{"created":"2023-05-15T14:56:03.450612+00:00","id":76130,"links":{},"metadata":{"_buckets":{"deposit":"f11c77ca-a9d2-4feb-97be-ba940c9e5065"},"_deposit":{"created_by":1,"id":"76130","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"76130"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00076130","sets":["10:28"]},"author_link":["765018","765016","765017","765020","765023","765025","765021","765024","765019","765022"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2019-05-30","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: [18F]Fluoroalkylation is a useful method for introduction of fluorine-18 into molecules containing NH, OH, and SH-groups. Using various [18F]fluoroalkylating agents, we are routinely producing clinically-useful 18F-radiotracers, such as [18F]FMeNER-d2, [18F]FEDAA1106, [18F]FEDAC, [18F]FE-SPARQ and [18F]FEtPE2I. Recently, we have reported a convenient [18F]fluoroalkylation route for introducing 3-[18F]fluoro-2-hydroxypropyl ([18F]FHP) group into a targeted molecule via ring-opening reaction of [18F]epifluorohydrin ([18F]2) with phenol analogs by using an automated synthesis system [1]. However, despite the usefulness of epifluorohydrin in organic chemistry, the reaction of [18F]2 with low nucleophilic reagents, such as aromatic amine has rarely been reported. To extend application of this technique, in this study, we developed a simple method for introducing [18F]FHP group into aryl or heteroaryl amines in the presence of Sc(OTf)3. \nMethods: Unlabeled 3a-n were prepared by reactions of aryl or heteroaryl amines with epifluorohydrin in the presence of Sc(OTf)3 at moderate chemical yields (40-84%). [18F]2 was synthesized by the reaction of glycidyl tosylate 1 (10 mg) and [18F]KF/K2.2.2 in 1,2-dichlorobenzene at 130 oC for 2 min and immediately transferred by distillation into a reaction vial including aromatic amine in CCl4. The reaction conditions for the N-[18F]fluoroalkylation of p-anisidine as a model compound with [18F]2 were optimized with regard to solvents, temperatures and times. Under the optimized conditions, [18F]3a-n were synthesized by the reaction of various aryl or heteroaryl amines and [18F]2. Radiochemical conversions (RCCs) were determined by radio-HPLC for these reaction mixtures.\n \nFigure 1. Synthesis of [18F]3a–n\n\nResults: Firstly, a suitable solvent for N-[18F]fluoroalkylation of p-anisidine with [18F]2 in the presence of Sc(OTf)3 (10 mol%) was examined. In coordinating solvents such as THF and DMF, the reaction did not effectively proceed. On the other hand, the reaction efficiency was significantly increased by the use of nonpolar solvent such as CCl4. Under several temperatures and times investigated, the reaction performed in CCl4 at 50 oC for 20 min was found to give the best [18F]fluoroalkylating result. According to the optimized conditions, [18F]3a was synthesized by reaction of p-anisidine and [18F]2 using an automated synthesis system. By purification for the reaction mixture with semi-preparative HPLC and formulation, [18F]3a was obtained with a synthesis time of 85 ± 3 min and 27% radiochemical yield (isolated-yield based on the cyclotron-produced [18F]F-). To demonstrate suitability of this method, [18F]3b-n were synthesized from various aryl or heteroaryl amines containing halogen, alkyl, acetyl or hydroxyl groups. Radio-HPLC analyses for the reaction mixtures indicated that [18F]3b-l and [18F]3m-n were yielded in 25–69% and 6–16% RCCs, respectively. Using 2,2,2-trifluoroethanol (TFE) as a co-solvent, N-[18F]fluoroalkylation of aryl amines proceeded more effectively to give the corresponding product [18F]3b-l in  30–98% RCCs.\nConclusion: Scandium-catalyzed N-[18F]fluoroalkylation with [18F]2 allowed facile introduction of [18F]FHP group into aryl or heteroaryl amines under mild conditions. Next, we will focus on improving efficiency for the N-[18F]fluoroalkylation of heteroaryl amines.\n\nReferences: [1] M. Fujinaga, T. Ohkubo, T. Yamasaki, et al. ChemMedChem. 2018, 13, 1723–1731.\n","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"ISRS2019","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"765016","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ohkubo, Takayuki"}],"nameIdentifiers":[{"nameIdentifier":"765017","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kumata, Katsushi"}],"nameIdentifiers":[{"nameIdentifier":"765018","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"765019","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang"}],"nameIdentifiers":[{"nameIdentifier":"765020","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"765021","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ohkubo, Takayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"765022","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kumata, Katsushi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"765023","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"765024","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"765025","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Development of scandium-catalyzed N-[18F]fluoroalkylation of aryl and heteroaryl amines with [18F]epifluorohydrin.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Development of scandium-catalyzed N-[18F]fluoroalkylation of aryl and heteroaryl amines with [18F]epifluorohydrin."}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-06-03"},"publish_date":"2019-06-03","publish_status":"0","recid":"76130","relation_version_is_last":true,"title":["Development of scandium-catalyzed N-[18F]fluoroalkylation of aryl and heteroaryl amines with [18F]epifluorohydrin."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:37:10.665888+00:00"}