Pyrrolo pyridine-5-ones

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... 

For example, pyrrolo[3,4-6]pyridine-5-ones (50) could be obtained by a four-component tandem process using an acryloyl chloride derivative (49) as an... 

The 1-arylpyrrole derivative (319) reacts normally with cyanide ions to give the 2-cyanomethylpyrrole (320), which subsequently undergoes an intramolecular cyclization to yield (321) (77FES339). The 2-cyanomethylpyrrole (322) also cyclizes, when treated with ammonia, to give the 17/-pyrrolo[3,2-c]pyridin-4-one (323) (80TL3135). 

Several names have been used in the chemical literature for pyrrolo[l,2-a]pyridine including pyrrocoline, pyrindole, pyrrodine and 8-pyrrolopyridine, but the one which is now used by Chemical Abstracts, and which will be used in this chapter, is indolizine. The numbering of the system is shown in formula (1). The denomination of aza derivatives follows the replacement nomenclature system, e.g. 1-azaindolizine, etc. It should be noted that Chemical Abstracts follows the systematic fusion nomenclature 1-azaindolizine, for instance, is imidazo[l,2-a]pyridine. The cyclazine nomenclature is treated in Section 3.08.9.1. 

Azalene salts 90 and 92 are obtained by quaternization of the corresponding heterocyclic bases with alkyl halides or tosylates. If the heterocyclic base contains several nitrogen atoms, alkylation can produce different quaternary salts. Quaternization, however, is surprisingly selective if certain conditions are met.205 Pyrrolo- and indolopyridines containing one pyridine-and one pyrrole-type nitrogen atom in their molecular lattice are (in aprotic solvents) almost exclusively alkylated at the nitrogen atom of the pyridine... 

A number of other five-membered ring nitrogen heterocycles have been prepared by cyclative cleavage. The illustrative examples (Fig. 4) depict the synthesis of pyrazolones,12 succinimides and phthalimides,13 pyrrolo[3,4-h] pyridines,14 2-aminoimidazolones,15 imidazo[4,5-fr]pyridin-2-ones,16 and l,2,4-triazoline-3,5-diones.17... 

B. Pyrrolo[3,2-c]pyridin-2-ones and Pyrido[3,4-6]pyrrolizidin-1-ones... 

Our interest in expanding the acylative pyrrole annulation approach to additional heterocyclic systems has led to an efficient synthesis of pyrrolo[3,2-c]pyridin-2-ones and pyrido[3,4-6]pyrrolizidin-l-ones starting from 4-chloro-N-benzyl-2(l//)-pyridinone and amino acid salts.811 Over the years pyrrolo[3,2-c]pyridines (5-azaindoles)41 have been of interest for applications as elements in new drug design, nucleotide analogues,42 and biochemical tools. However, available synthetic routes to multifunctionalized members from this class of heterocyclic structures are limited.41 43... 

Amino-l,5-naphthyridin-4 (1 //)-one (21) underwent diazotization to 3-diazo-nio-l,5-naphthyridin-4(1//)-one chloride (22) (substrate, Me2NCHO, 0°C, Me2CHCH2CH2ONO [, HCI/btOH [ 75%), which on irradiation gave 177-pyrrolo[3,2-b]pyridine-3-carboxylic acid hydrochloride (23) [substrate, AcOH, H20, 0°C, hv (arc lamp), h %].722... 

Amino-l,5-naphthyridin-4 (1 //)-one gave crude 3-diazonio-l,6-naphthyridin-4(l//)-one chloride (HC1, NaN02, 5°C, 12 h) and thence 3-diazonio-l,6-naphthyridin-4-olate (26) (NaHC03, Et20 70% overall) 726 subsequent irradiation caused ring contraction to pyrrolo [3,2-[Pg.133]

Amino-l,7-naphthyridin-4(l//)-one (10) underwent diazotization to give 4-oxo-3,4-dihydro-l,7-naphthyridin-3-ylidendiazonium chloride hydrochloride (11) (NaN02, HC1, 0°C 80%) and subsequent ring contraction on irradiation to afford pyrrolo[2,3-c]pyridine-3-carboxylic acid (12) (AcOH, H20, hv,... 

Reaction of l-(3,4-dimethoxybenzyl)-9-hydroxy-l,2,3,4-tetrahydro-8//-pyrido[l,2-a]pyrazin-8-one with 37% formaldehyde solution gave a tetracyclic tetrahydroprotoberberine analogue in a Mannich-type reaction (78AJC187). Reactions of 2,3,4,4a,5,6-hexahydro-l//-pyrazino[l,2-a]-quinolines with 1 W-pyrrolo[2,3-h]pyridine in the presence of 37% aqueous CH20 and AcONa in AcOH, and with 3-dimethylaminomethyl-l //-pyrrolo[2,3-h]pyridine afforded 3-[(l//-pyrrolo[2,3-h]pyridin-3-yl)methyl] derivatives (94MIP6 96USP5576319). 

The pyrrolopyridines contain one nitrogen heteroatom in the five-membered pyrrole ring and one nitrogen atom in the six-membered pyridine ring. A more common name is azaindoles, with 7-azaindole (l//-pyrrolo[2,3-6]pyridine (1)) being the most widely studied isomer of the series. Twelve isomers of pyrrolopyridines are listed in the Chemical Abstracts Ring Formula Index. Table 1 lists the pyrrolopyridines with their Chemical Abstracts Registry Numbers. The 1//-pyrrolopyridines (l)-(6) are the most frequently prepared, but some work has also been carried out on the isomers (7), (8), and (10). Isomers (8), (9), (11), and (12) are tautomeric structures which are considered later (see Section 7.06.4.4). 

The Mannich base derived from l//-pyrrolo[2,3- ]pyridine (71) can undergo a number of transformations and one of the most interesting is conversion to 7-azatryptophan (72) (Scheme 21), a nonnatural amino acid <68AHC(9)27>. 

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