Strategy for ¹⁴C‐labeling of a series of bis(heteroaryl)piperazines

Abstract

Four bis(heteroaryl)piperazines labeled with carbon-14 in the 2-position of imidazole moiety were prepared as part of a 4-step (or 5-step) sequence from 5-hydroxymethyl-2-mercapto-1-benzylimida-zole-[2-14 C] as a key synthetic intermediate which has been synthesized from potassium [14 C]-thiocyanate.

Synthesis of a series of carbon-14 labeled tetrahydropyrido[4,3-d]pyrimidin-4(3H)-ones

“…18 Then 6-benzyl-2-phenyl-[2-14 C]-5,6,7,8-tetrahydro-pyrido [4,3-d]pyrimidin-4(3H)-one 13 was produced via the coupling of methyl 1-benzyl-4-oxopiperidine-3-carboxylate 12 with benz[amidino-14 C] amidine hydrochloride 1 in the presence of a solution of sodium ethoxide in dry ethanol in 62% yield. The latter product 13 could then be converted to 2-phenyl-[2-14 C] -5,6,7,8-tetrahydropyrido [4,3-d]pyrimidin-4(3H)-one 14 in quantitative yield by treatment with hydrogen gas in anhydrous ethanol in the presence of Pd/C 5% under reflux condition during 48 h. 19 In the final step, the coupling of 14 with acyl chloride 15a-d was carried out in the presence of triethylamine and DMAP in THF, and 6-acyl-2-phenyl- [2][3][4][5][6][7][8][9][10][11][12][13][14]…”

“…11 To further elucidate the mechanism of action and investigate the pharmacokinetics and drug metabolism of these compounds, the preparation of suitable metabolically stable carbon-14 labels were required. 12 In this paper, we present a convenient synthetic pathway for the synthesis of a series of tetrahydropyrido [4,3-…”

Synthesis of the olanzapine labeled by carbon‐14

“…Therefore to further elucidate the mechanism of action and to support ongoing metabolism studies, there arose a need for analogs of these compounds carbon‐14 labeled in a biologically stable site. In our previous papers, we reported a convenient method for carbon‐14 labeling of Clozapine and Loxapine. [ 11 C]Olanzapine was prepared from desmethyl‐Olanzapine with [ 11 C]CH 3 OTf through N‐[ 11 C]methylation previously .…”