Metal oxide catalyzed radiofluorination

Patent metadata

Field	Value
Publication number	US-9895454-B2
Application number	US-201515323046-A
Country	US
Kind code	B2
Filing date	Jul 2, 2015
Priority date	Jul 3, 2014
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

Inter alia, the first titania-catalyzed [ 18 F]-radiofluorination in highly aqueous medium is provided. In embodiments, the method utilizes titanium dioxide, 1:1 acetonitrile-thexyl alcohol solvent mixture and tetrabutylammonium bicarbonate as a base. Radiolabeling may be directly performed with aqueous [ 18 F]fluoride without the need for drying/azeotroping step, which reduces radiosynthesis time while keeping high fluoride conversion. The general applicability of the synthetic strategy to the synthesis of the wide range of PET probes from tosylated precursors is demonstrated.

First claim

What is claimed is:

1. A method of forming an [ 18 F]-labeled organic compound in an aqueous medium, the method comprising:
combining within an aqueous medium an aqueous [ 18 F] fluoride, a transition metal oxide and an organic compound precursor comprising a reactive carbon; and
allowing said aqueous [ 18 F] fluoride source to react with said reactive carbon thereby forming said [ 18 F]-labeled organic compound,
wherein said transition metal oxide is chromium(VI) oxide, molybdenum(VI) oxide, platinum(IV) oxide, rhenium(VI) oxide, rhenium(VII) oxide, ruthenium(IV) oxide, tantalum(V) oxide, tin(IV) oxide, vanadium(IV) oxide, vanadium(V) oxide, yttrium(III) oxide, zirconium(IV) oxide, chromium(III) oxide, bismuth(III) oxide, manganese(IV) oxide, tungsten(IV) oxide, molybdenum(IV) oxide, tungsten(VI) oxide, palladium(II) oxide, iron(II) oxide, zinc(II) oxide, indium(III) oxide, copper(II) oxide, niobium(IV) oxide, niobium(V) oxide, or titanium(IV) oxide.

2. The method of claim 1 , wherein said organic compound precursor is an aryl organic compound precursor and said [ 18 F]-labeled organic compound is an [ 18 F]-labeled aryl organic compound.

3. The method of claim 1 , wherein said aqueous medium is less than about 5%, 10%, 15%, 20% or 25% water.

4. The method of claim 1 , wherein said [ 18 F]-labeled organic compound is a positron emission tomography probe.

5. The method of claim 1 , wherein said reacting is SN2 nucleophilic substitution reacting.

6. The method of claim 1 , wherein the reactive carbon forms part of a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocycloalkyl.

7. The method of claim 1 , wherein the reactive carbon forms part of a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocycloalkyl.

8. The method of claim 1 , wherein said transition metal oxide is palladium(II) oxide, iron(II) oxide, zinc(II) oxide, indium(III) oxide, copper(II) oxide, niobium(IV) oxide, niobium(V) oxide, or titanium(IV) oxide.

9. The method of claim 1 , wherein said transition metal oxide is TiO 2 , NbO 2 , Nb 2 O 5 , In 2 O 3 , or CuO.

10. The method of claim 1 , wherein said aqueous medium further comprises a base.

11. The method of claim 1 , wherein said aqueous medium further comprises an ammonium base.

12. The method of claim 1 , wherein said aqueous medium further comprises an ammonium bicarbonate base.

13. The method of claim 1 , wherein said aqueous medium further comprises an alcohol co-solvent, optionally MeOH, EtOH, n-PrOH, i-PrOH, t-BuOH, tHexOH, n-octanol or cyclohexanol.

14. The method of claim 1 , wherein said aqueous medium further comprises an alcohol co-solvent, optionally t-BuOH, tHexOH, n-octanol or cyclohexanol.

15. The method of claim 1 , wherein said organic compound precursor is attached to a tosylate, benzenesulfonyl, 4-nitrobenzenesulfonyl, methanesulfonyl, ethanesulfonyl, trifluoromethylsulfonyl, or 1,1,2,2,2-pentafluoroethane-1-sulfonyl moiety.

16. The method of claim 1 , wherein said aqueous [ 18 F] fluoride is generated from a cyclotron and is not dried or azeotroped after generation from said cyclotron.

Assignees

• Univ California

Inventors

• Sergeev Maxim
• Morgia Federica
• Van Dam Robert Michael
• Lazari Mark

Classifications

• A61K51/04 Primary

  Organic compounds · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07C17/361

  by reactions involving a decrease in the number of carbon atoms · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title