Synthesis of (trimethylsilyl)thiazoles and reactions with carbonyl compounds. Selectivity aspects and synthetic utility

Dondoni, Alessandro; Fantin, Giancarlo; Fogagnolo, Marco; Medici, Alessandro; Pedrini, Paola

doi:10.1021/jo00243a029

Cited by 95 publications

(43 citation statements)

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“…This could be achieved following the method described by Dondoni et al,19 which consists of a C-5 regioselective lithiation of 2-trimethylsilylthiazole (2-TST) in ether since the 5-lithio derivative was found to be unstable in THF at À78 C. 14c Thus, starting with 2-TST (purchased or easily prepared 19 from the readily available 2-bromothiazole, Scheme 2), a C-5 lithiation was carried out followed by boronation using triisopropyl borate. Transesterification of the intermediate obtained was achieved by treatment with pinacol followed by adjusting the pH to 5 using acetic acid.…”

Section: Discussion and Resultsmentioning

confidence: 99%

Synthesis of 5-arylthiazoles. Comparative study between Suzuki cross-coupling reaction and direct arylation

Primas

Bouillon²,

Lancelot

et al. 2009

Tetrahedron

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Section: Discussion and Resultsmentioning

confidence: 99%

Synthesis of 5-arylthiazoles. Comparative study between Suzuki cross-coupling reaction and direct arylation

Primas

Bouillon²,

Lancelot

et al. 2009

Tetrahedron

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“…74,75 Compound 12f was prepared by Michael addition of N-methyl-3-phenylpropylamine to enone 7. Treatment of 8 with TiCl 4 followed by N-methyl-3-phenylethylamine provided 12h.…”

Section: Chemistrymentioning

confidence: 99%

Structure−Activity Relationships of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

et al. 2007

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A systematic study of the structure-activity relationships (SAR) of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, K i = 2.6 nM) with 5hh (aryl = 3-Cl-Ph, K i = 900 pM) being 5-fold more potent than 2b. Conformationally-restricted C2 side chains were examined and many provided exceptionally potent inhibitors of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO 2 ), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, K i = 3 nM or 13d, 2-position OH, K i = 8 nM) comparable in potency to 2b. Proteomicwide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.The enzyme fatty acid amide hydrolase (FAAH) is the primary catabolic regulator of several bioactive lipid amides in vivo, including anandamide (1a) and oleamide (1b). 1-4 The central nervous system distribution of FAAH suggests that it degrades neuromodulating fatty acid amides at their sites of action and is intimately involved in their regulation. 5 Fatty acid amide hydrolase is currently the only characterized mammalian enzyme that is in the amidase signature family bearing an unusual catalytic Ser-Ser-Lys triad. 1,4,6-8 Recently, the crystal structure of FAAH cocrystallized with an irreversibly-bound arachidonyl fluorophosphonate confirmed its unusual catalytic triad and provided structural details of this enzyme. 1 Both anandamide (1a) 9 and oleamide (1b) 10-12 have emerged as prototypical members of the class of bioactive lipid amides 13,14 that serve as chemical messengers (Figure 1). Anandamide (1a), the most recognized member of the endogenous fatty acid ethanolamides, 15 binds and activates both the central type-1 (CB1) and peripheral type-2 (CB2) cannabinoid receptors. Anandamide (1a), and members of the cannabinoid family, 16 have been implicated in the modulation of nociception, 17-19 feeding, 20,21 emesis, anxiety, 22 cell proliferation, 23,24 inflammation, 25 memory 26 and neuroprotection after brain injury. 27 Thus, the Due to the potentially exciting therapeutic potential of inhibiting FAAH, there has been increasing interest in the development of potent inhibitors (Figure 2). 22,45-60 These include the discovery that the endogenous sleep-inducing molecule 2-octyl α-bromoacetoacetate is an effective FAAH inhibitor, 55 a series of reversible inhibitors bearing an electrophilic ketone 46,54,56 (e.g., trifluoromethyl ketone-based) that have not proven selective for FAAH over other mammalian serine hydrolases 61 and a set of irreversible inhibitor...

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“…By the lithium 'azido transfer' protocol, simple 2-and 5-azidoazoles were obtained following the protocol illustrated in Schemes 4 and 5 22 . The 2-lithium derivatives of Nmethylimidazole, 23 1,3-thiazole, 24 benzo-1,3-thiazol, 25 and N-methylpyrazole, 26 prepared according to the procedures described, 27 react quantitatively with tosyl azide, resulting in solid azole-2-tosyltriazenyl lithium salts. Final treatment with tetrasodium pyrophosphate produces the appropriate 2-azidoazoles in fairly good yields (63-81%).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, reactivity, and electronic structure of multifarious, five-membered heteroaryl and heteroaroyl azides

Zanirato¹

2009

Arkivoc

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The aim of this account is to review our most important outcomes -published during the last 30 years -concerning the azido group that is linked to five-membered heteroaryl and heteroaroyl systems. The main focus of this manuscript is on the 'azido transfer' reaction to heteroaryl azides, and the peculiar thermal and chemical reactivities of these precursor species. In particular, the following topics are considered: (a) the ring cleavage of α-heteroaryl azides to form 4-cyano-1,3-heterodienes, (b) the reactivity of thermally generated β-nitrene, (c) the 1,3-dipolar cycloaddition of the azido group to various terminal or 1,2-disubstituted alkenes or alkynes to form nitrogen-containing biheterocycles, (d) the generation of electrophile nitrenium ions with Lewis acids, (e) the conversion of heteroaroyl azides into isocyanates, and (f) the 1,3-dipolar cycloadditions of heteroaroyl azides with 'activated' olefins. The concurrence and discordance of the thermal and chemical behaviour between heteroaryl azides, and the related substituted phenyl azides will be critically considered here.

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Synthesis of (trimethylsilyl)thiazoles and reactions with carbonyl compounds. Selectivity aspects and synthetic utility

Cited by 95 publications

References 2 publications

Synthesis of 5-arylthiazoles. Comparative study between Suzuki cross-coupling reaction and direct arylation

Synthesis of 5-arylthiazoles. Comparative study between Suzuki cross-coupling reaction and direct arylation

Structure−Activity Relationships of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

Synthesis, reactivity, and electronic structure of multifarious, five-membered heteroaryl and heteroaroyl azides

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