Solution-phase synthesis reaction conditions

Since 1986, when the very first reports on the use of microwave heating to chemical transformations appeared [147,148], microwave-assisted synthesis has been shown to accelerate most solution-phase chemical reactions [24-27,32,35]. The first application of microwave irradiation for the acceleration of reaction rate of a substrate attached to a solid support (SPPS) was performed in 1992 [36]. Despite the promising results, microwave-assisted soHd-phase synthesis was not pursued following its initial appearance, most probably as a result of the lack of suitable instriunentation. Reproducing reaction conditions was nearly impossible because of the differences between domestic microwave ovens and the difficulties associated with temperature measurement. The technique became a Sleeping Beauty interest awoke almost a decade later with the publication of several microwave-assisted SPOS protocols [37,38,73,139,144]. There has been an extensive... 

Furthermore, the polymeric carrier must be robust enough to withstand the reaction conditions used in solution-phase synthesis. Consequently, most soluble... 

The high yields obtained by using similar reaction conditions to the solution-phase synthesis did not require major efforts to optimize the reaction conditions. The minor adjustments have already been described above. 

A three-component solution phase synthesis of substituted sulfonamides by reaction of an acrylic ester, an aldehyde and toluenesulfonamide under MBH reaction conditions has been reported. The reaction is catalyzed by... 

Resin 23 was first swollen in CH2CI2 and, in a manner that parallels the route employed in the solution-phase synthesis, was reacted with a selected benzylsulfonyl chloride and t-BuOLi as a base to afford the corresponding sulfonamide resin 28, containing the first diversity element R. The sulfonamide resin 28 was then reacted under Mitsunobu conditions (PPha (triphenyl phosphine), DIAD (diisopropyl azodicarboxylate), THE, room temperature) with the appropriate alcohols. This process efficiently produced resin 29 and introduced the second diversity element R. Cyclization reaction of resin 29 was promoted by sodium hydride in DMF and led to the formation of the desired thiazolo[4,5-c] [l,2]thiazine resin 30. Treatment of resin 30 with mCPBA in CH2CI2 generated the resin-bound cyclic sulfonamide 31. Finally, the thiazolo[4,5-c][l,2]thiazine derivatives 5 were formed and cleaved from the resin (in a traceless manner" ) by treatment of resin 31 with the corresponding amines (R R" N diversity elements) in respectable yields (34 examples, from 11% to 29% for seven linear steps starting with Merrifield resin 1, Table 10.4). 

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