21777-18-4

Upstream product

• 487-89-8 Indole-3-carboxaldehyde 
• 2537-48-6 diethyl 1-cyanomethylphosphonate 
• 372-09-8 cyanoacetic acid 
• 20356-45-0 3-(1H-indol-3-yl)-3-oxo-propionitrile 
• 6286-56-2 3-<(2-cyano-2-ethoxycarbonyl)ethenyl>indole 
• 16640-68-9 cyanomethylene triphenylphosphorane 
• 700-06-1 indole-3-carbinol 
• 120-72-9 indole 
• 107-13-1 acrylonitrile 

Downstream Products

• 6245-89-2 Homotryptamine 

Relevant academic research and scientific papers

γ-Regioselective Functionalization of 3-Alkenylindoles via 1,6-Addition to Extended Alkylideneindolenine Intermediates

Alkylideneindolenines are widely employed key electrophilic intermediates for the α-functionalization of the C-3 side chain of indoles. However, the reactivity of their extended (vinylogous) counterparts has not been carefully explored so far. These intermediates can undergo 1,4- or 1,6-addition with functionalization at α- or γ-position of the side chain, resulting in regioisomeric mixtures of products. This work demonstrates that a complete γ-regioselectivity can be achieved in the reaction of 3-indol-3-yl allylic alcohols with various nucleophiles. This process is catalysed by just 1 mol% zinc(II) triflate at room temperature and entails the 1,6-selective addition of the nucleophile to an extended protonated alkylideneindolenine generated in situ. Indoles, pyrroles, anilines and thiols can be efficiently used as nucleophilic partners for this reaction, delivering the corresponding 3-vinyl substituted, γ-functionalised indole products in moderate to good yields. (Figure presented.).

Palladium-catalyzed intermolecular C3 alkenylation of indoles using oxygen as the oxidant

A general and efficient palladium-catalyzed intermolecular direct C3 alkenylation of indoles using oxygen as the oxidant has been developed. The reaction is of complete regio- and stereoselectivity. All products are E-isomers at the C3-position, and no Z-

L-Proline-catalyzed Knoevenagel condensation: A facile, green synthesis of (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-indol-3-yl) acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a-e) and 4(a-e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl) acrylates 3(a-e) and 5(a-e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a-e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a-e) and 7(a-e). Copyright Taylor & Francis Group, LLC.

Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators

Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His55 and Thr254 residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (Ki = 5.5 μM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.

Borrowing hydrogen: Indirect "Wittig" olefination for the formation of C-C bonds from alcohols

The successful development of an indirect three-step domino sequence for the formation of C-C bonds from alcohol substrates is described. An iridium-catalysed dehydrogenation of alcohol 1 affords the intermediate aldehyde 2. The desired C-C bond can then be formed by a facile Wittig olefination, yielding the intermediate alkene 3. In the final step the alkene is hydrogenated to afford the indirect Wittig product, the alkane 4. The key to this process is the concept of borrowing hydrogen; hydrogen removed in the initial dehydrogenation step is simply borrowed by the iridium catalyst. Functioning as a hydrogen reservoir, the catalyst facilitates C-C bond formation before subsequently returning the borrowed hydrogen in the final step. Herein we present full details of our examination into both the substrate and reaction scope and the limitations of the catalytic cycle. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Synthetic applications of 3-(cyanoacetyl)indoles and related compounds

Various synthetic applications of 3-(cyanoacetyl)indoles, as well as syntheses of some related indoles, have been investigated. Diethyl 2-(1H-indol-3-yl)-2-oxoethylphosphonate and a methyl derivative thereof have been prepared in one step from indole. Moreover, it was demonstrated that 3-(cyanoacetyl)indoles are useful starting materials for the preparation of for example 3-(1H-indol-3-yl)-3-oxopropanamides, 3-heteroarylindoles or 3-heteroaroylindoles.

1,3-Dinitropropanes: Intermediates to 1,3-diaminopropanes

Reduction of malodinitriles 4 and 10 to the corresponding diamines does not work. - Reduction of dinitro-2-(indol-3-yl)-propanes 13 and 16 and subsequent reaction with K2PtCl4 afford the corresponding dichloroplatinum(II) complexes 14 and 17. Complexes 17 show weak binding affinities to the estrogen receptor and no antitumor activity towards MCF-7 and MDA-MB-2231-cell lines. - Twofold addition of nitromethane to aldehyde 24 is possible.

THE SYNTHESIS OF 3-VINYLINDOLES AND 11H-5-CYANOBENZOCARBAZOLE

The synthesis of 3-vinylindoles through Wadsworth Emmons reactions with 3-formyl and 3-acylindoles is described.Altough 3-formylindoles react directly with phosphonate derivatives, 3-acylindoles need prior activation by N-sulphonation. 11H-5-Cyanobenzocarbazole has been prepared by the oxidative cycloaddition of E-3-(indol-3'-yl) propenonitrile and benzyne.