“…[ 16,17] The N À O bond and the C 8 F 17 tag in 1 are separated by three methylene groups to mitigate the electron-withdrawing effect from the fluorine atoms. We speculated that this tert-butyl-N-perfluoroalkoxycarbamate would serve as a convenient surrogate for ammonia in the synthesis of Nmonoalkylated amides, ureas, and sulfonamides.…”
A novel fluorous-tagged ammonia equivalent has been developed. It is based on a nitrogen-oxygen bond, which can be cleaved in a traceless manner by a molybdenum complex or samarium diiodide. The application in the synthesis of ureas, amides, sulfonamides, and carbamates is described. The scope of the fluorous N-O linker is exemplified by the synthesis of itopride, a drug used for the treatment of functional dyspepsia. Itopride was synthesized with the aid of fluorous purification methods and the product was isolated in good overall yield, with high purity.
“…[ 16,17] The N À O bond and the C 8 F 17 tag in 1 are separated by three methylene groups to mitigate the electron-withdrawing effect from the fluorine atoms. We speculated that this tert-butyl-N-perfluoroalkoxycarbamate would serve as a convenient surrogate for ammonia in the synthesis of Nmonoalkylated amides, ureas, and sulfonamides.…”
A novel fluorous-tagged ammonia equivalent has been developed. It is based on a nitrogen-oxygen bond, which can be cleaved in a traceless manner by a molybdenum complex or samarium diiodide. The application in the synthesis of ureas, amides, sulfonamides, and carbamates is described. The scope of the fluorous N-O linker is exemplified by the synthesis of itopride, a drug used for the treatment of functional dyspepsia. Itopride was synthesized with the aid of fluorous purification methods and the product was isolated in good overall yield, with high purity.
“…The total number of libraries cited was 284, comparable to the 297 figure for 1999, bringing the cumulative total to over 1250 libraries published since 1992 − …”
An exhaustive compilation of biologically active libraries covering the years 1992-1997 was presented in a previous review [1a]. In that review, libraries were divided among 4 major categories, including those active against proteases, non-proteolytic enzymes, Gprotein coupled receptors, and non-G-protein coupled receptors. A generic structure for each library was provided as well as the structure of the most active member. The number of biologically active libraries reported in the literature during this time period (86 total) represents <25% of the total number of published library constructs. Disclosure of library synthesis without accompanying screening data is a more common occurrence. Because these types of libraries are equally important to the practicing combinatorial chemist, it was thought that a comprehensive listing of such libraries spanning the years 1992-1997 would be a useful supplement to the previous review [1a,b].Library constructs [2-248] listed herein are relegated to one of five tables. Table 1 is entitled 'Scaffold derivatization' and includes all constructs in which a multi-functional scaffold is modified in some fashion to create a library. An example of a construct found in Table 1 would be the sequential addition of three nucleophiles to trichloropyrimidine. Table 2, entitled 'Acyclic synthesis', lists all linear constructs such as those derived from multi-component Ugi condensations.
“…A recent application of a hydroxylamine linker toward the synthesis of tertiary methylamines has been reported , using the same quaternization and cleavage principal as REM and the vinyl sulfone linkers (Scheme ). 65 …”
Section: E Traceless Linkers For Tertiary Amine Synthesismentioning
confidence: 99%
“…Tertiary methylamines were synthesized via a hydroxylamine linker 235 using a Boc-protection/Nalkylation/Boc-deprotection/reductive alkylation protocol (4 steps) 124 or a Boc-protection/N-alkylation/Bocdeprotection/benzotriazole Mannich base/Grignard reaction protocol (5 steps) 125 to give resin-bound tertiary hydroxylamines 236. Cleavage was achieved via quaternization with methyl triflate to give 237, followed by a base-induced fragmentation to release tertiary amines in 18-80% overall yields with >99% purity.…”
Section: E Traceless Linkers For Tertiary Amine Synthesismentioning
confidence: 99%
“…Cleavage was achieved via quaternization with methyl triflate to give 237, followed by a base-induced fragmentation to release tertiary amines in 18-80% overall yields with >99% purity. The linker was shown to be stable to strong acids (TFA), 124 organometallic nucleophiles (Grignard reagents), 125 and organometallic reducing agents (LiAlH 4 ). 124 The linker was employed in the synthesis of the MAO inhibitor R-methylpargyline 239 (75%) and the analgesic Tramadol 240 (57%) to demonstrate its application toward medicinal active compounds.…”
Section: E Traceless Linkers For Tertiary Amine Synthesismentioning
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