Epoxycarboxamide compound, azide compound, and amino alcohol compound, and process for preparing alpha-keto amide compound using them

An amino alcohol compound represented by the formula (IX):

• 98
• wherein R1 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group or a substituted or unsubstituted arylthio group;
• R2 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R3 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, R6—O— or R7—N(R8)—, where R6 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, R7 and R8 may be the same or different from each other, and each represents a hydrogen atom, a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R4 and R5 represent the same groups as R7 and R8, respectively, and R4 and R5 optionally form a ring together with the carbon atom through which R4 and R5 are bonded;
• and X represents —O— or —N(R9)—, where R9 represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R4 or R5.

A process for preparing an α-ketoamide compound represented by the formula (X):

• 104
• wherein R1 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group or a substituted or unsubstituted arylthio group;
• R2 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R3 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, R6—O— or R7—N(R8)—, where R6 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, R7 and R8 may be the same or different from each other, and each represents a hydrogen atom, a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R4 and R5 represent the same groups as R7 and R8, respectively, and R4 and R5 optionally form a ring together with the carbon atom through which R4 and R5 are bonded;
• and X represents —O— or —N(R9)—, where R9 represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and x optionally forms a ring together with R4 or R5.
• which comprises oxidizing an amino alcohol compound represented by the formula (IX):
• 105
• wherein R1 to R5 and X have the same meanings as defined above.

A process for preparing an α-ketoamide compound represented by the formula (X):

• 106
• wherein R1 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group or a substituted or unsubstituted arylthio group;
• R2 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclicalkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R3 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, R6—O— or R7—N(R8)—, where R6 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, R7 and R8 may be the same or different from each other, and each represents a hydrogen atom, a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R4 and R5 represent the same groups as R7 and R8, respectively, and R4 and R5 optionally form a ring together with the carbon atom through which R4 and R5 are bonded;
• and X represents —O— or —N(R9)—, where R9 represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R4 or R5.
• which comprises reducing an azide compound represented by the following formula (VI):
• 107
• wherein R1 and R2 have the same meanings as defined above, to obtain an amine compound represented by the following formula (VII):
• 108
• wherein R1 and R2 have the same meanings as defined above, condensing the obtained amine compound with a carboxylic acid compound represented by the following formula (VIII):
• 109
• wherein R3 to R5 and X have the same meanings as defined above,
• to obtain an amino alcohol compound represented by the following formula (IX):
• 110
• wherein R1 to R5 and X have the same meanings as defined above,
• and then oxidizing the obtained amino alcohol compound.

A process for preparing an α-keto amide compound represented by the formula (X):

• 111
• wherein R1 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group or a substituted or unsubstituted arylthio group;
• R2 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R3 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, R6—O— or R7—N(R8)—, where R6 represents a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, R7 and R8 may be the same or different from each other, and each represents a hydrogen atom, a substituted or unsubstituted, straight, branched or cyclic alkyl group, a substituted or unsubstituted, straight, branched or cyclic alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, where the substituent for the alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group is a hydroxy group, an oxo group, a halogen atom, a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted heterocyclic group, a nitro group, a substituted or unsubstituted amino group, a substituted or unsubstituted sulfonyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted carbamoyl group, a substituted sulfonamide group, a substituted amide group, a mercapto group, a cyano group or a methylenedioxy group;
• R4 and R5 represent the same groups as R7 and R8, respectively, and R4 and R5 optionally form a ring together with the carbon atom through which R4 and R5 are bonded;
• and X represents —O— or —N(R9)—, where R9 represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R4 or R5.
• which comprises subjecting an epoxycarboxamide compound represented by the following formula (I):
• 112
• wherein R1 and R2 have the same meanings as defined above, to epoxy group ring-opening in the presence of a ring-opening agent to obtain an azide compound represented by the following formula (VI):
• 113
• wherein R1 and R2 have the same meanings as defined above;
• then reducing the obtained azide compound to obtain an amine compound represented by the following formula (VII):
• 114
• wherein R1 and R2 have the same meanings as defined above;
• condensing the obtained amine compound with a carboxylic acid compound represented by the following formula (VIII):
• 115
• wherein R3 to R5 and X have the same meanings as defined above,
• to obtain an amino alcohol compound represented by the following formula (IX):
• 116
• wherein R1 to R5 and X have the same meanings as defined above;
• and then oxidizing the obtained amino alcohol compound.