1) By condensation of 2-nitroimidazole (I) with 3-(1-piperidino)propyliene oxide (II) in refluxing ethanol.
Hexamethylenebisacetamide is prepared by reacting 1,6-hexanediamine (I) with two moles of acetic acid.
2) By condensation of 1-(3-chloro 2 hydroxypropyl)-2-nitroimidazole (III) with piperidine (IV) in refluxing methanol.
3) By condensation of 1-(2,3-epoxypropyl)-2 nitroimidazole (V) with (IV) in refluxing ethanol.
1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin], with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C. d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.
[2H]-Labeled RSU-1069 is synthesized as follows: The condensation of 2-nitroimidazole (I) with 3-chloro-1,2-epoxypropane (II) gives 1-(3-chloro-2-hydroxypropyl)-2-nitroimidazole (III), which is oxidized with CrO3 - H2SO4 in acetone yielding 1-(3-chloro-2-oxopropyl)-2-nitroimidazole (IV). The reduction of (IV) with NaB[2H]4 in ethanol affords 1-(3-chloro-2-hydroxy-2(2H)-propyl)-2-nitroimidazole (V), which is cyclized with NaOH to the corresponding labeled epoxide (VI). Finally, this compound is condensed with aziridine (VII) by means of triethylamine in refluxing ethanol.
[2H]-Labeled pimonidazole is synthesized as follows: The condensation of 2-nitroimidazole (I) with 3-chloro-1,2-epoxypropane (II) gives 1-(3-chloro-2-hydroxypropyl)-2-nitroimidazole (III), which is oxidized with CrO3 - H2SO4 in acetone yielding 1-(3-chloro-2-oxopropyl)-2-nitroimidazole (IV). The reduction of (IV) with NaB[2H]4 in ethanol affords 1-(3-chloro-2-hydroxy-2(2H)-propyl)-2-nitroimidazole (V), which is cyclized with NaOH to the corresponding labeled epoxide (VI). Finally, this compound is condensed with piperidine (VII) in refluxing ethanol.