 [M+H]+. is microwaved at 150° C. for 20 min The solvent is evaporated the residue is dried under vacuum Purification of the crude material

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

Procedure: A mixture of 2-acetyl-5,5-dimethyl-cyclohexane-1,3-dione (2 g, 11.04 mmol), prepared as described in example 2, and hydrazine hydrate (1.66 ml, 33.13 mmol) in ethanol (25 ml) was stirred at room temperature for about 3 hours and then the solvent was evaporated. The residue was dissolved in dichloromethane, washed with water and brine, dried over sodium sulfate and evaporated. The title compound was obtained after chromatography on silica gel (dichloromethane:methanol=95:5) as a colourless solid (0.8 g, 45%): m.p. 103-104° C. prepared the solvent was evaporated The residue was dissolved in dichloromethane washed with water and brine dried over sodium sulfate evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-acetyl-5,5-dimethyl-cyclohexane-1,3-dione (0.5 g, 2.75 mmol), prepared as described in example 2, and 2-hydrazino-pyridine (0.3 g, 2.75 mmol) in ethanol (15 ml) was stirred at 80° C. for 4 hours. After evaporation of the solvent, the residue was chromatographed on silica gel (cyclohexane:ethyl acetate=10:20). The title compound was obtained as a colourless solid (0.5 g, 73%): m.p. 122-123° C. prepared After evaporation of the solvent the residue was chromatographed on silica gel (cyclohexane:ethyl acetate=10:20)