Radioiodinated compounds

Patent metadata

Field	Value
Publication number	US-10053423-B2
Application number	US-201515109608-A
Country	US
Kind code	B2
Filing date	Jan 2, 2015
Priority date	Jan 3, 2014
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

This disclosure relates to reagents and methods useful in the synthesis of aryl iodines, for example, in the preparation of iodine labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

First claim

What is claimed is:

1. A method for making a compound of Formula (1):
Ar 2 —*I   1

wherein:
Ar 2 is an aryl or heteroaryl ring system; and
I* is a radioactive isotope of iodine;
wherein the radioactive isotope of iodine has a specific activity of at least about 1 mCi/mg;

the method comprising:
(a) reacting a mixture comprising a compound M*I, wherein M is a counter cation, and compound of Formula (2):

wherein:
Ar 1 is an aryl or heteroaryl ring system that is electron-rich as compared to Ar 2 ;
Y is a leaving group; and
Ar 2 is as defined above; and
(b) heating the reaction mixture from step (a).

2. The method of claim 1 , wherein the reaction mixture in step (a) further comprises a solvent.

3. The method of claim 2 , wherein the solvent is removed from the reaction mixture prior to step (b).

4. The method of claim 1 , wherein the reaction mixture in step (b) further comprises a solvent.

5. The method of claim 1 , wherein Ar 1 —H is more easily oxidized than benzene.

6. The method of claim 1 , wherein Ar 1 is substituted with at least one substituent having a Hammett σ p value of less than zero.

7. The method of claim 6 , wherein the substituent is selected from the group consisting of: —(C 1 -C 10 )alkyl, —(C 1 -C 10 )haloalkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, —O—(C 1 -C 10 )alkyl, —C(O)—O—(C 1 -C 10 )alkyl, aryl, and heteroaryl.

8. The method of claim 1 , wherein the radioactive isotope of iodine is selected from the group consisting of: 123 I, 124 I, 125 I, and 131 I.

9. The method of claim 1 , wherein Ar 1 is:

wherein:
R 1 , R 2 , R 3 , R 4 , and R 5 are independently selected from the group consisting of: H, —(C 1 -C 10 )alkyl, —(C 1 -C 10 )haloalkyl, ((C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, —O—(C 1 -C 10 )alkyl, —C(O)—O—(C 1 -C 10 )alkyl, aryl, and heteroaryl, or two or more of R 1 , R 2 , R 3 , R 4 , and R 5 come together to form a fused aryl or heteroaryl ring system.

10. The method claim 1 , wherein AP is selected from the group consisting of: a phenylalanine derivative, tyrosine derivative, tryptophan derivative, histidine derivative, and an estradiol derivative.

11. The method of claim 1 , wherein AP is selected from the group consisting of:

wherein each X is independently a protecting group.

12. The method of claim 11 , wherein Ar 2 is selected from the group consisting of:

13. The method of claim 1 , wherein Y is selected from the group consisting of: triflate, mesylate, nonaflate, hexaflate, tosylate, nosylate, brosylate, perfluoroalkyl sulfonate, tetraphenylborate, hexafluorophosphate, trifluoroacetate, tetrafluoroborate, perchlorate, perfluoroalkylcarboxylate, and chloride.

14. The method of claim 1 , wherein M is selected from the group consisting of: lithium, potassium, sodium, cesium, complexes of lithium, sodium, potassium, or cesium with cryptands or crown ethers, tetrasubstituted ammonium cations, and phosphonium cations.

15. The method of claim 1 , wherein the compound of Formula (2) is selected from the group consisting of:

wherein each Y is independently a leaving group as defined above; and
each X is independently a protecting group.

16. The method of claim 15 , wherein the compound of Formula (2) is selected from the group consisting of:

17. The method of claim 1 , wherein the compound of Formula (1) is selected from the group consisting of:

wherein each X is independently a protecting group.

18. The method of claim 17 , wherein the compound of Formula (1) is selected from the group consisting of:

19. A method for making a compound of Formula (1)
Ar 2 —*I   1

wherein:
Ar 2 is an aryl or heteroaryl ring system; and
*I is a radioactive isotope of iodine;
wherein the radioactive isotope of iodine has a specific activity of at least about 1 mCi/mg;

the method comprising heating a compound of Formula (3):

wherein:
Ar 1 is an aryl or heteroaryl ring system that is electron-rich as compared to Ar 2 ; and
Ar 2 is as defined above.

Assignees

• Nutech Ventures

Inventors

• Dimagno Stephen
• Hu Bao

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D207/404

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07C227/16

  by reactions not involving the amino or carboxyl groups · CPC title