Synthesis of 2-Amino-4-pyrimidinones from Resin-Bound Guanidines Prepared Using Bis(allyloxycarbonyl)-Protected Triflylguanidine

Abstract

We have synthesized novel heterocyclic compounds from resin-bound guanidines. For this purpose, an amine immobilized on a solid support was acylated with protected amino acids. Following the deprotection, the liberated amines were guanidinylated utilizing a new member of the family of diurethane-protected triflyl guanidine reagents, N,N'-bis(allyloxycarbonyl)-N' '-triflylguanidine. The deprotected guanidines were subsequently regioselectively cyclized with beta-keto esters yielding novel compounds containing heterocyclic structures in high purities.

Trifluoromethanesulfonamides and Related Compounds

“…N -Triflylguanidines and their perfluoroalkanesulfonyl analogues (R 2 N) 2 CNSO 2 R F are interesting from the synthetical point of view because they are efficient reagents for the guanidinylation of amines and from the structural point of view as push–pull imines. First N -triflylguanidines with protecting groups at the amine nitrogen atoms were synthesized from the properly diprotected guanidines and triflic anhydride. − Different N -triflylguanidines were synthesized by Yagupol’skii and co-workers using substrates that already contained the CF 3 SO 2 N moiety. ,,, A one-pot method for preparation of trisubstituted N -triflylguanidines was suggested by the reaction of aryl isothiocyanates with triflamide followed by treatment with secondary amines . The tetrasubstituted derivatives were obtained by alkylation of the remaining NH group. Most recently, we have proposed two new approaches to the synthesis of N -triflylguanidines in practically quantitative yield from the reaction of N -sulfinyltriflamide ureas and by addition of triflamide to carbodiimides. , …”

Synthesis of Deuterium‐Labelled 3‐Hydroxy‐L‐arginine: Comparative Studies on Different Protecting‐Group Strategies

“…Deuterated alcohols ( R )‐ 14b , ( S )‐ 14b , and ( R )‐ 14c were then converted with tris‐Cbz‐guanidine 15 using Goodman's guanidinylation method under Mitsunobu conditions27 to give protected guanidines ( R )‐ 17b , ( S )‐ 17b , and ( R )‐ 17c , respectively, in yields of 74–81 %. Using tris‐Alloc‐guanidine 16 28 instead of tris‐Cbz‐guanidine 15 under analogous conditions, TBDPS‐ and Alloc‐protected derivative 17d was obtained in 90 % yield (Scheme ).…”

Backbone Amide Linker in Solid-Phase Synthesis

“…Zapf and Goodman used 2,6-dimethoxy-4-hydroxybenzaldehyde coupled to bromoalkyl-derivatized Tentagel resin to prepare 2-amino-4-pyrimidinones from guanidines (19). 140 RA with benzylamine was followed by acylation with Fmocprotected amino acids. After deprotection, the amine was guanidinylated, and subsequent reaction with β-keto esters yielded the desired heterocyclic structures in good purities (see Chart 9).…”

“…Zapf and Goodman used 2,6-dimethoxy-4-hydroxybenzaldehyde coupled to bromoalkyl-derivatized Tentagel resin to prepare 2-amino-4-pyrimidinones from guanidines ( 19 ) . RA with benzylamine was followed by acylation with Fmoc-protected amino acids.…”