合成路线:The synthesis of [14C]- and deuterium-labeled bisaramil hydrochloride has been reported:1) The reduction of (14)CO2 with LiAlH4 in THF gives labeled formaldehyde (II),which by a Mannich reaction is condensed with ethylamine (IV) and N-methylpiperidin-4-one (III) by means of acetic acid in refluxing methanol to yield labeled 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one (V).The reduction of (V) with NaBH4 in methanol/NaOH affords a mixture of the alpha- and beta-isomers of the labeled 9-hydroxy derivative (VI + VII).After separation by its different solubility in isopropanol,the alpha-isomer is condensed with 4-chlorobenzoyl chloride (VIII) in hot pyridine to give [2,4-14C]-labeled bisaramil.
合成路线:2) Hexadeuteroethyl alcohol (IX) is treated with red phosphorus and I2 at reflux temperature to give pentadeuteroethyl iodide (X),which is condensed with potassium phthalimide (XI) in DMF,yielding N-(pentadeuteroethyl)phthalimide (XII).The hydrolysis of (XII) with hydrazine and HCl affords pentadeuteroethylamine (XIII),which is condensed with 1-methylpiperidin-4-one (III) and formaldehyde (XIV) in a Mannich reaction to give 3-methyl-7-(pentadeuteroethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (XV).The reduction of (XV) with NaBH4 as before yields the diastereomeric mixture (XVI + XVII).Finally,the alpha-isomer (XVI) is condensed with 4-chlorobenzoyl chloride (VIII) as before to give the pentadeuterium-labeled bisaramil.
参考文献标题:Synthesis of bisaramil labelled with carbon-14 and deuterium
文献作者:Mlinko,S.; Simon Trompler,E.; Szammer,J.
参考来源:J Label Compd Radiopharm 1994,34(4),313
产品链接: CAS No. 96480-44-3›› 产品链接: CAS No.89194-77-4››