Method for producing quinolone carboxylic acid derivative

A method for producing a compound represented by formula (1):

• [wherein
• R1 represents an optionally substituted C1 to C6 alkyl group, an optionally substituted C3 to C6 cycloalkyl group, an optionally substituted phenyl group, or an optionally substituted heteroaryl group;
• R2 represents an optionally substituted amino group, a hydrogen atom, a hydroxyl group, a thiol group, a halogenomethyl group, a C1 to C6 alkyl group, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, or a C1 to C6 alkoxy group;
• each of R3 and R4 independently represents a C3 to C6 cycloalkyl group, a hydrogen atom, a halogen atom, a phenyl group, a C1 to C6 alkyl group, a C1 to C6 alkoxy group, a C2 to C6 alkenyl group, or a C2 to C6 alkynyl group, wherein the cycloalkyl group may have an amino group as a substituent;
• each of the alkyl group, alkoxy group, alkenyl group, and alkynyl group may be linear or branched;
• and the alkyl group may have one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a halogen atom, a CL to C6 alkylthio group, a C1 to C6 alkoxy group, a C3 to C6 cycloalkyl group, a C1 to C6 alkylamino group, a C3 to C6 cycloalkylamino group, a phenyl group which may be substituted by a C1 to C6 alkoxy group or a halogen atom, a furyl group which may be substituted by a C1 to C6 alkoxy group or a halogen atom, and a thiazolyl group which may be substituted by a C1 to C6 alkoxy group or a halogen atom, or R3 and R4 may be linked together to form
• (a) a spiro-ring structure of a 3- to 6-membered ring structure including the carbon atom to which R3 and R4 are bonded, wherein the spiro ring may have a nitrogen atom, an oxygen atom, or a sulfur atom, as a ring-member atom;
• the formed ring may be substituted by a halogen atom, a C1 to C6 alkyl group, or an amino group;
• and the alkyl group may have a group selected from the group consisting of a halogen atom, a C1 to C6 alkyl group, and a C1 to C6 alkoxy group, as a substituent, or
• (b) an exo-methylene group bonded via a double bond, wherein the exo-methylene group may have one or two substituents selected from the group consisting of a hydroxyl group, an amino group, a halogen atom, a C1 to C6 alkylthio group, and a C1 to C6 alkoxy group;
• “A” represents a nitrogen atom or a partial structure represented by the following formula:
• (wherein X2 represents a hydrogen atom, a hydroxyl group, a cyano group, a halogen atom, a C1 to C6 alkyl group, a C1 to C6 alkoxy group, a halogenomethyl group, or a halogenomethoxy group, wherein X2 and R1 may be integrated with a part of the skeleton, to form a ring, and the formed ring may have a C1 to C6 alkyl group as a substituent);
• W represents —CHR5—, —O—, or —NR6— (wherein R5 represents a hydrogen atom, a halogen atom, a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, or a C1 to C6 alkoxy group;
• the cycloalkyl group may have an amino group as a substituent;
• the alkyl group may have one or more substituents selected from the group consisting of a hydroxyl group, an amino group, a halogen atom, a C1 to C6 alkylthio group, and a C1 to C6 alkoxy group;
• R5 and R3 or R4 may together form a C3 to C6 cycloalkane or a 5- to 7-membered saturated heterocycle with a carbon atom to which these Rs are bonded;
• and the formed cycloalkane or saturated heterocycle may have a C1 to C6 alkyl group or an amino group as a substituent, and R6 represents a hydrogen atom, a C1 to C6 alkyl group, or a C3 to C6 cycloalkyl group);
• X1 represents a hydrogen atom or a halogen atom;
• Y represents a hydrogen atom, or an amino group, a C1 to C6 alkyl, a C1 to C6 alkylamino group, a C3 to C6 cycloalkyl group, or a group which can be readily transformed by chemical means to an amino group or a C1 to C6 alkylamino group, these groups each being bonded to any carbon atom of the saturated heterocyclic ring;
• and
• n is 0 to 2], a salt thereof, or a hydrate of the compound or salt, characterized in that the method comprises
• allowing to cause a reaction in a mixture containing a compound represented by formula (2):
• (wherein X represents a halogen atom, and R1, R2, X1, and A have the same meanings as defined above), a salt of a compound represented by formula (3):
• (wherein W, Y, R3, R4, and n have the same meanings as defined above], and a boron derivative in a solvent in the presence of a base, to thereby form a boron chelate compound, and
• removing a boron chelate moiety from the boron chelate compound.