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Method for halogenating or radiohalogenating a chemical compound

a chemical compound and radiohalogenation technology, applied in the field of labeling a chemical compound, can solve the problems of many difficulties in synthesizing desired radiohalogenated compounds, limited availability of suitable organic starting materials for radiolabeling reaction, and inability to work well on small scales

Inactive Publication Date: 2006-05-11
UNIV OF TENNESSEE RES FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach provides high radiochemical purity and yield, exceeding 75% in many cases, and allows for the attachment of radiolabels at any stage, overcoming the limitations of traditional methods by using stable organotrifluoroborates and enabling the synthesis of radiolabeled compounds with complex functional groups.

Problems solved by technology

A major disadvantage of such substitution reactions is that, because the reaction rates are dependent upon the concentration of reagents, the radiohalogenation reactions do not work well on small scales.
Consequently, one encounters many difficulties in synthesizing desired radiohalogenated compounds such as the rate of formation, separation of radiolabeled product from the organic starting material and side reactions such as solvent attack on the organic starting material.
Still another drawback is that the availability of suitable organic starting materials for the radiolabeling reaction is often limited.
An extremely important consequence of the above mentioned reaction rate problem is that no-carrier-added reagents are difficult to prepare.
However, the use of boronic acids as organohalogen precursors to pharmaceuticals has a disadvantageous propensity to form boroxines that are unstable to both air and water.
One disadvantage of most of the prior art methods of radiolabeling is that they require introduction of a radioisotope early in the construction of the desired molecule due to the fact that the methodologies do not tolerate many pharmacologically active functional groups.
This is deleterious because many of isotopes of use in medicine have very short half-lives and will decay before synthesis is complete.

Method used

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  • Method for halogenating or radiohalogenating a chemical compound
  • Method for halogenating or radiohalogenating a chemical compound
  • Method for halogenating or radiohalogenating a chemical compound

Examples

Experimental program
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Effect test

example 1

Production of Organotrifluoroborates

[0035] The procedure for obtaining organotrifluoroborate salts is shown schematically in Scheme 2.

[0036] A solution of a starting organic compound, such as phenylacetylene, (1.02 g, 10.0 mmol) in 20 mL of dry THF was cooled to −78° C. under argon. n-Butyllithium (6.25 mL, 1.60 M in hexane, 10 mmol) was added dropwise and the solution was stirred for one hour. Trimethylborate (1.58 g, 15.0 mmol, 1.5 equiv) was then added dropwise at −78° C. and the solution stirred for one hour. The reaction mixture was then allowed to warm to −20° C. and stirred for an additional hour. A saturated aqueous solution of potassium hydrogen difluoride (4.70 g, 60.0 mmol, 6 equivalents) was added to the vigorously stirred solution. The resulting mixture was allowed to stir for one hour at −20° C., after which it was allowed to warm to room temperature. The solvent was removed under reduced pressure and the resulting white solid was dried under high vacuum for two hou...

example 2

Synthesis of Aryl Iodides

[0038] A variety of aryltrifluoroborates, synthesized as described in Example 1, were subjected to radioiodination using no-carrier added Na123I and peracetic acid in 50% aqueous THF to yield the corresponding aryliodides. The general formula for this reaction is shown below in Scheme 3. All reactions were carried out using dry solvents under an inert atmosphere.

example 2a

Radiosynthesis of 4-[123I]iodoanisole (Representative Procedure)

[0039] Para-methoxyphenyltrifluoroborate (100 μL of 5.2×10−2 solution in 50% aqueous tetrahydrofuran) was placed in a 2 mL Wheaton vial containing no-carrier-added Na123, (37 MBq in 0.1% aqueous NaOH). To this was added peracetic acid (100 μL, 0.3% solution in methanol). The reaction vial was sealed, covered with aluminum foil, and the mixture stirred for 10 min at room temperature. A drop of 10% aqueous sodium thiosulfite was added to decompose excess iodine and the radioiodinated product was isolated by passing it through a silica gel Sep-Pak cartridge using petroleum ether:ethyl acetate (50:1) as eluent. The radiochemical purity of 4-[123I]iodoanisole was determined by radio-TLC (aluminum backed silica gel plate, hexane:ethyl acetate=50:1); Rf=0.55. The TLC retention time (and that of all products) was identical to that of authentic samples. The radiochemical purity was 98% and the radiochemical yield was 88%. The t...

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Abstract

A method for obtaining a halogenated organic compound, whereby an organotrifluoroborate compound is reacted with a halide ion in the presence of an oxidizing agent to produce the corresponding halogenated organic compound. The method may be used for producing radiohalogenated organic compounds.

Description

[0001] This application claims the benefit of pending U.S. Provisional Application Ser. No. 60 / 608,186, which was filed on Sep. 9, 2004.[0002] This invention was developed in part by grants from the U.S. Department of Energy and the National Institutes of Health and the U.S. government may have certain rights in the invention.FIELD OF THE INVENTION [0003] This invention pertains to the field of labeling a chemical compound, and particularly to the field of attaching a halogen label, such as a radioactive halogen, to an organic chemical compound. BACKGROUND OF THE INVENTION [0004] Radioisotopes, particularly halogen radioisotopes, have been used extensively in nuclear medicine. The preferred utility of radioiodine in nuclear medicine is based on the availability of relatively reliable techniques of incorporating radiohalogen atoms into organic compounds. [0005] Many of the presently available radiohalogenation techniques have the common feature that a radionuclide is introduced into ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07C19/08
CPCC07B39/00C07B59/00C07C17/093C07C45/63C07C201/12C07C253/30C07C25/22C07C19/16C07C21/22C07C21/17C07C25/02C07C25/24C07C22/00C07C49/807C07C255/50C07C205/12
Inventor KABALKA, GEORGE W.
Owner UNIV OF TENNESSEE RES FOUND
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