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US 2009/0264648 A1Published application
Synthesis of pyrazoles
AssigneesWyeth, Siena Biotech S.P.A.
InventorsWarren Chew, Zheng Wang, Gloria Cheal, Martial Bertrand, John Potoski, Mahmoud Mirmehrabi, Arianna Nencini, Riccardo Zanaletti
Life of this patent
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Abstract
The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
Claims34
A method comprising the steps of:
- providing a compound of formula I-1:
- wherein:
- Ring A is a 4-8 membered saturated ring, having 0-2 heteroatoms independently selected from O, N, or S in addition to the nitrogen depicted in Ring A, wherein Ring A is independently substituted with 0-4 R′ groups;
- R′ is selected from the group consisting of mono- or di-[linear, branched or cyclic C1-6 alkyl]aminocarbonyl;
- linear, branched or cyclic C1-6 alkyl, alkoxy, or acyl;
- Y and Y′ are each independently N or C, with the proviso that at least one of Y or Y′ is N;
- T is a C3-5 bivalent hydrocarbon chain, optionally carrying an oxo group and optionally substituted with one or more halogen, hydroxy, C1-5 alkyl, alkoxy, fluoroalkyl, hydroxyalkyl, alkylidene, or fluoroalkylidene groups;
- C3-6 cycloalkane-1,1-diyl, oxacycloalkane-1,1-diyl, C3-6 cycloalkane-1,2-diyl, or oxacycloalkane-1,2-diyl groups, wherein the bonds of the 1,2-diyl radical form a fused ring with the T chain;
- and with the proviso that when T carries an oxo group, said oxo group is not part of an amide bond;
- and
- Ar is a group selected from 6-10 membered aryl, or 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;
- wherein Ar is optionally substituted with one or more substituents independently selected from halogen;
- hydroxy;
- mercapto;
- cyano;
- nitro;
- amino;
- sulfonyl;
- linear, branched or cyclic (C1-C6) alkyl, trihaloalkyl, di- or trihaloalkoxy, alkoxy, or alkylcarbonyl;
- (C3-C6) cycloalkyl-(C1-C6) alkoxy;
- (C3-C6) cycloalkyl-(C1-C6) alkyl;
- linear, branched, or cyclic (C1-C6) alkylcarbonylamino;
- mono- or di-, linear, branched, or cyclic (C1-C6) alkylaminocarbonyl;
- carbamoyl;
- linear, branched, or cyclic (C1-C6) alkylsulphonylamino;
- linear, branched, or cyclic (C1-C6) alkylsulphonyl;
- mono- or di-, linear, branched, or cyclic (C1-C6) alkylsulphamoyl;
- linear, branched or cyclic (C1-C6) alkoxy-(C1-C6) alkyl;
- wherein, two substituents may be taken together with their intervening atoms to form a ring;
- and
- (b) treating said compound of formula I-1 with hydrochloric acid in a ternary solvent solvent system to form a compound of formula I-1′:
28 more elements
A method comprising the steps of:
- (a) providing a compound of formula C′:
- and
- (b) treating said compound of formula C′ in the presence of a suitable base with a compound of formula F′:
- wherein LG2 and LG3 are suitable leaving groups, to form a compound of formula B′:
- and
- (c) treating said compound of formula B′ with a compound of formula G′:
- optionally in the presence of a suitable base and/or additive, to form compound I-1:
- and
- (d) treating said compound of formula I-1 with hydrochloric acid in a ternary solvent solvent system to form a compound of formula I-1′:
- wherein Ring A is a 4-8 membered saturated ring, having 0-2 heteroatoms independently selected from O, N, or S in addition to the nitrogen depicted in Ring A, wherein Ring A is independently substituted with 0-4 R′ groups;
- R′ is selected from the group consisting of mono- or di-[linear, branched or cyclic C1-6 alkyl]aminocarbonyl;
- linear, branched or cyclic C1-6 alkyl, alkoxy, or acyl;
- Y and Y′ are each independently N or C, with the proviso that at least one of Y or Y′ is N;
- T is a C3-5 bivalent hydrocarbon chain, optionally carrying an oxo group and optionally substituted with one or more halogen, hydroxy, C1-5 alkyl, alkoxy, fluoroalkyl, hydroxyalkyl, alkylidene, or fluoroalkylidene groups;
- C3-6 cycloalkane-1,1-diyl, oxacycloalkane-1,1-diyl, C3-6 cycloalkane-1,2-diyl, or oxacycloalkane-1,2-diyl groups, wherein the bonds of the 1,2-diyl radical form a fused ring with the T chain;
- and with the proviso that when T carries an oxo group, said oxo group is not part of an amide bond;
- and
- Ar is a group selected from 6-10 membered aryl, or 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;
- wherein Ar is optionally substituted with one or more substituents independently selected from halogen;
- hydroxy;
- mercapto;
- cyano;
- nitro;
- amino;
- sulfonyl;
- linear, branched or cyclic (C1-C6) alkyl, trihaloalkyl, di- or trihaloalkoxy, alkoxy, or alkylcarbonyl;
- (C3-C6) cycloalkyl-(C1-C6) alkoxy;
- (C3-C6) cycloalkyl-(C1-C6) alkyl;
- linear, branched, or cyclic (C1-C6) alkylcarbonylamino;
- mono- or di-, linear, branched, or cyclic (C1-C6) alkylaminocarbonyl;
- carbamoyl;
- linear, branched, or cyclic (C1-C6) alkylsulphonylamino;
- linear, branched, or cyclic (C1-C6) alkylsulphonyl;
- mono- or di-, linear, branched, or cyclic (C1-C6) alkylsulphamoyl;
- linear, branched or cyclic (C1-C6) alkoxy-(C1-C6) alkyl;
- wherein, two substituents may be taken together with their intervening atoms to form a ring;
- wherein each step is performed sequentially without isolation of intermediates B′ or I-1.
34 more elements
Dependencies are inferred from the claim text.