title: Expeditious syntheses of stable and radioactive isotope-labeled anticonvulsant agent, JNJ-26990990, and its metabolites.
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. [(13)C(15)N]Benzo[b]thiophene-3-carbonitrile was first prepared by coupling of 3-bromo-benzo[b]thiophene with [(13)C(15)N]-copper cyanide. The resultant [(13)C(15)N]benzo[b]thiophene-3-carbonitrile was reduced with lithium aluminum deuteride to give [(13)CD2(15)N]benzo[b]thiophen-3-yl-methylamine; which was then coupled with sulfamide to afford [(13)CD2(15)N]-N-(benzo[b]thien-3-ylmethyl)-sulfamide, the stable isotope-labeled compound with four stable isotope atoms. Direct oxidation of [(13)CD2(15)N]-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 (14)C-labeled N-(benzo[b]thien-3-ylmethyl)-sulfamide was prepared conveniently by sequential coupling of 3-bromo-benzo[b]thiophene with [(14)C]-copper cyanide, reduction of the carbonitrile to carboxaldehyde, and reductive amination with sulfamide.
authors.affiliation: Janssen Research & Development LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Welsh & McKean Road, Spring House, PA, 19477-0776, USA.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Lin
authors.forename: Larry E
authors.initials: LE
authors.lastname: Weaner
authors.forename: David C
authors.initials: DC
authors.lastname: Hoerr
authors.forename: Rhys
authors.initials: R
authors.lastname: Salter
authors.forename: Yong
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis*; D002247:Carbon Isotopes / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D003903:Deuterium / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D009587:Nitrogen Isotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis*; D013876:Thiophenes / Q000138:chemical synthesis*
chemical_list: D000927:Anticonvulsants; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D009587:Nitrogen Isotopes; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D013876:Thiophenes; D003903:Deuterium; C545991:N-((benzo(b)thien-3-yl)methyl)sulfamide
keywords: N-(benzo[b]thien-3-ylmethyl)-sulfamide; anticonvulsant agent; isotope label; metabolite