Substituted pyrazino[2,3-d]isooxazoles as intermediates for the synthesis of substituted pyrazinecarbonitriles and substituted pyrazinecarboxamides
The object of the present invention is to provide a compound which is useful as a production intermediate of pyrazine carboxamide derivative such as 6-fluoro-3-hydroxy-2-pyrazine carboxamide. The present invention provides a pyrazino[2,3-d]isoxazole derivative represented by the formula (I): wherein X represents a halogen atom, a hydroxyl group or a sulfamoyloxy group, and Y represents —C(═O)R or —CN; wherein R represents a hydrogen atom, an alkoxy group an aryloxy group, an alkyl group, an aryl group or an amino group.
1. A method for producing a compound represented by the following formula (III):
wherein X has the same meanings as those described below,
which comprises treating with a base a compound represented by the following formula (I):
wherein X represents a halogen atom, a hydroxy group or a sulfamoyloxy group, wherein a nitrogen atom of the sulfamoyloxy group may be substituted with a hydroxy group, an amino group, an alkyl group, an aryl group, a heterocyclic group, or an alkylene group with or without the mediation of a heteroatom, and said substituent may further have one or more substituents which are selected from substituent group A; and Y represents —C(═O)R or —CN; wherein R represents a hydrogen atom, an alkoxy group, an aryloxy group, an alkyl group, an aryl group or an amino group; wherein the alkoxy group, aryloxy group, alkyl group, and aryl group may be optionally substituted with one or more substituents selected from substituent group A, and the amino group may be optionally substituted with a substituent which is selected from a hydroxy group, an amino group, an alkyl group, an aryl group, a heterocyclic group or an alkylene group with or without the mediation of a heteroatom, and said substituent may further have one or more substituents which are selected from substituent group A;
substituent group A: an alkyl group containing 1 to 10 carbon atoms, an alkenyl group containing 2 to 10 carbon atoms, an alkynyl group containing 2 to 10 carbon atoms, an alkoxy group containing 1 to 10 carbon atoms, an aryloxy group containing 6 to 10 carbon atoms, a halogen atom, an aryl group containing 6 to 10 carbon atoms, a hydroxy group, an amino group, an acylamino group containing 1 to 10 carbon atoms, an alkylsulfonylamino group containing 1 to 10 carbon atoms, a carbamoyl group containing 1 to 10 carbon atoms, a sulfamoyl group containing 0 to 10 carbon atoms, a carboxy group, an alkoxycarbonyl group containing 2 to 10 carbon atoms, an acyloxy group containing 2 to 12 carbon atoms, a heterocyclic group, a cyano group, and a nitro group.
2. The method according to claim 1 , wherein X represents a fluorine atom and Y represents —C(═O)R, where R represents an alkoxy group which may be optionally substituted with one or more substituents selected from the substituent group A.
3. The method according to claim 1 , wherein X represents a fluorine atom and Y represents —C(═O)R, where R represents a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, or a n-butoxy group.
4. A method for producing a compound represented by the following formula (IV):
wherein X has the same meanings as those described below,
which comprises
a step of treating with a base a compound represented by the following formula (I):
wherein X represents a halogen atom, a hydroxy group or a sulfamoyloxy group, wherein a nitrogen atom of the sulfamoyloxy group may be substituted with a hydroxy group, an amino group, an alkyl group, an aryl group, a heterocyclic group, or an alkylene group with or without the mediation of a heteroatom, and said substituent may further have one or more substituents which are selected from substituent group A; and Y represents —C(═O)R or —CN; wherein R represents a hydrogen atom, an alkoxy group, an aryloxy group, an alkyl group, an aryl group or an amino group; wherein the alkoxy group, aryloxy group, alkyl group, and aryl group may be optionally substituted with one or more substituents selected from substituent group A, and the amino group may be optionally substituted with a substituent which is selected from a hydroxy group, an amino group, an alkyl group, an aryl group, a heterocyclic group or an alkylene group with or without the mediation of a heteroatom, and said substituent may further have one or more substituents which are selected from substituent group A;
substituent group A: an alkyl group containing 1 to 10 carbon atoms, an alkenyl group containing 2 to 10 carbon atoms, an alkynyl group containing 2 to 10 carbon atoms, an alkoxy group containing 1 to 10 carbon atoms, an aryloxy group containing 6 to 10 carbon atoms, a halogen atom, an aryl group containing 6 to 10 carbon atoms, a hydroxy group, an amino group, an acylamino group containing 1 to 10 carbon atoms, an alkylsulfonylamino group containing 1 to 10 carbon atoms, a carbamoyl group containing 1 to 10 carbon atoms, a sulfamoyl group containing 0 to 10 carbon atoms, a carboxy group, an alkoxycarbonyl group containing 2 to 10 carbon atoms, an acyloxy group containing 2 to 12 carbon atoms, a heterocyclic group, a cyano group, and a nitro group;
so as to produce a compound represented by the following formula (III):
wherein X has the same meanings as described above, and
a step of adding water to the compound represented by the formula (III).
5. The method according to claim 4 , wherein X represents a fluorine atom and Y represents —C(═O)R, where R represents an alkoxy group which may be optionally substituted with one or more substituents selected from the substituent group A.
6. The method according to claim 4 , wherein X represents a fluorine atom and Y represents —C(═O)R, where R represents a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, or a n-butoxy group.