Pyrrolo 2.3-/ pyridine

Most of the synthetic routes to the compounds start from a six-membered ring heterocycle. As found in the previous review <1996CHEC-II(7)167>, the focus of many of the studies has been on the pyridine series-pyrrolo-pyridines, furopyridines, and thienopyridines. Within each of these classes of compounds, the [2,3-3] isomers have, by far, received the most attention. Also, as found in the previous review, some of the ring systems have not been investigated at all. Since that time, there has been much interest in thienopyridines because of the wide variety of biologically active compounds that originate from derivatives of thienopyridines (see Section 10.06.12.3). Much of the chemistry of furopyrans involves partially or fully reduced derivatives. There are few literature references to the parent series listed in Figure 6 however, there has been considerable activity with the reduced derivatives. 

The reaction used for the construction of the starting material for a pyrrolo-pyridine involves the standard pyrimidine chemistry discussed in Chapter 9. Thus condensation of the substituted cyanoacetate (16-1) with acetamidine leads to the... 

Interesting constructs of molecules such as pyrrolo-pyridines, pyrrolo-quinolines, pyrrolo-pyrazines, pyrrolo-quinoxalines and pyrrolo-pyrimidines could be constructed by intramolecular Chichibain-type reaction. Davis and co-workers were the first to show the first of these examples, where p-methylazines react with nitriles to give the corresponding fused bicycle in the presence of excess base (2.5 equiv). For example, P-picoline reacts with benzonitrile in the presence of LDA to give the pyrrolo-pyridine adduct 61 in a 90% yield and traces of 62a. Under similar conditions and if... 

Fluorophenyl)indol-l-ylzinc chloride 3-(Pyridin-3-yl)-l /7,3-f -pyrrolo[l, 2-c]thiazole-7-carbonyl chloride >45 [8]... 

Pyrrolo[2,3-c]pyridine, 2-hydroxy-IR, 4, 502 (74JCS(P1)1531> Pyrrolo[3,2-6]pyridine, 1,3-dibenzyl-2-oxo-IR,4, 502 (72JOC51)... 

Pyrindole — see Pyrrolo[l,2-a]pyridine Pyrithyldlone as sedative, 1, 165 Pyromeconic acid from comenic acid, 3, 710 occurrence, 3, 692... 

Pyrrolo[3,4-d]pyridazinium salts, 2,3-dimethyl-synthesis, 4, 291 Pyrrolo[ 1,2-6]pyridazinones oxidation, 4, 298 Pyrrolo[2,3-6]pyridine, 1-acetyl-cycloaddition reactions, 4, 509 Pyrrolo[2,3-6]pyridine, 3-bromo-nitration, 4, 505... 

Pyrrolo[2,3-6]pyridine, 2,3-dihydro-electrophilic substitution, 4, 503 nitration, 4, 512 synthesis, 4, 520... 

Pyrrolo[2,3-6]pyridine, 2-methyl-Reimer-Tiemann reaction, 4, 508 Pyrrolo[2,3-6]pyridine, 4-methyl-hydrogen exchange, 4, 502 reaction with aldehydes, 4, 503 reaction with benzaldehyde, 4, 511... 

Pyrrolo[3,2-6]pyridine, 2-methyl-synthesis, 4, 527 Pyrrolo[3,2-c]pyridine, 4-amino-nucleophilic reactions, 4, 507 Pyrrolo[3,2-c]pyridine, 2,3-dihydro-reactions, 4, 512... 

Pyrrolopyridines — see Indolizines Pyrrolo[l,2-a]pyridines — see Indolizines Pyrrolo[2,3]pyridines alkylation, 4, 504 synthesis, 4, 528... 

Pyrrolo[2,3-c]pyridines — see also 6-Azaindoles reaction with O-mesitylhydroxylamine, 4, 508 synthesis, 4, 516, 522 tautomerism, 4, 502 UV spectra, 4, 501... 

