EPOXYCARBOXAMIDE COMPOUND, AZIDE COMPOUND, AND AMINO ALCOHOL COMPOUND, AND PROCESS FOR PREPARING a-KETO AMIDE COMPOUND USING THEM

Abstract

The present invention is directed to providing epoxycarboxamide compounds, azide compounds and amino alcohol compounds which serve as manufacturing intermediates that can lead to useful α-ketoamide compounds, and the present invention is also is directed to processes for preparing α-ketoamide compounds using the intermediates. The epoxycarboxamide compounds, azide compounds and amino alcohol compounds are represented by the following formulae: wherein R 1 , R 2 , R 3 , R 4 and R 5 , as well as subvariables for one or more of R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein.

1 - 14 . (canceled) 
     
     
         15 . An amino alcohol compound represented by the formula (IX): 
       
         
           
           
               
               
           
         
         wherein R 1  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; R 2  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; R 3  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, R 6 —O— or R 7 —N(R 8 )—, where R 6  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, R 7  and R 8  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; R 4  and R 5  represent the same groups as R 7  and R 8 , respectively, and R 4  and R 5  optionally form a ring together with the carbon atom through which R 4  and R 5  are bonded; and X represents —O— or —N(R 9 )—, where R 9  represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R 4  or R 5 . 
       
     
     
         16 . The amino alcohol compound according to  claim 15 , wherein the compound represented by the formula (IX) is a compound represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above. 
       
     
     
         17 . The amino alcohol compound according to  claim 15 , wherein the compound represented by the formula (IX) is a compound represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above. 
       
     
     
         18 . The amino alcohol compound according to  claim 15 , wherein the compound represented by the formula (IX) is a compound represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above. 
       
     
     
         19 . The amino alcohol compound according to  claim 15 , wherein the compound represented by the formula (IX) is a compound represented by the following formula: 
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above. 
       
     
     
         20 . The amino alcohol compound according to  claim 15 , wherein R 1  is a substituted or unsubstituted, straight, branched or cyclic alkyl group or a substituted or unsubstituted, straight, branched or cyclic alkenyl group, R 2  is a substituted or unsubstituted, straight, branched or cyclic alkyl group, R 3  is a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted heterocyclic group, R 4  and R 5  are one of which is a hydrogen atom and the another is a substituted or unsubstituted, straight, branched or cyclic alkyl group or R 4  and R 5  may form a saturated cyclic alkyl group together with the carbon atom through which they are bonded, and X is —N(R 9 )—, where R 9  represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, or may form a heterocyclic ring together with R 4  or R 5 . 
     
     
         21 . The amino alcohol compound according to  claim 15 , wherein R 4  and R 5  form a saturated cyclic alkyl group having 5 to 7 carbon atoms together with the carbon atom through which they are bonded. 
     
     
         22 . The amino alcohol compound according to  claim 21 , wherein R 4  and R 5  form a saturated cyclic alkyl group having 6 carbon atoms together with the carbon atom through which they are bonded. 
     
     
         23 . The amino alcohol compound according to  claim 15 , wherein X is —NH—. 
     
     
         24 . The amino alcohol compound according to  claim 15 , wherein R 1  is an unsubstituted alkyl group. 
     
     
         25 . The amino alcohol compound according to  claim 24 , wherein R 1  is an n-butyl group. 
     
     
         26 . The amino alcohol compound according to  claim 15 , wherein R 2  is a substituted or unsubstituted cyclic alkyl group. 
     
     
         27 . The amino alcohol compound according to  claim 26 , wherein R 2  is a substituted or unsubstituted cyclohexyl group. 
     
     
         28 . The amino alcohol compound according to  claim 26 , wherein a substituent for the alkyl group of R 2  is a hydroxy group. 
     
     
         29 . The amino alcohol compound according to  claim 28 , wherein R 2  is represented by the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         30 . The amino alcohol compound according to  claim 15 , wherein R 3  is a morpholino group. 
     
     
         31 . A process for preparing an α-ketoamide compound represented by the formula (X): 
       
         
           
           
               
               
           
         
         wherein R 1  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; R 2  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; R 3  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, R 6 —O— or R 7 —N(R 8 )—, where R 6  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, R 7  and R 8  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; R 4  and R 5  represent the same groups as R 7  and R 8 , respectively, and R 4  and R 5  optionally form a ring together with the carbon atom through which R 4  and R 5  are bonded; and X represents —O— or —N(R 9 )—, where R 9  represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R 4  or R 5 . 
       
       which comprises oxidizing an amino alcohol compound represented by the formula (IX): 
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above. 
       
     
     
         32 . A process for preparing an α-ketoamide compound represented by the formula (X): 
       
         
           
           
               
               
           
         
         wherein R 1  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; R 2  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 hetero-cyclic 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; R 3  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, R 6 —O— or R 7 —N(R 8 )—, where R 6  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, R 7  and R 8  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 alkyl-thio 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 methyl-enedioxy group; R 4  and R 5  represent the same groups as R 7  and R 8 , respectively, and R 4  and R 5  optionally form a ring together with the carbon atom through which R 4  and R 5  are bonded; and X represents —O— or 
         —N(R 9 )—, where R 9  represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R 4  or R 5 . 
       
       which comprises reducing an azide compound represented by the following formula (VI): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  have the same meanings as defined above, 
       
       to obtain an amine compound represented by the following formula (VII): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  have the same meanings as defined above, condensing the obtained amine compound with a carboxylic acid compound represented by the following formula (VIII): 
       
       
         
           
           
               
               
           
         
         wherein R 3  to R 5  and X have the same meanings as defined above, to obtain an amino alcohol compound represented by the following formula (IX): 
       
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above, and then oxidizing the obtained amino alcohol compound. 
       
     
     
         33 . A process for preparing an α-keto amide compound represented by the formula (X): 
       
         
           
           
               
               
           
         
         wherein R 1  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; R 2  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; R 3  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, R 6 —O— or R 7 —N(R 8 )—, where R 6  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, R 7  and R 8  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; R 4  and R 5  represent the same groups as R 7  and R 8 , respectively, and R 4  and R 5  optionally form a ring together with the carbon atom through which R 4  and R 5  are bonded; and X represents —O— or —N(R 9 )—, where R 9  represents a hydrogen atom or a substituted or unsubstituted, straight, branched or cyclic alkyl group, and X optionally forms a ring together with R 4  or R 5    
       
       which comprises subjecting an epoxycarboxamide compound represented by the following formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  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): 
       
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  have the same meanings as defined above; 
       
       then reducing the obtained azide compound to obtain an amine compound represented by the following formula (VII): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  have the same meanings as defined above; 
       
       condensing the obtained amine compound with a carboxylic acid compound represented by the following formula (VIII): 
       
         
           
           
               
               
           
         
         wherein R 3  to R 5  and X have the same meanings as defined above, to obtain an amino alcohol compound represented by the following formula (IX): 
       
       
         
           
           
               
               
           
         
         wherein R 1  to R 5  and X have the same meanings as defined above; 
       
       and then oxidizing the obtained amino alcohol compound. 
     
     
         34 - 36 . (canceled)