2,3-diaryl-1,3-thiazepan-4-ones compounds and methods for making

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to compounds with a seven-membered 1,3-thiazepan-4-one ring system.

In fact, nearly all of the known compounds with this ring system are related in structure to omapatrilat.

Because of their biological activity and potential medicinal use, there is a need for 2,3-diaryl-1,3-thiazepan-4-ones compounds and methods for making these compounds.

SUMMARY OF THE INVENTION

Embodiments of this invention are directed to 2,3-diaryl-1,3-thiazepan-4-one compounds.

One embodiment is directed to a compound of Formula I:

In another embodiment, at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9and R10is not hydrogen, and R13and R14are bonded to each other to form a cyclopropyl group.

In another embodiment, the compound is

In another embodiment, the compound is

In another embodiment, the compound is

In another embodiment, the compound is

In another embodiment, the compound is

DETAILED DESCRIPTION OF THE INVENTION

Definitions

While the terms used herein are believed to be well understood by one of ordinary skill in the art, definitions are set forth herein to facilitate explanation of the subject matter disclosed herein.

The terms “a,” “an,” and “the” refer to “one or more” when used in this application, including the claims. The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

All references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic(s) or limitation(s) and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.

The methods and devices of the present disclosure, including components thereof, can comprise, consist of, or consist essentially of the essential elements and limitations of the embodiments described herein, as well as any additional or optional components or limitations described herein or otherwise useful.

The term “alkyl” includes branched, straight chain and cyclic, substituted or unsubstituted saturated aliphatic hydrocarbon groups. Alkyl groups can comprise about 1 to about 24 carbon atoms (“C1-C24”), about 7 to about 24 carbon atoms (“C7-C24”), about 8 to about 24 carbon atoms (“C8-C24”), or about 9 to about 24 carbon atoms (“C9-C24”). Alkyl groups can also comprise about 1 to about 8 carbon atoms (“C1-C8”), about 1 to about 6 carbon atoms (“C1-C6”), or about 1 to about 3 carbon atoms (“C1-C3”). Examples of C1-C6 alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, cyclohexyl, cyclohexylinethyl, cyclopropylrnethyl and neohexyl radicals.

The term “aryl” includes a 6- to 14-membered monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring system. Examples of an aryl group include phenyl and naphthyl.

The term “aralkyl” refers to an aryl-alkyl group wherein aryl and alkyl are as previously described.

As used herein, the term “halogen” means F, Cl, Br or I.

The following description is of exemplary embodiments that are presently contemplated for carrying out the present invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles and features of the present invention. The scope of the present invention is not limited by this description.

The present invention is directed to a class of 2,3-diaryl-1,3-thiazepan-4-ones 1 and methods to make them.

A general synthetic scheme is as follows:

General Synthetic Procedure: A two-necked 25-mL round bottom flask was oven-dried, cooled under N2, and charged with a stir bar and an imine (6 mmol), or alternatively the precursor aldehyde and amine (6 mmol each). 2-Methyltetrahydrofuran (2.3 mL) was added and the solution was stirred. Pyridine (1.95 mL, 24 mmol) was added and then [1-(sulfanylmethyl)cyclopropyl] acetic acid (0.877 g, 6 mmol) was added. Finally, 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (T3P) in 2-methyltetrahydrofuran (50 weight percent; 7.3 mL, 12 mmol) was added. The reaction was stirred at room temperature and followed by TLC, then poured into a separatory funnel with dichloromethane (20 mL). The mixture was washed with water (10 mL). The aqueous was then extracted twice with dichloromethane (10 mL each). The organics were combined and washed with saturated sodium bicarbonate (10 mL) and then saturated sodium chloride (10 mL). The organic was dried over sodium sulfate and concentrated under vacuum to give a crude mixture. Further purification was carried out as indicated below for each compound.

Although the present invention has been described in terms of specific exemplary embodiments and examples, it will be appreciated that the embodiments disclosed herein are for illustrative purposes only and various modifications and alterations might be made by those skilled in the art without departing from the spirit and scope of the invention as set forth in the following claims.

REFERENCES

All references cited herein including those below are hereby incorporated by reference in their entirety.