METHOD FOR PRODUCTION OF F-18 LABELED AMYLOID BETA LIGANDS
This invention relates to methods, which provide access to [F-18]fluoropegylated (aryl/heteroaryl vinyl)-phenyl methyl amine derivatives.
1 . A Method for producing a compound of Formula I
comprising the steps of:
Step 1: Radiolabeling compound of Formula II with a F-18 fluorinating agent, to obtain compound of Formula I, if R═H or to obtain compound of Formula III, if R═PG
Step 2: If R═PG, cleavage of the protecting group PG to obtain a compound of Formula I
Step 3: Purification and Formulation of a compound of Formula I
wherein:
n=1-6,
X is selected from the group consisting of
a) CH,
b) N,
R is selected from the group consisting of
a) H,
b) PG,
PG is an “Amine-protecting group”,
LG is a leaving group,
wherein in step 3 a HPLC method is used, wherein the HPLC solvent or solvent mixture is part of an injectable Formulation of compound I suitable for injection into humans.
2 . A method according to claim 1 , wherein PG is selected from the group consisting of:
a) Boc,
b) Trityl and
c) 4-Methoxytrityl.
3 . A method according to claim 1 , wherein LG is selected from the group consisting of:
a) Halogen and
b) Sulfonyloxy,
Halogen is chloro, bromo or iodo.
4 . A method according to claim 3 , wherein Sulfonyloxy is selected from the group comprising:
a) Methanesulfonyloxy,
b) p-Toluenesulfonyloxy,
c) (4-Nitrophenyl)sulfonyloxy,
d) (4-Bromophenyl)sulfonyloxy.
5 . A method according to claim 1 , wherein n=3 and X═CH.
6 . A method according to claim 1 , wherein n=3, X═CH, R=Boc, and LG=Methanesulfonyloxy.
7 . A method according to claim 1 , wherein the HPLC solvent is selected from the group consisting of ethanol, an aqueous buffer or an ethanol/aqueous buffer mixture.
8 . A method according to claim 7 , wherein the aqueous buffer is selected from the group of solutions of sodium chloride, sodium phosphate buffer, ascorbic acid, ascorbate buffer, or mixtures thereof.
9 . A method according to claim 1 , wherein 10-50 μmol of a compound of Formula II is used.
10 . A method according to claim 1 , wherein the method is performed as a fully automated process.
11 . A kit, comprising a sealed vial containing a compound of Formula II and a sealed vial containing a solution for HPLC that can be part of an injectable Formulation of compound I suitable for injection into humans.
12 . A kit according to claim 10 , wherein the solution for HPLC that can be part of an injectable Formulation of compound I suitable for injection into humans is selected from the group consisting of ethanol, an aqueous buffer or an ethanol/aqueous buffer mixture.
13 . A kit according to claim 12 , wherein the aqueous buffer is selected from the group consisting of sodium chloride, sodium phosphate buffer, ascorbic acid, ascorbate buffer, or mixtures thereof.