Pyrazino 2,3-/? indoles

The synthesis of pyrazino-indoles has been described starting from 2-carbonyl-l-propargylindoles 241 and ammonia. The reaction gave a mixture of isomers, 242 and 243 in Scheme 90, and was optimized using... 

The intramolecular cyclization of J-iminoacetylenes to pyrazino[l,2-a]indoles described by Abbiati [67] is a new example of modification of selectivity. When 1-propargyl indoles 79 were treated in a sealed tube at 100 °C with 2 m ammonia in methanol, the corresponding pyrazino indoles 80 and 81 were obtained in good yields. Differences between the relative ratio of 80 and 81 were related to ... 

Reduction of the N(ll)=C(lltf) double bond of l,4-dihydro-2//-pyrazino[2,l-A quinazoline-3,6-diones 30 (R1 = indol-3-ylmethyl R2 = Me) and 31 (R1 = CH2-C6H4-C1- z Rz = Me) was effected with NaBH4. While the m-diastereomer, 30, retained its configuration, the /razw-diastereomer, 31, epimerized during the reaction. <1999JOC7233>. 

Although 7,14-dihydroxy-6H,13H-pyrazino[l,2- 4,5-,T]bisindole-6,13-dione can jn pr ncipie exist in two tautomeric forms of the dihydroxy compound 39 and the diketo form 40, only the dihydroxy is observed <2003OBC3396>. Presumably this is due to the enolizable 1,3-dicarbonyl moieties and the formation of the indole ring, therefore leading to aromaticity and a net overall stabilization. 

In addition, Hegedus and co-workers extended this chemistry to the /V-alkylation of 1-lithioindole with alkenes (PdC MeCN /THF/HMPA/EtsN/then H2) to afford A/-alkylindoles in 28-68% yields [411], Moreover, a similar reaction of N-allylindole 343 with nitriles leads either to 344a, 344b, or 344c depending on how the intermediate Pd-alkyl (or acyl) complexes are treated [431]. The formation of these pyrazino[ 1,2-a]indoles is similar to a nitrile-Ritter reaction. 

Mdrour studied the reaction of indole triflates with diamines to afford pyrazino[2,3-fc]indoles 374 and indolo[2,3-fejquinoxalines [467]. In the absence of palladium the yield of 374 is only 31% after 15 h. In some cases spiroindoxyls are formed. 

Hemkh. 0/100 George 1979 Mar ALKAL. braninated indole and pyrrole pyrazino bis-steroidal. POLYKET. bromophenols. high medium... 

The synthesis of the pyrazino[l,2-a]indole nucleus (64)/(65) was attained by intramolecular cyclization of several 2-carbonyl-1-propargylindoles (63) in the presence of ammonia. The reaction conditions were optimized using microwave heating and a... 

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

Invention Significance Pyrazino[l/,2 l,6]pyrido[3,4-b]indole-based... 

Table 1 Selected (6R-fran5 )-6-(l,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-pyrazino[l, 2, l,6]pyrido[3,4-b]indole-l,4-dione derivatives their and corresponding physical properties. H NMR data supplied by author...

Indole-2-carboxamides 146 underwent palladium-catalyzed intramolecular cyclization reactions to afford 3-carbo-lin-l-ones 147 or pyrazino[l,2- ]indol-l(27/)-ones 148, according to different reaction pathways (Scheme 31) <2003JOC7625>. Complete regioselectivity of the reactions was obtained in different reaction conditions. 

In a new simple synthesis of pyrazino[l,2-a]indole derivatives, 3-methylindole 157 was A-alkylated to 158, followed by treatment with formaldehyde and benzotriazole to produce the system 159. Displacement of the benzotriazolyl moiety with various nucleophiles gave the final products 160 <03JOC4938>. 

P,12aP)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxy-phenyl)pyrazino[2, l 6,l]pyrido[3,4-fc]indole-l,4-dione. 

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