Pyrrolo[3,2-6]pyridines — see also 4-Azaindoles hydrogen exchange, 4, 502 quatemization, 4, 503 synthesis, 4, 527... 

Pyrrolo[2,3-6]pyridinium iodide, 1,7-dimethyl-reduction, 4, 508 Pyrrolo[3,2- 6]pyridin-2-ones spectra, 4, 502... 

H-Pyrrolo[3,2-6]pyridin-2( 1 H)-ones synthesis, 6, 630 1 H-Pyrrolo[3,2-c]pyridin-4-ones synthesis, 4, 277... 

DMAD) in boiling toluene, the bicyclic compound pyrrolo[3,4-c]pyridine being obtained (89CB1673) (Scheme 11). 

Phthalimidobutyl)-2,3,4,4u,5,6-hexahydro-l//-pyrazino[l,2-u]quino-line was obtained in the reaction of 2,3,4,4u,5,6-hexahydro-l//-pyrazino[l,2-u]quinoline and A-(4-bromobutyl)phthalimide in boiling MeCN in the presence of K2CO3 (97MIP12). 2,3,4,4u,6,7-He-xahydro-l//-pyrazino[l,2-ujquinolines were N-alkylated with 3-dimethylaminomethyl-l//-pyrrolo[2,3-6]pyridine and a mixture of l//-pyrrolo[2,3-6]pyridine and 37% aqueous H2CO in aqueous AcOH in the presence of NaOAc (96USP5576319). 3-[3-Substituted 2-propen-l-yl]-2,3,4,4u, 5,6-hexahydro-l//-pyrazino[l,2-u]qui-... 

The derivative from an isomeric fused system has been described as a sedative-hypnotic compound. The synthesis starts by condensation of the aminopicoline 32 with the haloketone 33. The resulting pyrrolo[l,2-a]pyridine 34 then undergoes a Mannich reaction with formaldehyde and dimethylamine to give the aminomethylated derivative 35. After quatemization of the di-methylamino group in 35 with methyl iodide, the ammonium group is displaced by cyanide to... 

Thermolysis of the 3-acyl-3/f-azepine 32 in Decalin at 250°C also gives the phenacylpyridine but in much reduced yield (6%). In a similar manner, 4-chloro-yV,/V-diethyl-3-phenacylpyridin-2-amine (53 % bp 160 C/0.18 Torr) is produced by the photolysis or thermolysis of 3-benzoyl-5-chloro-Ar,Ar-diethyl-3/f-azepin-2-amine.246 However, if the 3ff-azepine bears a secondary amine residue at the 2-position, e.g. 36, then photolysis or thermolysis yields a pyrrolo[2,3-/>]pyridine by intramolecular cyclization of the 3-phenacylpyridin-2-amine intermediate. 

The mechanism of attack of 1,3-dipolar reagents on fluoroalkenes can be considered to be either stepwise or concerted. Heteroaromatic N-imines react by a stepwise 1,3 addition to perfluoroalkenes and -alkynes to give fluorinated pyrazolo[l,5-a]pyridines [82JCS(P1)1593]. Pyridinium /-butoxycarbonylmethylide with fluoroalkenes gave pyrrolo[l,2-a]pyri-dines [86JCS(P 1) 1769] and indolizines (22) are obtained with pyridinium phenacylide [91JFC(51)407]. 

Treatment of 1,2,4-triazines 91a-91e with the electron-deficient die-nophile dimethyl acetylenedicarboxylate gave products, depending on the substituents [77LA( 10) 1718]. Pyrrolo-[2, -/][ ,2,4]triazines 92 were obtained via [4 + 2]-cycloaddition [77LA(9)1413, 77LA( 10)1718] with 91, but interaction with 91b in the absence of solvent gave, in addition to 92, the pyrido[2,l-/][l,2,4]triazine 93 and [l,3]oxazino[2,3-/][l,2,4]-triazine 94. In case of 91a pyridine and benzene derivatives were also formed in addition to 92 (Scheme 23). 

---