Fluorination method

Patent metadata

Field	Value
Publication number	US-10287220-B2
Application number	US-201515127599-A
Country	US
Kind code	B2
Filing date	Mar 20, 2015
Priority date	Mar 20, 2014
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention relates to a process for producing an organic compound comprising an 18 F atom. The compounds comprising an 18 F can be useful as PET ligands for use in diagnostics and/or scanning. The process of the invention comprises treating an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp 2 hybridized carbon atom, with (i) 18 F— and (ii) a copper compound. The invention also provides the use of an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp 2 hybridized carbon atom, in a process for producing an organic compound comprising an 18 F atom, which process comprises treating the organoboron compound with (i) 18 F— and (ii) a copper compound. The invention also provides a compound of formula (XXXVII): wherein: each PG A is independently H or an alcohol protecting group; PG B is H or a carboxylic acid protecting group; each PG C is independently an amine protecting group; Z is a group selected from a boronic ester group, a boronic acid group, a borate group, and a trifluoroborate group; and a is an integer from 0 to 4.

First claim

The invention claimed is:

1. A process for producing an organic compound comprising an 18F atom, which process comprises treating an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridised carbon atom, with
(i) 18F − ; and
(ii) (a) a copper (II) salt of formula [L n Cu(OTf) 2 ] or (b) a copper (II) salt of formula Cu(OTf) 2 and L,
wherein:
n is an integer from 1 to 4; and
each L is the same or different and is a ligand selected from the group consisting of:
pyridine; pyridine substituted with one or more groups selected from C 1-6 alkyl and phenyl; quinoline; quinoline substituted with one or more groups selected from C 1-6 alkyl and phenyl; isoquinolone; isoquinoline substituted with one or more groups selected from C 1-6 alkyl and phenyl; pyrrole; pyrrole substituted with one or more groups selected from C 1-6 alkyl and phenyl; 2,3-benzopyrrole; 2,3-benzopyrrole substituted with one or more groups selected from C 1-6 alkyl and phenyl; N—C 1-6 alkylpyrazole; N—C 1-6 alkylpyrazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; N—C 1-6 alkyl-1,2-benzopyrazole; N—C 1-6 alkyl-1,2-benzopyrazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; N—C 1-6 alkyl-imidazole; N—C 1-6 alkyl-imidazole substituted with one or more groups selected from C 1-6 alkoxycarbonyl, C 1-6 alkyl and phenyl; pyridazine; pyridazine substituted with one or more groups selected from C 1-6 alkyl and phenyl; pyrimidine; pyrimidine substituted with one or more groups selected from C 1-6 alkyl and phenyl; benzopyrimidine; benzopyrimidine substituted with one or more groups selected from C 1-6 alkyl and phenyl; pyrazine; pyrazine substituted with one or more groups selected from C 1-6 alkyl and phenyl; benzopyrazine; benzopyrazine substituted with one or more groups selected from C 1-6 alkyl and phenyl; imidazo(1,2-b)pyridazine; imidazo(1,2-b)pyridazine substituted with one or more groups selected from C 1-6 alkoxy, C 1-6 alkyl and phenyl; [1,2,4]triazolo[1,5-a]pyridine; [1,2,4]triazolo[1,5-a]pyridine substituted with one or more groups selected from C 1-6 alkyl and phenyl; pyrazolo[1,5-a]pyridine; pyrazolo[1,5-a]pyridine substituted with one or more groups selected from C 1-6 alkyl and phenyl; 1H-pyrrolo[3,2-b]pyridine; 1H-pyrrolo[3,2-b]pyridine substituted with one or more groups selected from C 1-6 alkyl and phenyl; 1-C 1-6 alkyl-pyrrolo[2,3-b]pyridine; 1-C 1-6 alkyl-pyrrolo[2,3-b]pyridine substituted with one or more groups selected from C 1-6 alkyl and phenyl; 1-C 1-6 alkyl-1,2,3-triazole; 1-C 1-6 alkyl-1,2,3-triazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; 1-C 1-6 alkyl-benzo[d][1,2,3]triazole; 1-C 1-6 alkyl-benzo[d][1,2,3]triazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; 1-C 1-6 alkyl-1,2,4-triazole; 1-C 1-6 alkyl-1,2,4-triazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; oxazole; oxazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; benzoxazole; benzoxazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; isoxazole; isoxazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; benzisoxazole; benzisoxazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; thiazole; thiazole substituted with one or more groups selected from C 1-6 alkyl and phenyl; benzothiazole; and benzothiazole substituted with one or more groups selected from C 1-6 alkyl and phenyl.

