Method of fluorination using iodonium ylides

Patent metadata

Field	Value
Publication number	US-10259800-B2
Application number	US-201615166063-A
Country	US
Kind code	B2
Filing date	May 26, 2016
Priority date	Oct 29, 2015
Publication date	Apr 16, 2019
Grant date	Apr 16, 2019

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; and
(c) reacting the iodonium ylide with a fluoride source to form an aromatic fluoride compound (Ar—F);
wherein:
Z 1 is selected from the group consisting of NR Z1 , O, and S;
Z 2 is selected from the group consisting of NR Z2 , O, and S;
R Z1 is selected from the group consisting of H, C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein said C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;
R Z2 is selected from the group consisting of H, C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein said C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;
R A and R B in combination, together with the carbon atom to which R A and R B are attached, form an 8, 9, or 10-membered carbocyclic or heterocyclic ring containing 8 to 10 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
each R 20 is independently selected from the group consisting of OH, SH, CN, NO 2 , halo, oxo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, —(C 1-4 alkyl)-(C 1-4 alkoxy), —(C 1-4 alkoxy)-(C 1-4 alkoxy), C 1-4 haloalkoxy, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, di(C 1-4 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-4 alkylaminocarbonylamino, and di(C 1-4 alkyl)aminocarbonylamino.

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), potassium peroxymonosulfate, dimethyldioxirane, or meta-chloroperoxybenzoic acid, and a carboxylate salt that is an acetate source or a trifluoroacetate source.

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

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

wherein Z 1 is O and Z 2 is O.

5. The process of claim 1 , wherein the compound of Formula A is selected from compounds of the following formulae:

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

7. The process of claim 1 , wherein the compound of Formula D is selected from compounds of the following formulae:

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

9. 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), potassium peroxymonosulfate, dimethyldioxirane, or meta-chloroperoxybenzoic acid, and a carboxylate salt that is an acetate source or a trifluoroacetate source, and step (b) is carried out in the presence of a carbonate base.

10. The process of claim 9 , wherein the compound of Formula A is a compound of the following formula:

11. The process of claim 10 , wherein said fluoride source comprises [ 18 F] fluoride.

12. A compound of Formula D:

wherein:
Ar is an aromatic group;
Z 1 is selected from the group consisting of NR Z1 , O, and S;
Z 2 is selected from the group consisting of NR Z2 , O, and S;
R Z1 is selected from the group consisting of H, C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein said C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;
R Z2 is selected from the group consisting of H, C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein said C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;
R A and R B in combination, together with the carbon atom to which R A and R B are attached, form an 8, 9, or 10-membered carbocyclic or heterocyclic ring containing 8 to 10 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 each R 20 is independently selected from the group consisting of OH, SH, CN, NO 2 , halo, oxo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, —(C 1-4 alkyl)-(C 1-4 alkoxy), —(C 1-4 alkoxy)-(C 1-4 alkoxy), C 1-4 haloalkoxy, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, di(C 1-4 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-4 alkylaminocarbonylamino, and di(C 1-4 alkyl)aminocarbonylamino; and
wherein Ar is connected to the iodonium

Assignees

• Massachusetts Gen Hospital

Inventors

• Vasdev Neil
• Rotstein Benjamin H
• Liang Huan Steven

Classifications

• C07D319/08 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• C07D413/12

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

• C07D319/06

  not condensed with other rings · CPC title

• C07D405/12

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