Method for manufacturing a 6-substituted 1-methyl-1h-benzimidazole derivative and an intermediate of said method

A method for manufacturing a 6-substituted 1-methyl-1H-benzimidazole compound represented by the formula (IV) or a salt thereof, or a hydrate thereof,

• wherein R3 represents a hydrogen atom or a C1-C4 alkyl group, comprising contacting a compound represented by formula (II)
• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom,
• with an acid, and, if at least one of R1 or R2 is a protecting group for the nitrogen atom, removing said protecting group(s) to form said compound of the formula (IV).

A compound represented by the formula (II):

• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom.

A method for manufacturing a compound represented by the formula (II),

• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom, comprising reacting a compound represented by the formula (I)
• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom,
• with {4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy}acetic acid in the presence of a condensing agent to form said compound of the formula (II).

A method for manufacturing a compound represented by the formula (II),

• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom, comprising reacting a compound represented by the formula (I)
• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom,
• with an acid chloride or a mixed acid anhydride of {4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy}acetic acid to form said compound of the formula (II).

A compound represented by the formula (I) or a salt thereof:

• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom;
• and R2 represents a hydrogen atom or a protective group for the nitrogen atom.

A method for manufacturing a compound represented by the formula (I),

• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom,
• comprising hydrogenating a 5-substituted N-methyl-2-nitroaniline compound represented by the formula (III)
• wherein R1 represents a hydrogen atom, a C1-C4 alkyl group, or a protective group for the nitrogen atom, and R2 represents a hydrogen atom or a protective group for the nitrogen atom, to form said compound of the formula (I).