2. A process according to claim 1 , wherein the organoboron compound comprises a boronic ester group, a boronic acid group, a borate group or a trifluoroborate group.

3. A process according to claim 1 , wherein the copper compound is a compound of formula [(Pyr) 4 Cu II (OTf) 2 ].

4. A process according to claim 1 wherein the organoboron compound is a compound of formula (II) or (III):

wherein:
Ar is an aryl ring or a heteroaryl ring;

each R A group is the same or different and is a group selected from substituted or unsubstituted C 1-20 alkyl, substituted or unsubstituted C 2-20 alkenyl, substituted or unsubstituted C 2-20 alkynyl, substituted or unsubstituted C 3-20 cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, cyano, amino, C 1-10 alkylamino, di(C 1-10 )alkylamino, arylamino, diarylamino, arylalkylamino, amido, acylamido, hydroxy, halo, carboxy, ester, acyl, acyloxy, C 1-20 alkoxy, aryloxy, haloalkyl, sulfonic acid, thiol, C 1-10 alkylthio, arylthio, sulfonyl, phosphoric acid, phosphate ester, phosphonic acid and phosphonate ester, wherein two or more R A groups may be bonded together to form one or more rings;
R B , R C , and R D are each independently selected from H, substituted or unsubstituted C 1-20 alkyl, substituted or unsubstituted C 2-20 alkenyl, substituted or unsubstituted C 2-20 alkynyl, substituted or unsubstituted C 3-20 cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, cyano, amino, C 1-10 alkylamino, di(C 1-10 )alkylamino, arylamino, diarylamino, arylalkylamino, amido, acylamido, hydroxy, halo, carboxy, ester, acyl, acyloxy, C 1-20 alkoxy, aryloxy, haloalkyl, sulfonic acid, thiol, C 1-10 alkylthio, arylthio, sulfonyl, phosphoric acid, phosphate ester, phosphonic acid and phosphonate ester, wherein two or more of R B , R C , and R D may be bonded together to form one or more rings;
Z is group selected from a boronic ester group, a boronic acid group, a borate group or a trifluoroborate group; and
x is an integer from 0 to 5.

5. A process according to claim 4 , wherein Z is a group of formula (IV):

wherein:
each Q is the same or different and is a group selected from —OR E , —OH, and fluoride;
each R E is the same or different and is a group selected from substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 3-10 cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acyl, ester, amido, and haloalkyl, wherein two or more R E groups may be bonded together to form one or more rings; and
y is 2 or 3.

6. A process according to claim 5 , wherein Z is a group of formula —B(OR E ) 2 .

7. A process according to claim 4 , wherein Z is a group of formula (V):

wherein alk 1 is a substituted or unsubstituted alkylene group, optionally interrupted with one or more —O— or —N(R F )— groups, wherein R F is a group selected from H, substituted or unsubstituted C 1-10 alkyl, acyl, ester, amido and acyloxy.

8. A process according to claim 4 , wherein Z is a group of formula (VI) or (VII):

wherein:
each R Fa is a group independently selected from substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 3-10 cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted het

Assignees

• Univ Oxford Innovation Ltd

Inventors

• Gouverneur Veronique
• Tredwell Matthew
• Preshlock Sean

Classifications

• C07B59/00 Primary

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• C07C67/317

  by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups · CPC title

• C07C209/74

  by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation · CPC title

• C07C303/40

  by reactions not involving the formation of sulfonamide groups · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title