Indoles, as starting

A versatile tryptophan synthesis which proceeds directly from indoles as starting materials was developed by Gilchrist[5], The alkylation reagent is the... 

Many of the formulas for indole ethylamines use indole as starting material or an indole type acid (indole-3-acetic acid), which are converted to tryptamine or directly to the active dialkyItryptamine or dimethyltryptamine. If your formula gives just tryptamine, then it will have to be converted to one of the active compounds. As usual I will give the intermediate formulas before getting into the active products. Indole and tryptamine can be purchased from many chemical suppliers, but they are watched very closely by the DEA. 

Imidazolone synthesis, 291 Imidoline, 259 Imipramine, 420 Indapamide, 349 Indazole synthesis, 350 Indoles, as starting material for benzodiazepines, 405 Indomethacin, 345 Indoramin, 344 Incfoxoie, 254, 340 Inflammation, 63 Influenza A, 18 Inhibition,... 

MK-677, an orally active spiroindoline-based growth hormone secretagogue (GHS) agonist, discovered by Merck and currently in Phase II clinical studies, was synthesized with a Fischer indolization as a key step. The synthesis of this agonist involved a Fischer indole/reduction process and was achieved in 48% overall yield from the relatively cheap starting material, isonipecotic acid 72. ... 

In addition to /3-diketones, /3-ketoacids and /3-ketoesters, cyanoacetic ester and related compounds are suitable starting materials. The arylhydrazones 4 thus obtained are of great importance as starting materials for the Fischer indole synthesis, as well as for the preparation of other iV-heterocycles. ... 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

Fischer indole disconnection reveals hydrazine (20) and symmetrical ketone (21) (Chapter T 30) as starting materials. The hydrazine can be made from (22) by nltrosatlon and reduction. 

A different type of synthesis, which leads to a benzannulated indolo[2,3-3][l,6]naphthyridine 15, is illustrated in Scheme 3 <1999TL3797>, and the use of an azaindolone as starting material may introduce an additional heteroatom into the indole moiety of the product, as in 16 (Equation 2) <1994TL1995>. The dipyrrolo[2,3-3 2, 3 -g][l,8]naphthyridine 18 is produced by reaction of the naphthyridine 17 with ethyl glycinate in the presence of a phase-transfer catalyst (Scheme 4) <2000PS(163)29>. 

It is interesting to note that this methodology allows the preparation of 4-functionalized indole derivatives starting from a simple acyclic precursor in a one-pot sequence. To prepare N-unsubstituted indoles, we choose the allyl moiety as a result to its stability to strong basic conditions and the variety of methods for its removal.[20] We therefore used an approach based on the isomerization/hydrolysis of the allyl groups with diisobutylaluminium hydride (DIBAL-H) and a... 

There are other ways to make these two compounds. One of the intermediates is five times more potent than 5-acetylgramine and less toxic than 5-acetyl-3-piperidinomethylindole, so I will also give this method. This method starts from scratch, so it is not necessary to have indole as a starting material. 

Compounds derived from indole have been extensively investigated as potential psychoactive dmgs. The construction of a tricyclic indole derivative starts by benzyltrimethylammonium hydroxide catalyzed Michael addition of 2-carbethoxy-indole (70-1) to acrylonitrile to give the adduct (70-2). In one of several alternatives... 

Syntheses of category Ilac can properly be called the most important category of indole synthesis. Fundamentally, the reason for this is the use of aniline or its derivatives as starting materials. Besides the easy availability of many aniline derivatives, the aromatic starting material is monofunctional whereas many other annelation procedures require a specific ortho substitution pattern in the aromatic starting material. 

Another way to secure a single indole as product from the Fischer indole synthesis is to make sure die reagents are symmetrical. These two examples should make plain the types of indole available from symmetrical starting materials. 

The first, and hitherto only, synthesis of lysergic acid was effected by the research group of Kornfeld et al. (50, 26). In this particular synthesis a X-acyl-2,3-dihydroindole derivative was used as starting material, thus allowing the formation of rings C and D by classical methods. Dehydrogenation of the 2,3-dihydroindole system to the indole system was only effected in the last stage so that the formation of the benz[c,d]-indoline system was prevented. 

The title compound, mapindolol 198, a potent /7-adrenoceptor blocking (antihypertensive) agent, has been synthesized200 by the Madelungs method of indole synthesis using [l-14C]acetyl chloride as starting material (equation 80). 

Deprotonation of indoles 128 followed by alkylation with 2-methyloxirane led to the secondary alcohols 129 that were used as starting compounds in the preparation of substituted 2-(l//-indol-l-yl)-l-methylethylamines 130, novel agonists of 5HT2C receptors. Sn2 reaction of the corresponding mesylates with sodium azide and reduction of the azides with either hydrogen or LiAlH4 produced amines 130 in excellent yields (Scheme 28) <1997JME2762>. 

A highly flexible catalytic one-pot procedure for the synthesis of indoles employing or/ o-chloro-substituted l-phenyl-2-alkyl-alkynes or phenyl(aminoalkyl)alkynes as starting materials through a reaction catalyzed by Cp2TiMe2 has been reported.1916... 

---