Making and Separating Specific Chemical Forms of a Drug Compound

This patent describes a method to convert a specific chemical compound into a balanced mixture of its mirror-image forms and then separate one desired form, important for making medicines.

What it covers

This patent provides a method for making and separating specific chemical forms of a complex molecule referred to as 'Compound A' (7-chloro-6-fluoro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-D]pyrimidine-2,4(1H,3H)-dione). One process involves heating a composition containing the (P)-form of Compound A, or its salt, with a solvent to a high temperature, specifically between 250° C. and 350° C. This heating step converts the pure (P)-form into a mixture of both mirror-image forms, known as racemized Compound A. Additionally, the patent describes a process for isolating the desired (P)-Compound A from a mixture that includes a tartrate, which helps in the separation. It also details a method for isolating the free acid of a tartrate or its hydrate from a composition containing the tartrate, (P)-Compound A, and an organic solvent. For example, a pharmaceutical company could use this process to ensure a drug contains only the effective (P)-Compound A, avoiding the inactive or harmful mirror-image form.

What it doesn't cover

• —Does not cover racemization processes for chemical compounds other than 7-chloro-6-fluoro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-D]pyrimidine-2,4(1H,3H)-dione.
• —Does not cover racemization of (P)-compound A at temperatures outside the specified range of 250° C. to 350° C.
• —Does not cover isolation methods for (P)-compound A that do not involve the use of a tartrate.
• —Does not cover separation of other types of isomers, such as enantiomers that are not atropisomers, or diastereomers.
• —Does not cover processes for isolating (P)-compound A from compositions that do not contain a tartrate.

The clever bit

The novelty likely lies in discovering the precise high-temperature conditions (250-350°C) required to efficiently convert a specific atropisomer into a racemic mixture, and then a specific method using tartrates to isolate the desired pure form of Compound A.

Why it matters

In drug development, often only one specific mirror-image form of a molecule, called an atropisomer, has the desired therapeutic effect while the other form might be inactive or even harmful. This patent provides methods to ensure that the correct form of a specific compound, 'Compound A', is produced and separated efficiently for pharmaceutical use. This precision is critical for drug safety and effectiveness.

Real-world examples

• 1.Pharmaceutical manufacturing of specific drug components
• 2.High-temperature chemical synthesis processes for chiral molecules