Isotopically enriched N-substituted piperazines and methods for the preparation thereof

• US 7,307,169 B2
• Filed: 01/05/2004
• Issued: 12/11/2007
• Est. Priority Date: 01/05/2004
• Status: Active Grant

• Current Assignee: DH Technologies Pte. Ltd.
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Pappin, Darryl J. C., Pillai, Sasi, Coull, James M.
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): SACKEY, EBENEZER O
• Application Number:
  US10/751,388
• Publication Number:
  US 20050148773A1
• Time in Patent Office: 1,436 Days
• Field of Search: 544/358, 544/392, 544/398, 544/399
• US Class Current: 544/358
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 241/08 with oxygen atoms directly attached to ring carbon atoms
• CPC Class Codes: C07D 253/08 condensed with carbocyclic rings or ring systems
• 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

Abstract

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

Claims

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

2. The compound of claim 1, wherein the N-substituted piperazine is isotopically enriched with two or more atoms of ¹³C and/or ¹⁵N.

3. The compound of claim 1, wherein the N-substituted piperazine is isotopically enriched with three or more atoms of ¹³C and/or ¹⁵N.

4. The compound of claim 1, wherein the N-substituted piperazine is isotopically enriched with four or more atoms of ¹³C and/or ¹⁵N.

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

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

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

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

9. The compound of claim 1 of the formula:

10. The compound of claim 9, wherein the compound is a mono-TFA salt, a mono-HCl salt, a bis-TFA salt or a bis-HCl salt.

11. The compound of claim 9, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

12. The compound of claim 9, wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.

13. The compound of claim 9, wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.

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

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

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

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

18. An isotopically enriched N-substituted piperazine compound of the formula:

19. The compound of claim 18, wherein each Z is hydrogen.

20. An isotopically enriched N-substituted piperazine compound of the formula:

21. An isotopically enriched N-substituted piperazine compound of the formula:

22. An isotopically enriched N-substituted piperazine compound of the formula: