Patent GB-1511571-A (GB)
Title: Lactam compounds and conjugates
IPC: A61K39/385
Filed: 1975-04-02
Abstract: 1511571 Lactam derivatives and intermediates therefor; spin-label compounds SYNTEX ENERGY RESEARCH Ine and VARIAN ENERGY [trading as SYVA CO] 2 April 1975 [28 June 1974] 13488/75 Heading C2C [Also in Divisions C3 and G1] (1.1) The reaction of chloroacetic acid/sodium bicarbonate and sodium diphenylhydantoin yields; 3- (N - carboxymethyl)diphenylhydantoin (1.2) The reaction of sodium diphenylhydantoin and chloroacetonitrile yields; 3-(N-cyanomethyl)- diphenylhydantoin which is hydrolysed with sodium ethoxide/ethanol to; 3 - (N - carboxymethyl)diphenylhydantoin (1.3) Sodium diphenylhydantoin is reacted with ethyl 2-bromopropionate to yield; 2-(N-diphenylhydantoinyl)- propionic acid, ethyl ester which is hydrolysed with aqueous sodium hydroxide to; 2-(N-diphenylhydantoinyl)propionic acid (1.4) Sodium diphenylhydantoin is reacted with ethyl n-5- bromopentanoate to yield; 5-(N<SP>31</SP>-diphenylhydantoinyl)pentanoic acid, ethyl ester which, on hydrolysis with aqueous hydroxide, yields 5 - (N<SP>31</SP> - diphenylhydantoinyl)pentanoic acid (1.5) Sodium diphenylhydantoin is reacted with 2 - chloroethoxyacetonitrile to yield; (2 - (N - diphenylhydantoinyl)ethoxy)acetonitrile which is hydrolysed with sodium hydroxide/ ethanol to; (2 - (N - diphenylhydantoinyl) - ethoxy)acetic acid. (1.6) 5-(p-hydroxyphenyl)- 5 - phenylhydantoin is reacted with sodium chloroacetate to yield; 5-(p-carboxymethoxyphenyl) - 5 - phenylhydantoin. (1.7) Primidone, reduced with sodium hydride, is reacted with ethyl bromoacetate to yield; 2-deoxo-1-barbiturylacetic acid, ethy elster which is hydrolysed with sodium hydroxide to yield; 2-deoxo-1- barbiturylacetic acid. (1.8) Phenyldiethyl malonate, reduced with sodium hydride and the product reacted with 6-bromo-1-hexene to yield; diethyl - 2 - phenyl - 2 - (5<SP>1 </SP>- hexenyl - 1<SP>1</SP>)- malonate which, on ozonolysis, yields; diethyl 2 - phenyl - 2 - (5<SP>1</SP>- pentanal - 1<SP>1</SP> - yl) - malonate which is treated with p-toluene sulphonic acid to yield; diethyl 2-phenyl-(5<SP>1</SP>-pentanal-1<SP>1</SP>-yl)- malonate diethyl acetal which is treated' with thiobarbituric acid, and the product hydrogenated over Raney nickel to yield; 2-deoxo-5- phenyl - 5 - (5<SP>1</SP> - pentanal -  1<SP>1</SP> - yl) - thiobarbituric acid diethyl acetal which is treated with acetic acid to yield; 2-deoxo-5-(5<SP>1</SP>-pentanal-1<SP>1</SP>-yl)barbituric acid which is oxidized with chromic acid/sulphuric acid to; 5-(2<SP>1</SP>-deoxo-5<SP>1</SP>-phenylbarbituryl)pentanoic acid. (1.9) Zerantin, reduced with sodium hydride, is reacted with iodoacetic acid to yield; 1-carboxymethylzarontin. (1.10) Ethyl cyanoacetate and ethyl levalinate are reacted to yield; diethyl 2-cyano-3- methylhex - 2 - en - 1,6 - dionate which is treated with potassium cyanide to yield 2-methyl-2- (21 - cyanomethoxyethyl) - 3 - cyanomethoxysuccinimide; which is treated with sodium hydroxide and phosphonic acid to yield 2- methyl - 2 - (2<SP>1</SP>- carbomethoxyethyl) - 3 - carbomethoxy succinimide which is treated with sodium hydroxide to yield 2-methyl-2-carboxyethyl-3- carboxysuccinimide which is refluxed with acetic acid to yield; 2-carboxyethyl-2-methylsuccinimide. Spin-label compounds were obtained by the reaction of, in triethylamine, 2,2,5,5-tetramethyl - 3 - amino - 1 - oxylpyrrolidine and (4.1) methyl (N<SP>3</SP>-diphenyl hydantoinyl)acetamidate; (4.2) 5-(p-carboxymethoxy phenyl)-5- phenylhydantoin; (4.3) 2-carboxyethyl-2-methylsuccinimide.