Processes for producing pyrazoloacridone derivative and synthetic intermediate thereof

A process for producing a pyrazoloacridone derivative represented by formula (V):

• wherein R3a, R3b, R3c and R3d are the same or different and each represents a hydrogen atom, lower alkyl, —(CH2)n—Y1 [wherein n represents an integer of 1 to 6;
• and Y1 represents hydroxy, lower alkoxy, or —NR4aR4b {wherein R4a and R4b are the same or different and each represents a hydrogen atom, lower alkyl, or —(CH2)m—Y2 [wherein m represents an integer of 1 to 6;
• and Y2 represents hydroxy, lower alkoxy, or —NR5aR5b (wherein R5a and R5b are the same or different and each represents a hydrogen atom or lower alkyl)], or R4a and R4b forms a heterocyclic group together with the adjacent nitrogen atom}], or —CH((CH2)pOH2 (wherein p represents an integer of 1 to 5), which comprises steps of:
• reacting 2,6-difluorobenzonitrile with a compound represented by formula (II):
• wherein R1 represents a hydrogen atom —CH2X (wherein X represents a hydrogen atom, hydroxy, lower alkoxy or benzyloxy), or —OC(═O)R3 (wherein R3 represents lower alkyl);
• and R2 represents a hydrogen atom, nitro, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkylthio, or a substituted or unsubstituted aryl in the presence of a base to produce a compound represented by formula (VI):
• ;converting the resulting compound represented by formula (VI) into a compound represented by formula (III):
• wherein R represents lower alkyl;
• and
• hydrolyzing a cyano group of the resulting compound represented by formula (III) to produce a 1-(2-carboxyphenyl)indazole derivative represented by formula (IV):
• .

A process for producing a 1-(2-carboxyphenyl)indazole derivative represented by formula (IV):

• wherein R is lower alkyl, R1 represents a hydrogen atom, —CH2X (wherein X represents a hydrogen atom, hydroxy, lower alkoxy or benzyloxy), or —OC(═O)R3 (wherein R3 represents lower alkyl);
• and R2 represents a hydrogen atom, nitro, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkylthio, or a substituted or unsubstituted aryl which comprises steps of:
• reacting a compound represented by formula (I):
• in the presence of a base with a compound represented by formula (II):
• to produce a compound represented by formula (III):
• ;
• and
• hydrolyzing a cyano group of the resulting compound represented by formula (III).

A process for producing a 1-(2-carboxyphenyl)indazole derivative represented by formula (IV):

• wherein R is lower alkyl, R1 represents a hydrogen atom, —CH2X (wherein X represents a hydrogen atom, hydroxy, lower alkoxy or benzyloxy), or —OC(═O)R3 (wherein R3 represents lower alkyl);
• and R2 represents a hydrogen atom, nitro, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkylthio, or a substituted or unsubstituted aryl, which comprises:
• reacting 2,6-difluorobenzonitrile in the presence of a base with a compound represented by formula (II):
• to produce a compound represented by formula (VI):
• ;
• converting the resulting compound represented by formula (VI) into a compound represented by formula (III):
• ;
• and
• hydrolyzing a cyano group of the resulting compound represented by formula (III).

A process for producing a compound represented by formula (III):

• wherein R is lower alkyl, R1 represents a hydrogen atom, —CH2X (wherein X represents a hydrogen atom, hydroxy, lower alkoxy or benzyloxy), or —OC(═O)R3 (wherein R3 represents lower alkyl);
• and R2 represents a hydrogen atom, nitro, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkylthio, or a substituted or unsubstituted aryl, which comprises:
• reacting a compound represented by formula (I):
• in the presence of a base with a compound represented by formula (II):
• .

A process for producing a compound represented by formula (VI):

• wherein wherein R1 represents a hydrogen atom, —CH2X (wherein X represents a hydrogen atom, hydroxy, lower alkoxy or benzyloxy), or —OC(═O)R3 (wherein R3 represents lower alkyl);
• and R2 represents a hydrogen atom, nitro, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkylthio, or a substituted or unsubstituted aryl, which comprises:
• reacting 2,6-difluorobenzonitrile in the presence of a base with a compound represented by formula (II):
• .