Pyrrolopyridines substitution

Pyrrolopyridines substituted at the 2-position of dipyridodiazepinones have been prepared for study as nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase <1997JME2430>. Compound 141, synthesized from pyrrolo[2,3-, ]pyridine as a starting material, has emerged as a novel inhibitor of HIV-1. Compound 141 acts by interfering with the initial viral entry process <2003JME4236>. 

Pyrrolopyridines substituted on the pyrrole nitrogen are subject to attack by permanganate ion, resulting in ring-opened products as shown in Scheme 25 (43CB128,50JCS2952). 

Pyrrolo[2,3-3]- and -[3,2- ]-pyridines can be substituted at the 2-position of N-protected rings via a palladium-catalyzed reaction (Pd(OAc)2) using lithium chloride and sodium acetate in DMF <2000TL919>. This reaction, which proceeds in moderate to good yields (60-92%), is especially useful for preparing 2-aryl- or 2-heteroaryl-substituted pyrrolopyridines. 

Partially hydrogenated pyrrolopyridines have been prepared through a sequence that includes an alkynyl-substituted pyrimidine ring. An initial intramolecular inverse electron demand Diels-Alder reaction is followed by a cycloreversion to form a dihydropyrrolopyridine. The pyrimidine ring is generated in four steps starting with an alkynyl carboxylic acid (Scheme 7) <2004JOC9215>. 

A microwave-assisted synthesis of several isomeric pyrrolopyridines ([2,3-3], [2,3-c], [3,2-3], and [3,2-r ]) has been reported starting from aminohalopyridines <2005S2571>. Intramolecular palladium-catalyzed Heck reactions leading to substituted pyrrolo[3,2-3]pyridines from ketones and aminopyridines have been described <2003JME4702>. 

MO calculations for 5192,213-216 and l217 and their conjugate acids indicate high jr-electron density at position 3 in common with pyrrolopyridines,7 this is found to be the predominant position for electrophilic substitution. 

Halogenation of pyrazolo[4,3-c]pyridines has not been reported, but all other isomers, as with pyrrolopyridines, undergo substitution mainly in the 3-position. 

Bromine smoothly substitutes C-3 of the pyrrolopyridines, in contrast to pyrrole and indole which react violently to give polybromo derivatives (see Section 3.02.2.4.7). For example, pyrrolo[2,3-6]pyridine (4) reacts with bromine in chloroform at 0°C to give the... 

An ab initio study of some methyl derivatives of pyrrolopyridines was also conducted. In addition to confirming some of the findings of the unsubstituted pyrrolopyridine study, this study also found that basicity increases with methyl substitution <82T3693,88JA2699). 

Transformations involving dihydro derivatives of the pyrrolopyridines have been reported as useful methods for achieving substitution at positions of the ring that do not readily react directly. For example, substituents have been introduced into compound (59), which can be subsequently dehydrogenated to the pyrrolopyridine derivative. Scheme 17 shows that from transformations beginning with the nitration of compound (59), 5-nitro-l//-pyrrolo[2,3-6]pyridine (64) and 5-amino-1 /7-pyrrolo[2,3-6]pyridine (65) can be obtained <59JA743>. 

---