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US 12,583,840 B2Granted
Method for the preparation of androgen receptor antagonists and intermediates thereof
AssigneeOrion Corporation
InventorsArne Grumann, Oskari Karjalainen
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Abstract
The present invention relates to an improved process for the preparation of 2-chloro-4-(1-tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile (III) which is useful as an intermediate in preparation of carboxamide structured androgen receptor antagonists. The process comprises preparation of compound (III) using heterogeneous palladium catalyst.
Claims21
A method for the preparation of 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile of formula (III)
- comprising reacting a compound of formula (Ia) or (Ib)
- wherein R1 and R2 are hydrogen, or R1 and R2 together form a straight or a branched C2-6 alkyl chain or a —C(O)—CH2—N(CH3)—CH2—C(O)— chain,
- with 4-bromo-2-chlorobenzonitrile of formula (II)
- at an elevated temperature in the presence of a heterogeneous palladium catalyst, a solvent comprising dimethyl sulfoxide (DMSO), and a base.
1 more element
A method for the preparation of 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile of formula (V)
- comprising the steps of:
- (a) reacting a compound of formula (Ia) or (Ib)
- wherein R1 and R2 are hydrogen, or R1 and R2 together form a straight or a branched C2-6 alkyl chain or a —C(O)—CH2—N(CH3)—CH2—C(O)— chain,
- with 4-bromo-2-chlorobenzonitrile of formula (II)
- at an elevated temperature in the presence of heterogeneous palladium catalyst, a solvent comprising dimethyl sulfoxide (DMSO), and a base to obtain a compound of formula (III)
- (b) treating the compound of formula (III) with HCl;
- (c) adding a base to obtain the compound of formula (V).
4 more elements
A method for the preparation of the compound of formula (1A)
- comprising the steps of:
- (a) reacting a compound of formula (Ia) or (Ib)
- wherein R1 and R2 are hydrogen, or R1 and R2 together form a straight or a branched C2-6 alkyl chain or a —C(O)—CH2—N(CH3)—CH2—C(O)— chain,
- with 4-bromo-2-chlorobenzonitrile of formula (II)
- at an elevated temperature in the presence of a heterogeneous palladium catalyst, a solvent comprising dimethyl sulfoxide (DMSO), and a base to obtain a compound of formula (III)
- (b) treating the compound of formula (III) with HCl;
- (c) adding a base to obtain the compound of formula (V)
- (d) reacting a compound of formula (V) with a compound of formula (VI)
- to produce a compound of formula (VII)
- (e) reacting the compound of formula (VII) with a compound of formula (VIII)
- to produce a compound of formula (IX)
- and
- (f) reducing the compound of formula (IX) to produce the compound of formula (1A).
10 more elements
Dependencies are inferred from the claim text.