Isotopically enriched N-substituted piperazines and methods for the preparation thereof
View Patent ↗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.
1. An isotopically enriched N-substituted piperazine compound of the formula:
, or a salt thereof, comprising one or more heavy atom isotopes, wherein;
Y is a straight chain or branched C1-C6 alkyl group or a straight chain or branched C1-C6 alkyl ether group wherein the carbon atoms of the alkyl group or alkyl ether group each independently comprise linked hydrogen, deuterium or fluorine atoms; and
each Z is independently hydrogen, fluorine, chlorine, bromine, iodine, an amino acid side chain, a straight chain or branched C1-C6 alkyl group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently comprise linked hydrogen or fluorine atoms, a straight chain or branched C1-C6 alkyl ether group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently comprise linked hydrogen or fluorine atoms or a straight chain or branched C1-C6 alkoxy group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently comprise linked hydrogen or fluorine atoms;
wherein the N-methyl piperazine is isotopically enriched with either of 13 C and/or 15 N.
2. The compound of claim 1 , wherein the N-substituted piperazine is isotopically enriched with two or more heavy atom isotopes.
3. The compound of claim 1 , wherein the N-substituted piperazine is isotopically enriched with three or more heavy atom isotopes.
4. The compound of claim 1 , wherein the N-substituted piperazine is isotopically enriched with four or more heavy atom isotopes.
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 14 N or 15 N.
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.