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US 12,747,226 B2Granted
Method of preparing Pralsetinib
AssigneeRigel Pharmaceuticals, Inc.
InventorsJoshua Waetzig, Gordon D. Wilkie, Vincent Poral, Albert Cornelis Dros
Life of this patent
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Abstract
Provided herein, in part, are compounds and compositions useful for preparing pralsetinib. Also provided herein are processes for preparing pralsetinib.
Claims20
A compound selected from the group consisting of:
- a compound of Formula (I):
- or a salt thereof;
- a compound of Formula (II):
- or a salt thereof;
- and
- a compound of Formula (III):
- or a salt thereof.
4 more elements
A compound of Formula V:
- or a salt thereof.
A composition comprising a compound of Formula VI:
- or a salt thereof, wherein the composition comprises the compound of Formula (VI) or a salt thereof and the compound of Formula (VIa) or a salt thereof in a ratio of greater than or equal to about 9:1:
- or a salt thereof.
A composition comprising a compound of Formula (VII):
- or a salt thereof, wherein the composition comprises the compound of Formula (VII) or a salt thereof and the compound of Formula (VIIa) or a salt thereof in a ratio of greater than or equal to about 9:1:
- or a salt thereof.
A process of preparing a composition comprising a mixture of cis and trans isomers of a compound of Formula (IV):
- or a salt thereof, wherein the process comprises:
- (a) reacting a compound of Formula (II):
- or a salt thereof with an ammonium source in the presence of a solvent, thereby producing a compound of Formula (III):
- or a salt thereof;
- and
- (b) reacting a compound of Formula (III) with alkyl acetoacetate, thereby producing a composition comprising a mixture of cis and trans isomers of a compound of Formula (IV) having a greater amount of the cis isomer, Formula (IVa):
- or a salt thereof, as compared to the trans isomer, Formula (IVb):
- or a salt thereof.
5 more elements
A process of preparing a compound of Formula (X):
- or a salt thereof, comprising the steps of:
- (a) reacting a compound of Formula (II):
- or a salt thereof with an ammonium source in the presence of a solvent, thereby producing a compound of Formula (III):
- or a salt thereof;
- (b) reacting a compound of Formula (III) with alkyl acetoacetate, thereby producing an isomeric mixture of a compound of Formula (IV):
- or a salt thereof, wherein the isomeric mixture of the compound of Formula (IV) has a greater amount of the cis isomer, Formula (IVa):
- or a salt thereof, as compared to the trans isomer, Formula (IVb):
- or a salt thereof;
- (c) purifying the isomeric mixture of the compound of Formula (IV) or a salt thereof to obtain the compound of Formula (IVa) or a salt thereof;
- (d) reacting the compound of Formula (IVa) or a salt thereof with an activating agent, thereby providing a compound of Formula (V-1a):
- or a salt thereof, wherein R is an activating group;
- (e) reacting the compound of Formula (V-la) or a salt thereof with 5-methyl-3-pyrazolamine, thereby providing a compound of Formula (VI):
- or a salt thereof;
- (f) reacting the compound of Formula (VI) or a salt thereof with a base, thereby providing a compound of Formula (VII):
- or a salt thereof;
- (g) reacting the compound of Formula (VII) or a salt thereof with a compound of Formula (VIII):
- or a salt thereof, thereby providing the compound of Formula (X) or a salt thereof.
14 more elements
An isomeric mixture of cis and trans isomers of a compound of Formula (IV):
- or a salt thereof, wherein the cis isomer is a compound of Formula (IVa):
- and the trans isomer is a compound of Formula (IVb):
- or a salt thereof, wherein the ratio of the cis isomer to the trans isomer is greater than or equal to about 5:1.
Dependencies are inferred from the claim text.