Piperazines polymer bound

Quinazolines are of great interest in the pharmaceutical industry as protein tyrosine kinase inhibitors. Dener et al 8 described a synthesis starting from 2-methoxybenzaldehyde, Wang, or Rink resins. With the aldehyde resin reductive aminations were undertaken to yield polymer-bound secondary amines (Fig. 7). The latter were subjected to 2,4-dichloro-6,7-dimethoxyquinazoline to give the 4-amino-substituted derivatives. These were then allowed to react with primary or secondary amines at 135-140° in the presence of DBU in DMA. As a result of a detailed scope and limitation study, Dener et al,28 note that some bifunctional amines, such as piperazine, give to some extent dimeric derivatives. 

Polymer-bound piperazine can also be used for the deprotection of phosphane-, phosphate- and phosphinite-borane complexes to give the corresponding free... 

Scheme 6.1 A polymer-bound piperazine for Fmoc-deprotection.

Carpino et presented polymer-bound piperazines 33 which caused deblocking of Fmoc... 

Fig. 16. Sdiematk presentation of peptide synthesis by inverse solid phase method based DO the use of polymer-bound amino acid active esters (coupling reagent) and polymer-bound piperazine (deprotecting reagent)...

Release of compounds from polymer-bound carbamates has not to be performed via nucleophilic attack but can also be induced by the addition of acids like, for example, TFA in various concentrations. The released target compounds are either primary or secondary amines. The synthesis described in Scheme 34 has been recently published by DoUe et al. [183]. Synthesis of piperazines 227 has been conducted on a or-methylbenzyl resin 223 that has been activated with 4-NPCF and that has been fmther reacted with diethanolamine 224. After mesylation of the two resulting terminal hydroxy groups, reaction with a primary amine 226 and base gave immobilized piper-... 

The first example of iron-activated nucleophilic aromatic substitution on solid phase has been presented by Ruhland et al. [141], who attached [(cyclopentadienyl)-benzene Fe(II)] PF6 to polymer-bound piperazine (Scheme 55). The complex 68 was subjected to a variety of nucleophiles using different protocols. The decomplexation was achieved by irradiation in the presence of phenanthroline, and in the final step the resin-bound products were cleaved with methyl chloroformate to give corresponding carbamates in good yields. 

Dry the resulting polymer in vacuo to yield PEG-bound piperazine 3a quantitatively. Transfer the derivatized polymer 3 (510 mg) to another 30 mL round bottom flask equipped with a magnetic stirrer bar and nitrogen inlet rubber septum. 

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