Isotopically enriched N-substituted piperazine acetic acids and methods for the preparation thereof

• US 7,355,045 B2
• Filed: 01/05/2004
• Issued: 04/08/2008
• Est. Priority Date: 01/05/2004
• Status: Active Grant

• Current Assignee: DH Technologies Pte. Ltd.
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Coull, James M., Pappin, Darryl J. C., Purkayastha, Subhasish, Dey, Subhakar, Pillai, Sasi
• Primary Examiner(s): Wilson; James O.
• Assistant Examiner(s): SACKEY, EBENEZER O
• Application Number:
  US10/751,387
• Publication Number:
  US 20050148774A1
• Time in Patent Office: 1,555 Days
• Field of Search: 544/399
• US Class Current: 544/399
• CPC Class Codes: C07D 295/03 with the ring nitrogen atoms directly attached to acyclic carbon atoms
• CPC Class Codes: C07D 295/15 to an acyclic saturated chain
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links

Abstract

In some embodiments, this invention pertains to isotopically enriched N-substituted piperazine acetic acids. In some embodiments, this invention pertains to methods for the preparation of isotopically enriched N-substituted piperazine acetic acids.

Claims

1. An isotopically enriched N-substituted piperazine acetic acid compound of the formula:

2. The compound of claim 1, wherein the N-substituted piperazine acetic acid is isotopically enriched with two or more heavy atom isotopes.

3. The compound of claim 1, wherein the N-substituted piperazine acetic acid is isotopically enriched with three or more heavy atom isotopes.

4. The compound of claim 1, wherein the N-substituted piperazine acetic acid is isotopically enriched with four or more heavy atom isotopes.

5. The compound of claim 2, wherein the heavy atom isotopes are each independently ¹⁸O, ¹⁵N or ¹³C, but not deuterium.

6. The compound of claim 1, wherein each Z is independently hydrogen, fluorine, chlorine, bromine or iodine.

7. The compound of claim 1, wherein each Z is independently hydrogen, methyl or methoxy.

8. The compound of claim 1, wherein Y is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

9. The compound of claim 1, wherein X is ¹⁶O or ¹⁸O.

10. The compound of claim 1, wherein each nitrogen atom of the piperazine ring is independently ¹⁴N or ¹⁵N.

11. The compound of claim 1 of the formula:

12. The compound of claim 1 of the formula:

13. The compound of claim 12, wherein the compound is a zwitterion, mono-TFA salt, a mono-HCl salt, a bis-TFA salt or a bis-HCl salt.

14. The compound of claim 12, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

15. The compound of claim 12, wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.

16. The compound of claim 12, wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.

17. The compound of claim 1, wherein the N-substituted piperazine acetic acid is a mono-TFA salt, a mono-HCl salt, a bis-HCl salt or a bis-TFA salt.

18. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

19. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.

20. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.

21. The compound of claim 12, wherein the compound is a carboxylate anion.

22. The compound of claim 1, wherein the compound is a carboxylate anion.

23. An isotopically enriched N-substituted piperazine acetic acid compound of the formula:

24. The compound of claim 23, wherein Y is a straight chain or branched C1-C6 alkyl group and each Z is independently hydrogen, fluorine , chlorine, bromine, iodine, an amino acid side chain or a straight chain or branched C1-C6 alkyl group.

25. An isotopically enriched N-substituted piperazine acetic acid compound of the formula:

26. An isotopically enriched N-substituted piperazine acetic acid compound of the formula: