ONE POT SYNTHESIS OF 18F LABELEDTRIFLUOROMETHYLATED COMPOUNDS WITH DIFLUORO(IODO)METHANE

摘要

The present invention relates to compositions and methods for the synthesis of 18F labeled compounds. In particular, the present invention relates to a copper (I) mediated one pot method for 18F-trifluoromethylation of aromatic- or heteroaromatic halides with difluoro(iodo)methane (e.g., for use at PET imaging agents).

主权项

1. A method of synthesizing a compound of the formula (I) or (II) or (III), wherein Y═N, CH, or CR; wherein Z═NR, O, or S; and wherein R is one or more than one and dependent or independent of each other and selected from the group consisting of substituted, non-substituted, functionalized, non-functionalized H, halogen, nitro, nitril, isonitril, cyanate, isocyanate, hydroxyl, amide, alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkyl-, aryl-, heteroaryl ether, alkyl-, aryl-, heteroaryl thioether, alkyl-, aryl-, heteroaryl ketone, alkyl-, aryl-, heteroaryl thioketone, alkyl-, aryl-, heteroaryl amide, alkyl-, aryl-, heteroaryl thioamide, alkyl-, aryl-, heteroaryl urea, alkyl-, aryl-, heteroaryl thiourea, alkyl-, aryl-, heteroaryl urethane, alkyl-, aryl-, heteroaryl thiourethane, alkyl-, aryl-, heteroaryl ester, alkyl-, aryl-, heteroaryl thioester, alkyl-, aryl-, heteroaryl amine, monocyclic, and multi cyclic, isotope containing and wherein n=1-4, comprising: contacting base, 18F− ion and a copper source, and a compound of the formula (IV) or (V) or (VI) wherein Y═N, CH, or CR and wherein Z═NR, O, or S and wherein X═Cl, Br, or I and wherein R is one or more than one and dependent or independent of each other and selected from substituted, non-substituted, functionalized, non-functionalized H, halogen, nitro, nitril, isonitril, cyanate, isocyanate, hydroxyl, amide, alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkyl-, aryl-, heteroaryl ether, alkyl-, aryl-, heteroaryl thioether, alkyl-, aryl-, heteroaryl ketone, alkyl-, aryl-, heteroaryl thioketone, alkyl-, aryl-, heteroaryl amide, alkyl-, aryl-, heteroaryl thioamide, alkyl-, aryl-, heteroaryl urea, alkyl-, aryl-, heteroaryl thiourea, alkyl-, aryl-, heteroaryl urethane, alkyl-, aryl-, heteroaryl thiourethane, alkyl-, aryl-, heteroaryl ester, alkyl-, aryl-, heteroaryl thioester, alkyl-, aryl-, heteroaryl amine, monocyclic, and multi cyclic, isotope containing and wherein n=1-4, and a ligand and difluoro(iodo)methane, in a solvent a single reaction vessel; and incubating for an appropriate incubation time at an elevated temperature.