2-Butyl-3-methyl-indole

Methyl-2-(tri-n-butyl-stannyl)indole 4-Bromobenzonitrile, Pd(PPh3),Cl, 91 [2]... 

T rimethylsilylethoxy-methyl)-2Ttri-n-butyl-slannyl)indole 2-Bromopropene, PdfPPhjljClj 62 [2]... 

TRYPTAMINE, N-BUTYL-N-METHYL INDOLE, 3-[2-(BUTYLMETHYLAMINO)ETHYL] N-BUTYL-N-METHYLTRYPTAMINE 3-[2-(BUTYLMETHYLAMINO)ETHYL]-INDOLE... 

The synthetic utility of many of the substitution reactions described so far is limited because there are well-established thermal routes to the same products. However, a third group of photochemical nucleophilic substitutions involves aryl halides and nucleophiles based on sulfur, phosphorus or, of particular importance, carbon. Two examples are the reaction of bromobenzene with the anion of t-butyl methyl ketone 13.12), and the replacement of bromine by cyanomethyl in 2-bromopyridine (3.13). This type of reaction offers a clear advantage over lengthy thermal alternatives, and intramolecular versions have been used in the synthesis of indoles (e.g. 3.14) or benzofurans from o-iodoaniline or o-iodoanisole respectively. 

A solution of NaHMDS (1 M solution in THF 12.69 mL, 12.69 mmol, 1.2 equiv) was added dropwise to a solution of indole (1.24 g, 10.58 mmol, 1 equiv) in THF (130 mL) at —78 °C. After 30 min, methyl chloroformate (1.07 mL, 13.15, 1.3 equiv) was added dropwise and the reaction mixture was allowed to warm to room temperature for 4 h. Then, the reaction mixture was diluted with EtOAc and washed with a sat. NH4CI solution. The aqueous phase was extracted 2 times with EtOAc, and finally the organic phases were washed with brine, dried over MgS04 and concentrated. After silica gel column chromatography (20 1 hexane EtOAc), 1.43 g of the methyl l//-indole-l-carboxylate was isolated (77 %). fcrt-Butyl 17f-indole-l-carboxylate[244]... 

Hydrogenation of i-butyl nicotinate methobromide, followed by hydrolysis of the 1-methyl-3-tert-butoxycarbonyl-1,4,5,6-tetrahydro-pyridine product (205) in the presence of indole affords, on decarboxylation, the -substituted derivative (206) (325). The formation of... 

The Diels-Alder reactions of the methyl or ethyl ester of benzenesulfonylindole-2-acrylic acid with several l-alkoxycarbonyl-l,2-dihydropyridines are reported and only a single stereoisomer was obtained, as in the case of l-methoxy(ethoxy)-carbonyl-1,2-dihydropyridines. However, when the Diels-Alder reaction of 17 was carried out with 8g[R = (CHsjsC], a mixture of two stereoisomers 18gand25were obtained in a 1 1 ratio (65% total yield). The bulky rerr-butyl group creates sufficient steric interference with the indole ring to cause the loss of stereochemistry ... 

Azatricyclo[2.2.1.02 6]hept-7-yl perchlorate, 2368 f Azetidine, 1255 Benzvalene, 2289 Bicyclo[2.1.0]pent-2-ene, 1856 2-/ert-Butyl-3-phenyloxaziridine, 3406 3 -Chloro-1,3 -diphenyleyclopropene, 3679 l-Chloro-2,3-di(2-thienyl)cyclopropenium perchlorate, 3388 Cyanocyclopropane, 1463 f Cyclopropane, 1197 f Cyclopropyl methyl ether, 1608 2,3 5,6-Dibenzobicyclo[3.3.0]hexane, 3633 3,5 -Dibromo-7-bromomethy lene-7,7a-dihy dro-1,1 -dimethyl-1H-azirino[l,2-a]indole, 3474 2.2 -Di-tert-butyl-3.3 -bioxaziridinc, 3359 Dicyclopropyldiazomethane, 2824 l,4-Dihydrodicyclopropa[ >, g]naphthalene, 3452 iV-Dimethylethyl-3,3-dinitroazetidine, 2848 Dinitrogen pentaoxide, Strained ring heterocycles, 4748 f 1,2-Epoxybutane, 1609 f Ethyl cyclopropanecarboxylate, 2437 2,2 -(l,2-Ethylenebis)3-phenyloxaziridine, 3707 f Methylcyclopropane, 1581 f Methyl cyclopropanecarboxylate, 1917 f Oxetane, 1222... 

A variety of other carbon nucleophiles have been alkylated with alcohols including malonate esters, nitroaUcanes, ketonitriles [119, 120], barbituric acid [121], cyanoesters [122], arylacetonitriles [123], 4-hydroxycoumarins [124], oxi-ndoles [125], methylpyrimidines [126], indoles [127], and esters [128]. Selected examples are given in Scheme 35. Thus, benzyl alcohol 15 could be alkylated with nitroethane 147, 1,3-dimethylbarbituric acid 148, phenylacetonitrile 149, methyl-pyrimidine 150, and even f-butyl acetate 151 to give the corresponding alkylated products 152-156. 

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

Discriminative stimulus effect. Rhesus monkeys, trained to discriminate A-9-THC from vehicle in a two-lever drug discrimination procedure, were tested with a variety of psychoactive drugs, including cannabinoids or drugs from other classes. The results indicated that A-9-THC discrimination showed pharmacological specificity, in that none of the noncannabinoid drugs fully substituted for A-9-THC. The classical cannabinoids, A-9-THC and A-8-THC, and the novel cannabinoids, WIN and l-butyl-2-methyl-3-(l-naphthoyl)indole, produced full dose-dependent substitution for A-9-THC in all monkeys. A heptyl indole derivative failed to substitute for A-9-THC, but it also did not displace pH] CP-55,940 from its binding site . ... 

OH-DPAT = 8-Hydroxy-2-(di-n-propylamine)tetralin CP93129 = 5-Hydroxy-3(4-l,2,5,6-tetrahydropyridyl)-4-azaindole LY334370 = 5-(4-fluorobenzoyl)amino-3-(l-methylpiperidin-4-yl)-l -indole fumarate SB204741 = A/-(l-methyl-5-indolyl)-/V -(3-methyl-5-isothiazolyl)urea WAY100635 = N-tert-Butyl 3-4-(2-methoxyphenyl)piperazin-l-yl-2-phenylpropanamide. 

Decarboxylation of 117 was effected by treatment of 117 with LiCl in hot, aqueous HMPA at 105 °C providing 118 as a mixture of diastereomers that were separated and carried forward individually. Protection of the secondary amide group as the corresponding methyl lactim ether was accomplished by treating 118 with trimethyloxonium tetrafluoroborate in dichloromethane that contained cesium carbonate. Next, the indole nitrogen atom was protected as the corresponding Boc derivative by treatment with dicarbonic acid bis(rm-butyl)ester in the presence of DMAP and the silyl ether was removed with tetrabutylammonium fluoride to provide diol 119 in 52-78% overall yield from 118. Selective conversion of the allylic alcohol to the corresponding... 

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