4-(diethylamino)-4-oxobutanoic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.46 g. N,N-Diethylsuccinic acid monoamide and 4.3 g. dicyclohexylcarbodiimide are dissolved in 35 ml. tetrahydrofuran and 1.36 g. 2-cyanoaziridine is added to the resultant suspension. After subsequently stirring for 2 hours in an ice bath and leaving to stand overnight at ambient temperature, the dicyclohexylurea is separated off and the filtrate evaporated. There are thus obtained 2.9 g. 1-(N,N-diethylsuccinamoyl)-2-cyanoaziridine in the form of an oil. leaving to stand overnight at ambient temperature the dicyclohexylurea is separated off the filtrate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and 4-(diethylamino)-4-oxobutanoic acid to yield (3aR,4S,7aR)-methyl 4-(4-(diethylamino)-4-oxobutanoyloxy)-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate. MS [M+H]=296 (ester elimination ion); RT=1.22 min; UPLC Method I

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: using 3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione and 3-(diethylcarbamoyl)-propionic acid with N,N'-dicyclohexylcarbodiimide and 4-pyrrolidino-pyridine as the catalyst in methylene chloride there is obtained 2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorophenyl 3-(diethylcarbamoyl)propionate, m.p. 91°-93° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction of 3-(N,N-diethylcarbamoyl)propionic acid and diphenylphosphoryl azide in a solution of triethylamine and benzene provided a solution comprising 2-(N',N'-diethylcarbamoyl)ethyl isocyanate (I.R.: 2290 cm-1), which was reacted with 5-fluorouracil to provide 1-[N-[2-(N',N'-diethylcarbamoyl)ethyl]carbamoyl]-5-fluorouracil substantially in the similar method to that of Example 4.