carbononitridic iodide

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

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

Procedure: Commercial ampholytes were obtained from Bio-Rad (Biolytes, pH 3-10), ICN (Iso-Lytes, pH 3-10), Geltech (Technolytes, pH 3.5-9.5) and LKB (Ampholines, pH 3.5-9.5). Ampholytes 1-8, 1A, 2A and 2B as shown in FIGS. 3, 4, and 6 were obtained from ATI. TETA, TEPA, and PEHA ampholytes were synthesized as described by Binion and Rodkey in Electrophoresis 3, 284 (1982) using a 2:1 ratio of available polyamine nitrogen to acrylic acid. A group of ampholytes termed "UT WIDE" ampholytes were prepared by mixing ampholytes made with TEPA and PEHA monomers. were prepared by mixing ampholytes

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

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

Procedure: A] treating a compound of formula (V) with a cyanogen halide which may be selected from cyanogen fluoride, cyanogen chloride, cyanogen bromide or cyanogen iodide to obtain methyl 5-acetamido-4-cyanamido-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate (VIII); B] deacetylating the intermediate (VIII) to obtain methyl 5-acetamido-4-cyanamido-6-(1,2,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate (IX). The reaction may be carried out in the presence of a deacetylating agent which may be selected from the group consisting of methanol/iodine, methanol/water, sodium t-butoxide, potassium carbonate, sodium hydroxide, or sodium methoxide; C] hydrolyzing the compound (IX) in a basic medium to obtain 5-acetamido-4-cyanamido-6-(1,2,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid of formula (VII). The base used in the reaction may be organic or inorganic. The organic base may be selected from the group consisting of pyridine, dimethylamine, trimethylamine and sodium ethoxide. The inorganic base may be selected from the group consisting of sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, sodium bicarbonate and potassium bicarbonate; and D] reacting the compound (VII) with ammonium formate in the presence of ammonia which may be in the form of gaseous ammonia, liquid ammonia or aqueous ammonia and at a high temperature, for example ranging from 80° C. to 100° C., to obtain zanamivir (I).

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methyl-6,7-dihydro-8H-indeno[5,4-d][1,3]oxazol-8-one (1.87 g, 10.0 mmol), acetone (3.68 mL, 50.0 mmol) and ICN Alumina B (manufactured by ICN, Akt.1, 20 g) were suspended in tetrahydrofuran (50 mL), and the mixture was stirred at 50° C. for 9 hr. Acetone (3.68 mL, 50.0 mmol) was added, and the mixture was further stirred for 12 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (742 mg, yield 33%). the mixture was further stirred for 12 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50)

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

Procedure: Commercial ampholytes were obtained from Bio-Rad (Biolytes, pH 3-10), ICN (Iso-Lytes, pH 3-10), Geltech (Technolytes, pH 3.5-9.5) and LKB (Ampholines, pH 3.5-9.5). Ampholytes 1-1A, 2A and 2B as shown in FIGS. 3, 4, and 6 were obtained from ATI. TETA, TEPA, and PEHA ampholytes were synthesized as described by Binion and Rodkey in Electrophoresis 3, 284 (1982) using a 2:1 ratio of available polyamine nitrogen to acrylic acid. A group of ampholytes termed "UT WIDE" ampholytes were prepared by mixing ampholytes made with TEPA and PEHA monomers. were prepared by mixing ampholytes

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

Procedure: Commercial ampholytes were obtained from Bio-Rad (Biolytes, pH 3-10), ICN (Iso-Lytes, pH 3-10), Geltech (Technolytes, pH 3.5-9.5) and LKB (Ampholines, pH 3.5-9.5). Ampholytes 1-1A, 2A and 2B as shown in FIGS. 3, 4, and 6 were obtained from ATI. TETA, TEPA, and PEHA ampholytes were synthesized as described by Binion and Rodkey in Electrophoresis 3, 284 (1982) using a 2:1 ratio of available polyamine nitrogen to acrylic acid. A group of ampholytes termed "UT WIDE" ampholytes were prepared by mixing ampholytes made with TEPA and PEHA monomers. were prepared by mixing ampholytes

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

Procedure: 1,2,6,7-Tetrahydro-8H-cyclopenta[d]furo[2,3-b]pyridin-8-one (610 mg, 3.48 mmol), acetone (1.28 mL, 17.4 mmol) and ICN Alumina B (manufactured by ICN, Akt. 1, 10 g) were suspended in tetrahydrofuran (15 mL), and the suspension was stirred at room temperature for 3 hr. Acetone (1.28 mL, 17.4 mmol) was added, and the mixture was further stirred for 3 hr. The reaction solution was filtered, and the filtrate was evaporated under reduced pressure to give the title compound (539 mg, yield 72%). the mixture was further stirred for 3 hr The reaction solution was filtered the filtrate was evaporated under reduced pressure