Coo M

Scheme 22

Aldehydes 62 were reacted with an excess of either n-butyllithium or allylmagnesium chloride 63, giving the metal alkoxides 64, which were quenched with carboxylic acid func-tionalized resin. This resin also served a dual role in quenching excess of the organometallic reactant. Excess of carbonyl compound was quenched with primary amine-substituted resin and the products were obtained pure (>95 %). Other examples of the CMR/R strategy have also been published [43], and for the synthesis of heterocyclic carboxamides this strategy has been combined with the use of resin-bound reagents [44].

A combination of solid-phase extraction and liquid-phase extraction, as well as the use of solution scavengers, has been employed for the synthesis of thiazole libraries (Scheme 23) [45].

The synthesis is based on the Hantzsch condensation of thioureas 66 with 2-bromoketones 67 to give the 2-aminothiazoles 70. The excess of 67 was trapped with N-(4-carboxyphenyl)thiourea 68 and removed by SPE. Subsequent treatment of the aminothia-zoles 70 with a series of amino acid-derived isocyanates 71 gave the second generation of thi-azoles 74. Excess of 71 was quenched with 1,2-diaminoethane 72 and removed by SPE. Saponification gave the third generation of thiazole acids 75, which were transformed into the corresponding amides 77 by using EDC and amine 76. Again, all the excesses of reagents could be removed by SPE or LPE. Liquid-phase extractions were performed by the use of aqueous citric acid and all the solid-phase extractions were realized using neutral alumina [46],

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