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

HRID 882329

반응식

HRID 882329 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

실험 절차

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).

출처 및 근거

ORD 기록
ord-d3f93a4011864d0699a3bea5741b309e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993789B2

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