Processes for production of intermediates for 2-alkyl cephem compounds
AssigneeShionogi & Co., Ltd.
InventorsKatsuki Yokoo, Shinya Hisakawa, Kenji Yamawaki, Toshiaki Aoki, Yutaka Yokota, Masatoshi Takeo, Mikito Asai
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Abstract
The invention relates to processes for the production of intermediates for preparing 2-alkyl cephem compounds useful as antimicrobial drugs. The invention provides a process which comprises oxidating a compound of the formula (I) or a salt thereof to give a compound of the formula (II) or a salt thereof wherein each symbol is as defined in the specification.
Claims30
A process for preparing a compound of the formula (II) or a salt thereof,
- wherein,
- R5A is lower alkyl;
- Y is a leaving group;
- L is a single bond, lower alkylene or lower alkenylene;
- P1 is acyl or an amino-protecting group;
- P2 is a carboxy-protecting group;
- which comprises:
- oxidation of a compound of the formula (I) or a salt thereof,
- Wherein, each symbol is as defined above,
- to give a compound of the formula (II) or a salt thereof.
A process for preparing a compound of the formula (II) or a salt thereof,
- wherein,
- R5A is lower alkyl;
- Y is a leaving group;
- L is a single bond, lower alkylene or lower alkenylene;
- P1 is acyl or an amino-protecting group;
- P2 is a carboxy-protecting group;
- which comprises:
- reacting a compound of the formula (IV) or a salt thereof,
- wherein,
- the wavy line means that the bond is a mixture of α-configuration and β-configuration;
- the other symbols are as defined above,
- with a base to give a compound of the formula (II) or a salt thereof.
A process for preparing a compound of the formula (II) or a salt thereof,
- wherein,
- R5A is lower alkyl;
- Y is a leaving group;
- L is a single bond, lower alkylene or lower alkenylene;
- P1 is acyl or an amino-protecting group;
- P2 is a carboxy-protecting group;
- which comprises:
- oxidation of a compound of the formula (I) or a salt thereof,
- wherein, each symbol is as defined above,
- to give a compound of the formula (V) or a salt thereof,
- wherein each symbol is as defined above, and
- isomerization of a compound of the formula (V) to a compound of the formula (II) or a salt thereof.
A process for preparing a compound of the formula (XVI) or a salt thereof,
- wherein,
- R5 is hydrogen or lower alkyl;
- the other symbols are as defined above,
- the wavy line means that the bond is in cis or trans configuration, or a mixture thereof;
- provided that “-L-Y” is not —CH2—O—C(═O)—CH3,
- which comprises:
- reacting aldehyde, amine and a compound of the formula (XV) or a salt thereof,
- wherein, each symbol is as defined above,
- to give a compound of the formula (XVI) or a salt thereof.
A process for preparing a compound of the formula (II) or a salt thereof,
- wherein, each symbol is as defined above;
- which comprises:
- reduction of a compound of the formula (XVI) or a salt thereof,
- wherein, each symbol is as defined above,
- to give a compound of the formula (II) or a salt thereof.
A process for preparing a compound of the formula (III) or a salt thereof,
- wherein,
- R5A is lower alkyl;
- Y is a leaving group;
- L is a single bond, lower alkylene or lower alkenylene;
- P1 is acyl or an amino-protecting group;
- P2 is a carboxy-protecting group;
- which comprises:
- reduction of a compound of the formula (II) or a salt thereof,
- wherein each symbol is as defined above,
- to give a compound of the formula (III) or a salt thereof.
A process for preparing a compound of the formula (I-1) or a salt thereof,
- wherein,
- R5A is lower alkyl;
- Y is a leaving group;
- P1 is acyl or an amino-protecting group;
- P2 is a carboxy-protecting group;
- which comprises:
- reacting a compound of the formula (VI) or a salt thereof,
- wherein, each symbol is as defined above;
- with an acid to give a compound of the formula (I-1) or a salt thereof.
A compound of the formula or a salt thereof,
- wherein
- the wavy line means that the bond is a mixture of α-configuration and β-configuration;
- the other symbols are as defined above, excluding the following;
- 1) L is a single bond and Y is halogen;
- and
- 2) L is lower alkylene or lower alkenylene and Y is acetyl.
A compound of the formula or a salt thereof,
- wherein each symbol is as defined above, excluding the following;
- 1) L is a single bond and Y is halogen;
- and
- 2) L is lower alkylene or lower alkenylene and Y is acetyl.
A compound of the formula or a salt thereof,
- wherein each symbol is as defined above, excluding the following;
- 1) L is a single bond and Y is halogen;
- and
- 2) L is lower alkylene or lower alkenylene and Y is acetyl.
A compound of the formula or a salt thereof,
- wherein each symbol is as defined above, excluding the following;
- 1) L is a single bond and Y is halogen;
- and
- 2) L is lower alkylene or lower alkenylene and Y is acetyl.
A compound of the formula or a salt thereof,
- wherein
- L is lower alkylene or lower alkenylene;
- Y is halogen;
- R5 is hydrogen;
- the wavy line means that the bond is in cis or trans configuration, or a mixture thereof;
- the other symbols are as defined above.
A method for transforming 2-α-alkyl-cephem compound to 2-β-alkyl-cephem compound, which comprises reaction of the 2-α-methyl-cephem compound with a base.
A crystal of the following compound (XVI-2):
- or solvate thereof.
A crystal of the following compound (II-3):
- or solvate thereof.
A crystal of the following compound (III-2):
- or solvate thereof.
Dependencies are inferred from the claim text.