Synthesis of abiraterone and related compounds
AssigneeCrystal Pharma, S.A.U.
InventorsAlfonso Perez Encabo, Jose Angel Turiel Hernandez, Francisco Javier Gallo Nieto, Antonio Lorente Bonde-Larsen, Celso Miguel Sandoval Rodriguez
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Abstract
The present invention relates to processes for obtaining abiraterone and derivatives thereof, such as abiraterone acetate, by means of a Suzuki coupling through a steroid borate of general formula (IV) or a C—C coupling through a steroid hydrazone of general formula (II), as well as to intermediates useful in said processes.
Claims21
A process for obtaining a compound of formula (I)
- or a salt or solvate thereof, wherein
- R1 is selected from the group consisting of H and a hydroxyl protecting group;
- comprising reacting a compound of formula (IV)
- wherein
- R1 is selected from the group consisting of H and a hydroxyl protecting group;
- and
- Z and Z′ are independently selected from the group consisting of hydroxyl, optionally substituted C1-C8 alkoxy and optionally substituted C1-C8 alkyl, or Z and Z′ together form an optionally substituted C2-C3 alkylenedioxy group or an optionally substituted C6 aryldioxy group;
- with a compound of formula (III)
- wherein
- X is halogen or OSO2CF3.
- in the presence of a palladium catalyst and a base.
A process for obtaining a compound of general formula (I)
- or a salt or solvate thereof,
- wherein
- R1 is selected from the group consisting of H, and a hydroxyl protecting group;
- comprising reacting a compound of general formula (II)
- wherein
- R1 has the previously mentioned meanings, R2 is SO2R7 and R7 is selected from the group consisting of optionally substituted C1-C8 alkyl and optionally substituted C6-C14 aryl;
- with a compound of formula (III)
- wherein
- X is halogen or OSO2CF3;
- in the presence of a palladium catalyst and a base.
An intermediate compound selected from:
- a) a compound of formula (II)
- or a salt or solvate thereof, wherein
- R1 is selected from the group consisting of H and a hydroxyl protecting group;
- R2 is SO2R7;
- R7 is selected from the group consisting of optionally substituted C1-C8 alkyl and optionally substituted C6-C14 aryl;
- with the proviso that the following compounds are not included:
- b) a compound of formula (IX)
- or a salt or solvate thereof, wherein
- R1 is a hydroxyl protecting group, and
- X′ is bromo or iodo;
- c) a compound of formula (V)
- or a salt or solvate thereof, wherein
- R1 is a hydroxyl protecting group;
- and
- d) a compound of formula (IV)
- or a salt or solvate thereof, wherein
- R1 is selected from the group consisting of H and a hydroxyl protecting group;
- and
- Z and Z′ are independently selected from the group consisting of hydroxyl, optionally substituted C1-C8 alkoxy and optionally substituted C1-C8 alkyl, or Z and Z′ together form an optionally substituted C2-C3 alkylenedioxy group or an optionally substituted C6 aryldioxy.
A compound of formula (I)
- or a salt or solvate thereof,
- wherein
- R1 is SiR3R4R5. and
- R3, R4 and R5 are independently selected from the group consisting of optionally substituted C1-C8 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C6-C14 aryl, optionally substituted C1-C8 alkoxy, and halogen.
A compound of formula:
Dependencies are inferred from the claim text.