Intermediate of 6-Substituted 1-Methyl-1-H-Benzimidazole Derivative and Method for Producing Same

A compound having the formula (III) shown below

• wherein
• R2 represents a hydrogen atom,
• a C1-C6 alkyl group which is unsubstituted or substituted with from 1 to 5 substituents from a Substituent group α,
• a C3-C6 cycloalkyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group,
• a phenyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, or
• a 5- or 6-membered heterocyclic group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, said heterocyclic group contains from 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and
• X represents an oxygen atom, a sulfur atom or a nitrogen atom, said nitrogen atom is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkylsulfonyl group and a C6-C10 arylsulfonyl group, the Substituent group α represents
• a C3-C6 cycloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C6-C10 aryl group, a carboxyl group, a formyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkyloxycarbonyl group, a C6-C10 aryloxycarbonyl group, a carbamoyl group, an N—C1-C6 alkylcarbamoyl group, an N,N-di(C1-C6 alkyl)carbamoyl group, a hydroxyl group, a C1-C6 alkoxy group, a C6-C10 aryloxy group, a C1-C6 alkylcarbonyloxy group, a C6-C10 arylcarbonyloxy group, an amino group, a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C6-C10 arylamino group, a di(C6-C10 aryl)amino group, a mercapto group, a C1-C6 alkylthio group, a C6-C10 arylthio group, a C1-C6 alkylsulfinyl group, a C6-C10 arylsulfinyl group, a C1-C6 alkylsulfonyl group, a C6-C10 arylsulfonyl group, a sulfonic acid group, a halogen atom, a nitro group, and a cyano group.

A method for the preparation of a compound having a formula (I) or a pharmaceutically acceptable salt thereof shown below, comprising reducing the nitro group of a compound having the following formula (III), followed by carrying out an intramolecular dehydration condensation

• wherein
• R2 represents a hydrogen atom,
• a C1-C6 alkyl group which is unsubstituted or substituted with from 1 to 5 substituents from a Substituent group α,
• a C3-C6 cycloalkyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group,
• a phenyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, or
• a 5- or 6-membered heterocyclic group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, said heterocyclic group contains from 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and
• X represents an oxygen atom, a sulfur atom or a nitrogen atom, said nitrogen atom is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkylsulfonyl group and a C6-C10 arylsulfonyl group,
• the Substituent group α represents
• a C3-C6 cycloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C6-C10 aryl group, a carboxyl group, a formyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkyloxycarbonyl group, a C6-C10 aryloxycarbonyl group, a carbamoyl group, an N—C1-C6 alkylcarbamoyl group, an N,N-di(C1-C6 alkyl)carbamoyl group, a hydroxyl group, a C1-C6 alkoxy group, a C6-C10 aryloxy group, a C1-C6 alkylcarbonyloxy group, a C6-C10 arylcarbonyloxy group, an amino group, a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C6-C10 arylamino group, a di(C6-C10 aryl)amino group, a mercapto group, a C1-C6 alkylthio group, a C6-C10 arylthio group, a C1-C6 alkylsulfinyl group, a C6-C10 arylsulfinyl group, a C1-C6 alkylsulfonyl group, a C6-C10 arylsulfonyl group, a sulfonic acid group, a halogen atom, a nitro group, and a cyano group,
• wherein R2 and X have the same meanings as those described above.

A method for the preparation of a compound having the following general formula (III) comprising carrying out a condensation reaction of a compound having the following formula (II) and 4-[(2,4-dioxothiazolidin-5-yl)methyl]phenoxyacetic acid

• wherein
• R2 represents a hydrogen atom,
• a C1-C6 alkyl group which is unsubstituted or substituted with from 1 to 5 substituents from a
• Substituent group α,
• a C3-C6 cycloalkyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group,
• a phenyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, or
• a 5- or 6-membered heterocyclic group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, said heterocyclic group contains from 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and
• X represents an oxygen atom, a sulfur atom or a nitrogen atom, said nitrogen atom is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkylsulfonyl group and a C6-C10 arylsulfonyl group,
• the Substituent group α represents
• a C3-C6 cycloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C6-C10 aryl group, a carboxyl group, a formyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkyloxycarbonyl group, a C6-C10 aryloxycarbonyl group, a carbamoyl group, an N—C1-C6 alkylcarbamoyl group, an N,N-di(C1-C6 alkyl)carbamoyl group, a hydroxyl group, a C1-C6 alkoxy group, a C6-C10 aryloxy group, a C1-C6 alkylcarbonyloxy group, a C6-C10 arylcarbonyloxy group, an amino group, a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C6-C10 arylamino group, a di(C6-C10 aryl)amino group, a mercapto group, a C1-C6 alkylthio group, a C6-C10 arylthio group, a C1-C6 alkylsulfinyl group, a C6-C10 arylsulfinyl group, a C1-C6 alkylsulfonyl group, a C6-C10 arylsulfonyl group, a sulfonic acid group, a halogen atom, a nitro group, and a cyano group,
• wherein R2 and X represent the same meanings as those described above.

A method for the preparation of a compound having the following formula (II) comprising preparing N-(5-chloro-2-nitrophenyl)-N-methylamine by reacting 2,4-dichloronitrobenzene with methylamine, followed by reaction reacting the resulting N-(5-chloro-2-nitrophenyl)-N-methylamine without isolation with a compound having a formula of R2—X—H in the presence of a base,

• wherein
• R2 represents a hydrogen atom,
• a C1-C6 alkyl group which is unsubstituted or substituted with from 1 to 5 substituents from a Substituent group α,
• a C3-C6 cycloalkyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group,
• a phenyl group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, or
• a 5- or 6-membered heterocyclic group which is unsubstituted or substituted with from 1 to 5 substituents selected from the group consisting of the Substituent group α, a C1-C6 alkyl group and a halomethyl group, said heterocyclic group contains from 1 to 4 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and
• X represents an oxygen atom, a sulfur atom or a nitrogen atom, said nitrogen atom is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkylcarbonyl group, a C6-C10 arylcarbonyl group, a alkylsulfonyl group and a C6-C10 arylsulfonyl group,
• the Substituent group α represents
• a C3-C6 cycloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C6-C10 aryl group, a carboxyl group, a formyl group, a alkylcarbonyl group, a C6-C10 arylcarbonyl group, a C1-C6 alkyloxycarbonyl group, a C6-C10 aryloxycarbonyl group, a carbamoyl group, an N—C1-C6 alkylcarbamoyl group, an N,N-di(C1-C6 alkyl)carbamoyl group, a hydroxyl group, a C1-C6 alkoxy group, a C6-C10 aryloxy group, a C1-C6 alkylcarbonyloxy group, a C6-C10 arylcarbonyloxy group, an amino group, a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C6-C10 arylamino group, a di(C6-C10 aryl)amino group, a mercapto group, a C1-C6 alkylthio group, a C6-C10 arylthio group, a C1-C6 alkylsulfinyl group, a C6-C10 arylsulfinyl group, a C1-C6 alkylsulfonyl group, a C6-C10 arylsulfonyl group, a sulfonic acid group, a halogen atom, a nitro group, and a cyano group,
• wherein R2 and X represent the same meanings as those described above.