Expeditious syntheses of stable and radioactive isotope‐labeled anticonvulsant agent,JNJ‐26990990, and its metabolites |
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Authors: | Ronghui Lin Larry E. Weaner David C. Hoerr Rhys Salter Yong Gong |
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Affiliation: | Janssen Research & Development LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, , Spring House, PA, 19477‐0776 USA |
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Abstract: | Syntheses of stable and radioactive isotope‐labeled anticonvulsant agent, JNJ‐26990990, that is, N‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide and its metabolites are described. [13C15N]Benzo[b]thiophene‐3‐carbonitrile was first prepared by coupling of 3‐bromo‐benzo[b]thiophene with [13C15N]‐copper cyanide. The resultant [13C15N]benzo[b]thiophene‐3‐carbonitrile was reduced with lithium aluminum deuteride to give [13CD215N]benzo[b]thiophen‐3‐yl‐methylamine; which was then coupled with sulfamide to afford [13CD215N]‐N‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide, the stable isotope‐labeled compound with four stable isotope atoms. Direct oxidation of [13CD215N]‐N‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide with hydrogen peroxide and peracetic acid gave the stable isotope‐labeled sulfoxide and sulfone metabolites. On the other hand, radioactive 14C‐labeled N‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide was prepared conveniently by sequential coupling of 3‐bromo‐benzo[b]thiophene with [14C]‐copper cyanide, reduction of the carbonitrile to carboxaldehyde, and reductive amination with sulfamide. |
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Keywords: | isotope label N‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide metabolite anticonvulsant agent |
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