{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T08:02:53Z","timestamp":1769328173671,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:p>(<jats:italic>R<\/jats:italic>)\u20102\u2010(4\u2010(Benzo[d]oxazol\u20102\u2010yl)piperazin\u20101\u2010yl)\u20104\u2010((tetrahydro\u20102<jats:italic>H<\/jats:italic>\u2010pyran\u20104\u2010yl)amino)\u20106,7\u2010dihydrothieno[3,2\u2010d]pyrimidine 5\u2010oxide (<jats:bold>1<\/jats:bold>) and (<jats:italic>R<\/jats:italic>)\u20102\u2010(4\u2010(4\u2010chlorophenoxy)piperidin\u20101\u2010yl)\u20104\u2010((tetrahydro\u20102<jats:italic>H<\/jats:italic>\u2010pyran\u20104\u2010yl)amino)\u20106,7\u2010dihydrothieno[3,2\u2010d]pyrimidine 5\u2010oxide (<jats:bold>2<\/jats:bold>) are two potent and selective inhibitors of phosphodiesterase type 4 (PDE4). In this manuscript, we report the detailed synthesis of these two compounds labeled with carbon 14 and with stable isotopes. The core (<jats:italic>R<\/jats:italic>)\u20104\u2010((tetrahydro\u20102<jats:italic>H<\/jats:italic>\u2010pyran\u20104\u2010yl)amino)\u20106,7\u2010dihydrothieno[3,2\u2010d]pyrimidine 5\u2010oxide is common in both inhibitors. In the radioactive synthesis, the carbon 14 atom was introduced in the benzoxazole moiety using [<jats:sup>14<\/jats:sup>C]carbon disulfide to obtain <jats:bold>[<\/jats:bold><jats:sup><jats:bold>14<\/jats:bold><\/jats:sup><jats:bold>C]\u20101<\/jats:bold> in five steps at a 55% overall yield. [<jats:sup>14<\/jats:sup>C]Urea was used to incorporate the carbon 14 atom in two steps in the dihydrothieno[3,2\u2010d]pyrimidine intermediate, which was then transformed in four more steps to <jats:bold>[<\/jats:bold><jats:sup><jats:bold>14<\/jats:bold><\/jats:sup><jats:bold>C]\u20102<\/jats:bold> at a 30% overall yield. Both compounds were isolated with specific activities higher than 54\u2009mCi\/mmol, radio\u2010 and chemical\u2010purities higher than 99%, and with excellent enantiomeric excess. In the stable isotope synthesis, [<jats:sup>2<\/jats:sup>H<jats:sub>8<\/jats:sub>]piperazine was used to prepare <jats:bold>[<\/jats:bold><jats:sup><jats:bold>2<\/jats:bold><\/jats:sup><jats:bold>H<\/jats:bold><jats:sub><jats:bold>8<\/jats:bold><\/jats:sub><jats:bold>]\u20101<\/jats:bold> in three steps in 72% overall yield, while [<jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>]phenol was used to prepare <jats:bold>[<\/jats:bold><jats:sup><jats:bold>13<\/jats:bold><\/jats:sup><jats:bold>C<\/jats:bold><jats:sub><jats:bold>6<\/jats:bold><\/jats:sub><jats:bold>]\u20102<\/jats:bold> in four steps in 18% overall yield.<\/jats:p>","DOI":"10.1002\/jlcr.4054","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T21:29:03Z","timestamp":1690234143000},"page":"353-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Carbon 14 and stable isotope synthesis of two potent and selective phosphodiesterase type 4 inhibitors"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0024-9792","authenticated-orcid":false,"given":"Bachir","family":"Latli","sequence":"first","affiliation":[{"name":"The Radiosynthesis Laboratory, Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc.  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