Iodine(II)-mediated radiofluorination

Patent metadata

Field	Value
Publication number	US-9957231-B2
Application number	US-201615231470-A
Country	US
Kind code	B2
Filing date	Aug 8, 2016
Priority date	Mar 7, 2014
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

A process for fluorination of aromatic compounds employing iodonium ylides and applicable to radiofluorination using 18 F is described. Processes, intermediates, reagents and radiolabelled compounds are described.

First claim

What is claimed is:

1. A process for fluorodeiodination of an aromatic iodide compound comprising:
(a) oxidizing an aromatic iodide compound (Ar-I), to form an iodonium compound;
(b) reacting the iodonium compound with a compound of formula (A):

to form an iodonium ylide;
(c) reacting the iodonium ylide with a fluoride source to form an aromatic fluoride compound (Ar-F);
wherein:
R A and R B in combination, together with the carbon atom to which R A and R B are attached, form a 3, 4, 5, 6, or 7-membered carbocyclic or a heterocyclic ring containing 3 to 7 carbon atoms and 0, 1, or 2 ring heteroatoms, each independently selected from N, O, and S, wherein the ring formed by the combination of R A and R B is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, and oxo.

2. The process of claim 1 , wherein step (a) is performed in the presence of an oxidizing agent selected from the group consisting of sodium perborate, urea-hydrogen peroxide adduct, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor®), potassium peroxymonosulfate (OXONE®), dimethyldioxirane, or meta-chloroperoxybenzoic acid.

3. The process of claim 2 , wherein step (a) is performed in the presence of a carboxylate source that is an acetate source or trifluoroacetate source.

4. The process of claim 1 , wherein said iodonium product of step (a) is an iodonium compound of Formula B or Formula C:

wherein Ar is an aromatic group, wherein Ar is connected to the iodonium group through an aromatic ring carbon atom.

5. The process of claim 1 , wherein step (b) is carried out in the presence of a base.

6. The process of claim 1 , wherein said iodonium ylide formed in step (b) is an iodonium ylide of Formula D:

wherein Ar is an aromatic group, wherein Ar is connected to the iodonium group through an aromatic ring carbon atom.

7. The process of claim 1 , wherein the compound of Formula A is a compound of the following formula:

8. The process of claim 1 , wherein the compound of Formula A is a compound of the following formula:

9. The process of claim 1 , comprising isolating or purifying the iodonium ylide following step (b).

10. The process of claim 1 , wherein said fluoride source of step (c) is a fluoride salt.

11. The process of claim 1 , wherein said fluoride source comprises [ 18 F] fluoride.

12. The process of claim 11 , wherein said fluoride source is tetraethylammonium [ 18 F]fluoride.

13. A compound of Formula D:

wherein:
Ar is an aromatic group; and
R A and R B in combination, together with the carbon atom to which R A and R B are attached, form a 3, 4, 5, 6, or 7-membered carbocyclic or a heterocyclic ring containing 3 to 7 carbon atoms and 0, 1, or 2 ring heteroatoms, each independently selected from N, O, and S, wherein the ring formed by the combination of R A and R B is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, and oxo; and
wherein Ar is connected to the iodonium group through an aromatic ring carbon atom.

14. The compound of claim 13 , wherein the compound of Formula D is a compound of the following formula:

15. The compound of claim 13 , wherein the compound of Formula D is a compound of the following formula:

16. A process for preparing a compound according to claim 13 comprising:
(a) oxidizing an aromatic iodide compound (Ar-I), to form an iodonium compound;
(b) reacting the iodonium compound with a compound of formula (A):

wherein Z 1 , Z 2 , R A and R B are as defined in claim 13 , to form a compound according to claim 13 .

17. A process for preparing an aromatic fluoride compound (Ar-F) comprising
(c) reacting a compound according to claim 13 with a fluoride source to form an aromatic fluoride compound.

18. The process of claim 17 , wherein said fluoride source of step (c) is a fluoride salt.

19. The process of claim 17 , wherein said fluoride source comprises [ 18 F] fluoride.

20. The process of claim 19 , wherein said fluoride source is tetraethylammonium [ 18 F]fluoride.

21. The process of claim 1 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached, form a 3, 4, 5, 6, or 7-membered carbocyclic ring, wherein the ring formed by the combination of R A and R B is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, and oxo.

22. The compound of claim 13 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached, form a 3, 4, 5, 6, or 7-membered carbocyclic ring, wherein the ring formed by the combination of R A and R B is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, and oxo.

23. The process of claim 1 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached form a cyclobutyl, cyclopentyl, or cyclohexyl ring.

24. The compound of claim 13 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached form a cyclobutyl, cyclopentyl, or cyclohexyl ring.

25. The process of claim 1 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached form a cyclopentyl ring.

26. The compound of claim 13 , wherein R A and R B in combination, together with the carbon atom to which R A and R B are attached form a cyclopentyl ring.

27. The process of claim 1 , wherein the compound of Formula A is a compound of the following formula:

28. The compound of claim 13 , wherein the compound of Formula D is a compound of the following formula:

Assignees

• Massachusetts Gen Hospital

Inventors

• Vasdev Neil
• Rotstein Benjamin H
• Stephenson Nickeisha A
• Liang Huan

Classifications

• C07D239/553

  with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil · CPC title

• C07J1/0059

  substituted in position 17 by a keto group · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07J17/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton (cardanolide, bufanolide C07J19/00) · CPC title

• C07D319/06

  not condensed with other rings · CPC title