4.6- Dimethoxy-1 - -1 //-indole

Again, if 3,5-dimethoxyaniline is used, 4,6-dimethoxy-indole should result. 

EXTENSIONS AND COMMENTARY This compound, having no detectable activity even at the milligram / kilo level, pretty much condemns the 5,6-dimethoxy indole pattern. Quite a few closely related derivatives have been made there is the N,N-dimethyl (5,6-MeO-DMT), the N,N-diethyl (5,6-MeO-DET), the N,N-dibutyl (5,6-MeO-DBT) and the three famous heterocyclic ring compounds, the pyrrolidyl (5,6-MeO-pyr-T), the piperidyl (5,6-MeO-pip-T) and the morpholyl (5,6-MeO-mor-T) compounds. They were all synthesized and characterized in the 1960 s, but I have no record of any having been tried in man. 

Additional examples of conversion of 0-acylanilides to indoles by low-valent titanium were reported. <94CB1125> A number of 5-methoxy and 5,6-dimethoxy indoles were prepared, including compound 39 which is a precursor of the tumor inhibitor zindoxifene. 

Indole, 3-(dialkylaminomethyl-) alkylation, 4, 275 Indole, 2,3-dibromo-synthesis, 4, 215 Indole, 2,6-dibromo-3-methyl-synthesis, 4, 215 Indole, 1,3-dichloro-synthesis, 4, 214 Indole, dihydrodehydrogenation, 4, 283, 311 in non-silver photography, 1, 383 Indole, 2,3-dihydro-synthesis, 4, 327, 352 Indole, 2,3-dihydroxy-tautomerism, 4, 37, 199 Indole, 4,6-dimethoxy-... 

In 1961 Acheson and Hands obtained 3-methyl-l-(2-nitroethyl)-indole (354) in low yield by the addition of nitrocthylene to 3-methyl-indole magnesium iodide. These authors also obtained 5-benzyloxy-l,3-bis(2-nitroethyl)iiidole (355) and 5,6-dimethoxy-3-(2-nitroethyl)-indolo (356) by the action of nitrocthylene on 5-henzyloxy- and 5,G-dimethoxyindolc magnesium iodide, respectively. They excluded the ]jossibility that the products 354, 355, and 356 had the isomeric indolenine structures on the basis of their absorption spectra and chemical properties. 

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Dimethoxy-3-(2-hydroxy-athyl)-2,3-dihydro-aus 5,6-Dimethoxy-2-oxo-3-(athoxycarbonyl-methyl)-2,3-dihydro-indol und Lithiumalanat 250... 

In the frame of a medicinal project at J J Pharmaceutical Research and Development aimed at designing new potent and selective glycogen synthase kinase-3/i (GSK-3/3) inhibitors, the C-3 derivatization of the 1-methyl-4-[l-alkyl-lff-indol-3-yl]-lff-pyrrole-2,5-dione scaffold was explored [31]. Microwave-assisted Stille reaction of 3-chloro-l-methyl-4-[l-alkyl-lff-indol-3-yl]-lH-pyrrole-2,5-diones with (2,4-dimethoxy-5-pyrimidinyl)(tributyl) stannane at 200 °C yielded in 6 min the desired 3,4-diaryl-lff-pyrrole-2,5-diones in moderate yields (Scheme 12). 

CN 5,6-dimethoxy-2-methyl-3-[2-(4-phenyl-l-piperazinyl)ethyl]-l//-indole... 

To date, there are only few examples of applying the VNS reaction in the synthesis of natural products. Several natural products such as O-methylnordehydrobuffotenine (Scheme 9.10),91 an alkaloid of animal origin, l,3,4,5-tetrahydro[cd]indole (Scheme 9.11),92 and 7,8-dimethoxy-2-oxo-l,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline as key intermediates for marine alkaloids (Scheme 9.12)93 have been prepared via VNS reactions. 

Indene, 6,7-dimethoxy-3-methyl-2-CARBETHOXY-, 40, 43 Indene, 44, 63 hydroxylation of, 41, 53 Indole, conversion to indole-3-acetic acid, 44, 64... 

Synthese des 5,6,7-Trimethoxy-indols und des 6,7-Dimethoxy-bufotenin methyl-athers, by E. Hardegger and H. Corrodi, Pharm. Acta Helv., 39 (1964) 101-107. 

ICS 205-930 = (3-tropanyl)-IH-indole-2-carboxylic acid ester DOM = 2,5-dimethoxy-4-dimethylbenzene ethamine... 

The system Ru2(OAc) Cl/O2/toluene/50°C oxidisedR CH NHR to imines R CH=NR converted 1,2,3,4-tetrahydroisoquinoline to the 3,4-dihydroisoquinoline with isoquinoline, and 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline to 6,7-dimethoxy-3,4-dihydro-iso-qninoline (cf. mech. Ch. 1) [18], Such oxidations were also catalysed by TPAP/NMO/PMS/CH3CN, e.g. the conversion of indoline to indole (in which indoline nndergoes a donble-bond shift and aromatisation), and the oxidation of 1,2,3,4-tetrahydroqninoline to 3,4-dihydroquinoline (Fig. 5.1, Table 5.1) [19]. 

TRYPTAMINE, 5,6-DIMETHOXY-N-ISOPROPYL-N-METHYL INDOLE, 5,6-DIMETHOXY-3-[2-(ISOPROPYLMETHYLAMINO)ETHYL] 5,6-DIMETHOXY-N-ISOPROPYL-N-METHYLTRYPTAMINE 5,6-DIMETHOXY-3-[2-(ISOPROPYLMETHYLAMINO)ETHYL]INDOLE... 

The latter was dissolved in 100 ml of absolute ethanol, the mixture acidified with 400 ml of saturated ethanolic hydrogen chloride, and a stream of hydrogen chloride gas was passed through the mixture causing the temperature to rise to 80°C. The solid which separated from the reaction mixture was collected after standing overnight, and washed with cold absolute ethanol to give 38 g of crude 2-carboxy-5,6 -dimethoxy-3-(2-hydroxyethyl) indole. 

The latter was suspended in 300 ml of absolute ethanol and the solution saturated with anhydrous hydrogen chloride for one hour. The mixture was allowed to stand for two hours, and the solid which separated was collected and dried to give 24 g of 2-carbethoxy-5,6-dimethoxy-3-(2-chloroethyl)indole, M.P. 179-181°C. 

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