Process for the preparation of 1,3-substituted indenes and aryl-fused azapolycyclic compounds
AssigneePfizer Inc.
InventorsRobert Singer, Jason McKinley
Life of this patent
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Abstract
The present invention relates to processes for the preparation of any of the intermediate 1,3-substituted indenes of the formulae (Ia), (Ib) and (Ic) or a mixture thereof: wherein R1, R2, R3, R4, and R5 are defined herein. Compounds of formulae (Ia), (Ib) and (Ic) or mixtures thereof are useful in the preparation of compounds of formula (II): wherein R2, R3 and R6 are also defined herein.
Claims20
A process for the preparation of any one of the compounds of formulae (Ia) and (Ib) or a mixture thereof:
- wherein R2 and R3 are independently selected from the group consisting of hydrogen, fluoro, —CF3, and —OCH3;
- R1 is an electron withdrawing group selected from cyano and phenylsulfonyl;
- R4 is independently hydrogen, methyl, ethyl, or a metal cation Na;
- or two R4 groups together form a (C2-C3)alkylene bridge;
- R5 is methyl or ethyl;
- comprising the step of reacting a compound of formula (III)
- wherein R1, R2, R3, and R4 are as set forth above;
- and X′ is bromo or chloro, in the presence of a palladium catalyst and a base.
A process for the preparation of any one of compounds of the formulae (Ia) and (Ib) or a mixture thereof:
- wherein R2 and R3 are independently selected from the group consisting of hydrogen, fluoro, —CF3, and —OCH3;
- R1 is an electron withdrawing group selected from cyano and phenylsulfonyl;
- R4 is independently hydrogen, methyl, ethyl, or a metal cation Na;
- or two R4 groups together form a (C2-C3)alkylene bridge;
- R5 is methyl or ethyl;
- comprising the step of reacting a compound of formula (IV)
- wherein R5 is an electron withdrawing group selected from cyano and phenylsulfonyl;
- X′ is bromo or chloro;
- with a compound of formula (V):
- wherein R5 is as defined above;
- in the presence of a base and a palladium catalyst.
A process for the preparation of compounds of formula (VII):
- comprising the step of subjecting any one of compounds of the formulae (Ia) and (Ib) or a mixture thereof:
- to hydrogenolysis conditions;
- wherein R1 is CN or phenylsulfonyl;
- R2 and R3 are independently selected from the group consisting of hydrogen, fluoro, —CF3, and —OCH3;
- R5 is methyl or ethyl;
- and
- R4 is independently hydrogen, methyl, ethyl, or a metal cation Na;
- or two R4 groups together form a (C2-C3)alkylene bridge.
Dependencies are inferred from the claim text.