Intermediate halophenyl derivatives and their use in a process for preparing azole derivatives
AssigneeBasilea Pharmaceutica AG
InventorMilan Soukup
Life of this patent
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Abstract
Novel halophenyl derivatives of the general formula (I), wherein R1 is halogen, a leaving group or 1H-1,2,4-triazol-1-yl and R2 is ethynyl or carboxy, X1 is halogen and X2 and X3 are each independently hydrogen or halogen, and their manufacture are described. They are intermediates for manufacturing azole derivatives of the general formula (V) which are valuable medicaments useful for treating systemic mycoses.
Claims28
Halophenyl compounds of the formula
- wherein R1 is halogen, lower alkylsulfonyl, phenylsulfonyl, p-tolylsulfonyl or 1H-1,2,4-triazol-1-yl and R2 is ethynyl;
- X1 is halogen and X2 and X3 are each independently hydrogen or halogen.
The process for the manufacture of halophenyl compounds of the formula
- wherein R11 is halogen, lower alkylsulfonyl, phenylsulfonyl or p-tolylsulfonyl, X1 is halogen and X2 and X3 are each independently hydrogen or halogen,
- comprising reacting a halophenyl compound of the formula
- wherein R11, X1, X2 and X3 are as above,
- with an alkyne of the general formula
- wherein L is halogen lower alkylsulfonyl, phenylsulfonyl or p-tolylsulfonyl,
- in the presence of a palladium catalyst and an organometallic reagent in an apolar organic solvent.
The process of manufacturing a triazole carboxylic acid of the formula
- wherein X1is halogen, X2 and X3 are each independently hydrogen or halogen
- comprising reacting a ketone of the formula
- wherein R11 is halogen, lower alkylsulfonyl, phenylsufonyl, p-tolylsulfonyl;
- and X1, X2 and X3 are as above,
- with an alkyne of the formula
- wherein L is halogen, lower alkylsulfonyl, phenylsulfonyl, or p-tolylsulfonyl and X1, X2 and X3 are as above
- in the presence of a paladium catalyst and an organometallic reagent in an apolar organic solvent to produce a phenyl hydroxy alkyne of the formula
- wherein R11, X1, X2 and X3 are as above
- and thereafter reacting said phenyl hydroxy alkyne compound with 1,2,4-triazole to form said a hydroxy phenyl triazole of the formula I-3
- wherein X1, X2 and X3 are as above;
- and thereafter oxidizing said hydroxy phenyl triazole of the formula I-3 to form said triazole carboxylic acid of the formula I-2.
The process of producing a triazole carboxylic acid of the formula
- wherein X1is halogen and X2 and X3 are independently hydrogen or halogen;
- comprising reacting a halophenyl compound of the formula
- wherein R11 is halogen, lower alkylsulfonyl, phenylsufonyl, or p-tolylsulfonyl;
- X1, X2 and X3 are as above;
- with an alkyne of the formula
- wherein L is halogen, lower alkylsulfonyl, phenylsulfonyl, or p-tolylsulfonyl;
- in the presence of a paladium catalyst and an organometallic reagent in an apolar organic solvent to produce a phenyl hydroxy alkyne of the formula
- wherein R11, X1, X2 and X3 are as above;
- oxidizing said alkyne halo phenyl carboxylic acid to produce an alkyne phenyl carboxylic acid of the formula
- wherein R11, X1, X2 and X3 are as above;
- and
- thereafter reacting said alkyne phenyl carboxylic acid of the formula I-4 with 1,2,4-triazole to form said triazole carboxylic acid of the formula I-2.
Dependencies are inferred from the claim text.