Method for producing benzazepinone
It is an object of the present invention to provide 2-iminocarboxylic acid derivatives, and a practically suitable industrial method for producing benzazepinones in a short process under mild conditions. The present invention provides a method for producing a benzazepinone or a salt thereof, which comprises opening a ring of an isoquinoline derivative and subsequently converting the thus generated amine into a benzazepinone through lactamization reaction.
1. A method for producing a benzazepinone represented by formula (2), or a salt thereof, which comprises:
opening a ring of an isoquinoline derivative represented by formula (1) by reaction of the isoquinoline derivative with an amine or a salt thereof; and subsequently converting the thus generated amine into a benzazepinone through a lactamization reaction by heating the amine in a solvent; wherein
formula (1) is
wherein R 1 represents an alkoxy group; each of R 2 to R 5 independently represents a hydrogen atom, an alkoxy group, or an alkyl group containing 1 to 10 carbon atoms; X represents an ethylene group or an arylene group; and Q is a tertiary or quaternary nitrogen atom, which, in those cases of a quaternary form, is substituted with an alkyl group or an aryl group containing 1 to 10 carbon atoms and has counter ion(s) Y − , wherein Y − represents a halide ion, an inorganic acid ion, an alkylsulfate ion, a mesylate ion, a tosylate ion, an alkylsulfonate ion, an organic acid ion, and/or a hydroxide ion;
and formula (2) is
wherein R 2 to R 5 and X have the same definitions as described above; R 6 represents a hydrogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, or an alkyl group or an aryl group containing 1 to 10 carbon atoms; and R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms.
2. A method for producing an aminobenzazepinone or a salt thereof, which comprises:
producing a benzazepinone represented by the formula (2) or a salt thereof through the method according to claim 1 ; and
reducing the benzazepinone represented by (2) or the salt thereof which has been produced in the above manner, to thereby convert into an aminobenzazepinone represented by formula (4); wherein
formula (2) is
wherein each of R 2 to R 5 independently represents a hydrogen atom, an alkoxy group, or an alkyl group containing 1 to 10 carbon atoms; R 6 represents a hydrogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, or an alkyl group or an aryl group containing 1 to 10 carbon atoms; R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms; and X represents an ethylene group or an arylene group,
and formula (4) is
wherein R 2 to R 5 , R 7 , and X have the same definitions as described above.
3. The method according to claim 2 , which further comprises resolving the aminobenzazepinone into an optically active aminobenzazepinone.
4. A method for producing a 2-iminocarboxylic acid derivative represented by formula (3) or a salt thereof, which comprises reacting an isoquinoline derivative represented by formula (1) with an amine or a salt thereof; wherein
formula (1) is
wherein R 1 represents an alkoxy group; each of R 2 to R 5 independently represents a hydrogen atom, an alkoxy group, or an alkyl group containing 1 to 10 carbon atoms; X represents an ethylene group or an arylene group; and Q is a tertiary or quaternary nitrogen atom, which, in those cases of a quaternary form, is substituted with an alkyl group or an aryl group containing 1 to 10 carbon atoms and has counter ion(s) Y − , wherein Y − represents a halide ion, an inorganic acid ion, an alkylsulfate ion, a mesylate ion, a tosylate ion, an alkylsulfonate ion, an organic acid ion, and/or a hydroxide ion; and
formula (3) is
wherein R 1 to R 5 and X have the same definitions as described above for formula (1); R 6 represents a hydrogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, or an alkyl group or an aryl group containing 1 to 10 carbon atoms; and R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms.
5. A method for producing a benzazepinone represented by formula (2) or a salt thereof, which comprises lactamizing a 2-iminocarboxylic acid derivative represented by formula (3) or a salt thereof; wherein
formula (3) is
wherein R 1 represents an alkoxy group; each of R 2 to R 5 independently represents a hydrogen atom, an alkoxy group, or an alkyl group containing 1 to 10 carbon atoms; R 6 represents a hydrogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, or an alkyl group or an aryl group containing 1 to 10 carbon atoms; R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms; and X represents an ethylene group or an arylene group; and
formula (2) is
wherein R 2 to R 7 and X have the same definitions as described above.
6. A 2-iminocarboxylic acid derivative represented by formula (3) or a salt thereof
wherein R 1 represents an alkoxy group; each of R 2 to R 5 independently represents a hydrogen atom, an alkoxy group, or an alkyl group containing 1 to 10 carbon atoms; R 6 represents a hydrogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, or an alkyl group or an aryl group containing 1 to 10 carbon atoms; R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms; and X represents an ethylene group or an arylene group.
7. A 3,4-dihydroisoquinolinium salt represented by formula (1a):
wherein R 1 represents an alkoxy group; R 7 represents a hydrogen atom or an alkyl group containing 1 to 10 carbon atoms; and Y − represents a halide ion, an inorganic acid ion, an alkylsulfate ion, a mesylate ion, a tosylate ion, an alkylsulfonate ion, an organic acid ion, and/or a hydroxide ion.