Cyanogen Bromide → methyl 5-acetamido-4-cyanamido-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate

HRID 882329

反応式

HRID 882329 の反応式
[C:1]([NH:4][CH:5]1[CH:10]([CH:11]([O:22][C:23](=[O:25])[CH3:24])[CH:12]([O:18][C:19](=[O:21])[CH3:20])[CH2:13][O:14][C:15](=[O:17])[CH3:16])[O:9][C:8]([C:26]([O:28][CH3:29])=[O:27])=[CH:7][CH:6]1[NH2:30])(=[O:3])[CH3:2].[N:31]#[C:32]F.N#CCl.N#CBr.N#CI>>[C:1]([NH:4][CH:5]1[CH:10]([CH:11]([O:22][C:23](=[O:25])[CH3:24])[CH:12]([O:18][C:19](=[O:21])[CH3:20])[CH2:13][O:14][C:15](=[O:17])[CH3:16])[O:9][C:8]([C:26]([O:28][CH3:29])=[O:27])=[CH:7][CH:6]1[NH:30][C:32]#[N:31])(=[O:3])[CH3:2]

参加物

6

反応物 5

HCID 10476Cyanogen BromideHCID 10477Cyanogen ChlorideHCID 10478Cyanogen iodideHCID 137036Cyanogen fluoride ((CN)F)HCID 67367461methyl 5-acetamido-4-amino-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate

生成物 1

HCID 75151075methyl 5-acetamido-4-cyanamido-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate

実験手順

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).

出典と根拠

ORDレコード
ord-d3f93a4011864d0699a3bea5741b309e
出典データセット
uspto-grants-2015_03
特許番号
US08993789B2

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