Process for the preparation of substituted pyridone carboxylic acids
AssigneeGe Healthcare Limited
InventorsVIJAYA RAJ KUNIYIL KULANGARA, TILAK T. RAJ
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Abstract
The present invention relates to methods for the preparation of pyridone carboxylic acids for use as intermediates in the preparation of various synthetic organic compounds. The pyridone carboxylic acids can for example be used as intermediates in the production of potent antitumor agents, antifungal agents, antiviral agents, psychotherapeutic agents or contrast imaging agents for MRI.
Claims17
Process for the preparation of pyridone carboxylic acids of formula (I)
- wherein
- one R2 denotes H and one R2 denotes COOH;
- one R3 denotes H and one R3 denotes —ORP wherein RP denotes a protecting group and;
- R1 denotes alkyl, alkoxyalkyl, benzyloxyalkyl, di(benzyloxy)alkyl, tri(benzyloxy)alkyl or tetra(benzyloxy)alkyl
- comprising the steps of:
- a) reacting a pyranone of formula (II) with an amine of formula R1NH2 wherein R1 is defined as above or R1′NH2 wherein R1′ denotes hydroxylated alkyl or hydroxylated alkoxyalkyl in alcoholic medium together with a catalyst comprising sodium hydroxide
- wherein
- one Q1 denotes H and one Q1 denotes —CH3;
- one Q2 denotes H and one Q2 denotes —ORP wherein RP is defined as above, and when applicable protecting said hydroxyl groups in R1′ with benzyl groups, to form a compound of formula (III)
- wherein Q1, Q2 and R1 are defined as above
- and;
- b) reacting the pyridone of formula (III) in a mixture of acetic acid and acetic anhydride with SeO2 to form a compound of formula (IV)
- wherein
- one T1 denotes H and one T1 denotes —CHO;
- one T2 denotes H and one T2 denotes —ORP wherein RP is defined as above
- and;
- c) reacting the pyridone aldehyde of formula (IV) with alkalimetal peroxomonosulfate to form the compound of formula (I).
Process for the preparation of pyridones of formula (III)
- wherein
- R1 denotes alkyl, alkoxyalkyl, benzyloxyalkyl, di(benzyloxy)alkyl, tri(benzyloxy)alkyl or tetra(benzyloxy)alkyl;
- one Q1 denotes H and one Q1 denotes —CH3;
- and
- one Q2 denotes H and one Q2 denotes —ORP wherein RP is a protecting group
- by reacting a pyranone of formula (II)
- wherein Q1 and Q2 are defined as above
- with an amine of formula R1NH2 wherein R1 is defined as above or R1′NH2 wherein R1′ denotes hydroxylated alkyl or hydroxylated alkoxyalkyl in alcoholic medium together with a catalyst comprising sodium hydroxide.
Process for the preparation of pyridone aldehydes of formula (IV)
- wherein
- R1 denotes alkyl, alkoxyalkyl, benzyloxyalkyl, di(benzyloxy)alkyl, tri(benzyloxy)alkyl or tetra(benzyloxy)alkyl;
- one T1 denotes H and one T1 denotes —CHO;
- and
- one T2 denotes H and one T2 denotes —ORP wherein RP is a protecting group.
- by reacting the pyridone of formula (III)
- wherein
- one Q1 denotes H and one Q1 denotes —CH3;
- one Q2 denotes H and one Q2 denotes —ORP wherein RP is defined as above;
- and
- R1 is defined as above
- in a mixture of acetic acid and acetic anhydride with SeO2.
Process for the preparation of pyridone carboxylic acids of formula (I)
- wherein
- one R2 denotes H and one R2 denotes COOH;
- one R3 denotes H and one R3 denotes —ORP wherein RP denotes a protecting group;
- and
- R1 denotes alkyl, alkoxyalkyl, benzyloxyalkyl, di(benzyloxy)alkyl, tri(benzyloxy)alkyl or tetra(benzyloxy)alkyl
- by reacting the pyridone aldehyde of formula (IV)
- wherein
- one T1 denotes H and one T1 denotes —CHO;
- one T2 denotes H and one T2 denotes —ORP wherein RP is defined as above;
- and
- R1 is defined as above
- with alkalimetal peroxomonosulfate.
Dependencies are inferred from the claim text.