Efficient solid-phase synthesis of 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones.
The solid-phase synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones from MBHA and Wang resin is described. Reaction of resin-bound amino acids with isocyanates yield resin-bound ureas, which further react with chlorocarbonyl isocyanate in toluene at 65 degrees C to selectively afford the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones. Selective alkylation at the N-5 position of the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones was accomplished by treatment with alkyl halides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The desired products were cleaved from their solid support and obtained in good yield and purity. The method can be employed in production of toltrazuril analogue libraries for identification of new anticoccidial agents.
Yu
Yongping
Y
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Ostresh
John M
JM
Houghten
Richard A
RA
D000478:Alkylation; D002853:Chromatography, Liquid; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry
D014227:Triazines