Indole-7-carbaldehyde, 1-methyl

Indole-7-carbaldehyde, 1-methyl-synthesis, 4, 83 Indole-3-carbaldehydes synthesis, 2, 251 Indole-2-carboxamide reduction, 4, 256 synthesis, 4, 360 Indole-3-carboxamide synthesis, 4, 347... 

Dicarbonylimidazole reacted with the anthranilic acid derivative (498) to produce the fused isoxazolone IV-oxide (499) (77ZOR462). Methyl nitroacetate reacted with indole-3-carbaldehyde to produce (500) (70KGS1505). Treatment of (501) with base gave 3,4,5-triphenyl-2-isoxazoline IV-oxide (Scheme 142) (69JOC984). The reaction was reported to be a direct displacement as (502) did not give a product and no incorporation of deuterium was found using DOMe. 

This trend is also observed in the reactions with nitrogen- and carbon-centered nucleophiles (2001H425). Thus, the reaction of 109 with sodium indolyl in DMF affords methyl 2-(indol-l-yl)indole-3-carboxylate (188, 77%). In better yield, 2-(indol-l-yl)indole-3-carbaldehyde (189, 95%) is formed in the corresponding reaction (99H1157) of 115a (Scheme 28). Sodium imidazolyl reacts with 109 in DMF at 60°C to afford methyl 2-(imidazol-l-yl)indole-3-carboxylate (190,28%), methyl indole-3-carboxylate (191,11 %), and unreacted 109 (36%). In contrast, under the same conditions, 110 and 115a provide higher yields of methyl 2-(imidazol-... 

Thallation of l-methoxyindole-3-carbaldehyde with thallium trisfluo-roacetate followed by treatment with potassium iodide gave the 4-iodo derivative in 91% yield, and this has been converted into many other 1-methoxyindole derivatives (86CPB677). When the thallated indole reacted with methyl acrylate in the presence of a catalytic quantity of pal-ladium(ll) acetate, 47% of the product was the 4-derivative 160, but 11% of the 5-isomer was also formed (86CPB4116). 

A versatile and convenient method for the synthesis of substituted benzo[o]carbazoles and pyrido[2,3-a]carbazoles has recently been developed [59]. Treatment of 2-(o-tolyl)- or 2-(3-methyl-2-pyridyl)-substituted indole-3-carbaldehydes (obtained by Suzuki reaction) with potassium tert-butoxide in DMF at 70-80 °C under irradiation by a 400 W high-pressure mercury lamp afforded benzo[a] carbazoles and pyrido] 2,3-o] carbazoles, respectively, in good yields (Eq. (30)). 

Reduction of the mixture of l-[(2-aziranyl)methyl]-177-indole-3-carbaldehydes 926 was readily achieved with NaBH4 in MeOH to produce l-[(2-aziranyl)methyl]-177-indol-3-yl methanols 927, reductive cyclization of which is a route to (l,la,2,8,8a,8b-hexahydroazireno[2, 3 3,4]pyrrolo[l,2- ]indol-8-yl)methanol 928 (Scheme 180) <1997JOC1083>. 

Benzindolizidine systems 963 are generated in moderate yields by a hexabutylditin-mediated consecutive radical addition, cyclization, and oxidation process from easily accessible l-(2-iodoethyl)indoles 962 and methyl acrylate, in one step (Scheme 186) <2000TL10181>. l-(2-Iodoethyl)-l//-pyrrole-2-carbaldehyde was also subjected to the tandem radical addition-cyclization process, and the indolizidine derivative 964 was isolated in modest yield as the major product together with a small amount of starting material (Equation 229). 

A slurry of sodium hydride (88.16 mmol) in 100 ml THF was cooled to 5°C and methyl acetoacetate (88.16 mmol) dissolved in 50 ml THF slowly added so that the temperature did not exceed 10°C. The mixture stirred 30 minutes, 1.6M butyllithium (90.12mmol) added dropwise, and the yellow solution stirred 20 minutes while cooling with ice. To this was added 3-(4-fluorophenyl)-l-isopropyl-lH-indole-2-carbaldehyde (53.32mmol) dissolved in 100 ml THF and the mixture stirred 45 minutes. Thereafter a thick yellow suspension formed, acetic anhydride (533.2 mmol) was added, and the solution stirred 15 minutes then warmed to ambient temperature. The reaction mixture was poured into 250 ml 1M HCl, extracted 3 times with EtOAc, washed twice with 50 ml brine, once with 100 ml of 5% NaHCOj, and 3 additional times with brine. It was dried, concentrated, and the product isolated as an orange oil. 

The preparation of other Step 1 analogues including (a) 3-(4-fluorophenyl)-l-isopropyl-, (b) 2-carbaldehyde-, (c) 2-carboxylic acid-, and (d) 2-carboxylic acid-lH-indole methyl ester, are described by the author in the current invention. 

A number of l-aryl-2-(3 -indolyl)ethylenes (20) have been prepared in good yield from indole-3-carbaldehyde. 2-Methyl-3-phthalimidopropanal can be converted into (21), which is hydrazinolysed to the expected amine, ... 

In the first route (Scheme 4), indoUne (5) is nitrated to 6-nitro-2,3-dUiydroindole (22, 92%). Apphcation of the tungstate method to 22 and subsequent methylation provide l-methoxy-6-nitroindole (9, 77%) via 8a. A Vilsmeier-Haack reaction (94%), followed by nitroaldol reaction (85%), leads 9 to l-methoxy-6-nitro-3-(2-nitrovinyl)indole (23) through 1-methoxy-6-nitroindole-3-carbaldehyde (10b). After selective reduction of the nitro-vinyl part of 23 with NaBH4, the resultant l-methoxy-6-nitro-3-(2-nitro-ethyl)indole (24,84%) is treated with Zn/HCl and then AC2O to give 21 (81%). Reduction of 24 with Zn/AcOH produces 6-amino-l-methoxytryptamine (25, 30%). 

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