Pyrrolo pyridine, 1,3-dimethyl

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

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). 

DaB bei dieser Cycloadditionsreaktion auch das Aiken nicht beliebig gewahlt werden kann, zeigt die Reaktion des Iminium-ylids mit l-Methyl-l,2,3,6-tetrahydro-pyridin, die nur in maBiger Ausbeute zu einem Gemisch von 2,5-Dimethyl-octahydro-(pyrrolo[3,4-c]pyridiny und 1,4-Dimethyl-piperazin fiihrt2 das letztere Produkt bildet sich auch in an-deren Fallen durch Cyclodimerisierung des Iminium-ylids. 

Pyrrolopyridines are quaternized at the pyridine nitrogen by methyl iodide (often at room temperature). Sodium hydroxide treatment of the methiodide of pyrrolo[2,3-6]pyridine gives a stable free base which reacts with a second molecule of methyl iodide, this time at the pyrrole nitrogen (Scheme 4). The resonance stabilization of the free base is shown by its stability towards boiling 20% sodium hydroxide, which rapidly hydrolyzes l-methyl-2-pyridoneimine (55JA6554). The same procedure with S-carboline leads to the 1,5-dimethyl quaternary salt (19) which on pyrolysis yields the 5-methyl derivative (20 Scheme 5) (60CJC2152). 

The pyrimidothiazine (204) extrudes sulfur at 130 °C to give the pyrrolopyrimidine (205 Scheme 64) (71TL4185). (-Butoxybis(dimethylamino)methane (BBDM) is a substitute for dimethylformamide dimethyl acetal. It is used to prepare the pyrimido[5,4-c]pyridazine (206). Hydrogenation gives the pyrrolopyrimidine (207 78% Scheme 65) (78JOC2536). By a similar reduction, pyrido[3,2-c]pyridazine is converted into pyrrolo[3,2-6]pyridine (80RCR428). 

Other products from pyridine and its 3- and 4-methyl and 3,5-dimethyl derivatives and MP are cyclazines (e.g., 100),291 which are probably formed from indolizines of type 97 by further reaction with MP and subsequent aromatization. This type of reaction has been achieved by heating appropriate indolizines with DMAD293 or MP in the presence of palladized charcoal, and the direction of the addition, as shown below, has been established in several instances.294 Heating MP with diethyl-2-pyridylmethylene malonate gave the pyrrolo[2,l,5- /]indolizine corresponding to 100, no trace of the expected indolizine intermediate (cf. 97) being observed.292... 

Reaction of the aldehyde (86) with methyl azidoacetate in the presence of sodium methoxide was found to proceed smoothly to give azide (255), which upon thermolysis in boiling toluene gave dimethyl l-methyl-7//-furo[3,2-6 4,5-6 ]dipyrrole-2,6-dicarboxylate (256). Compound (255) reacted with triphenylphosphine in dry dichloromethane to give the iminophosphorane (257), which with phenyl or 3-chlorophenyl isocyanate in dry toluene under reflux gave the substituted pyrrolo-[2,3 4,5]furo[3,2-c]pyridines (258) or (259) via carbodiimides, which were not isolated (Scheme 16). The compounds (8i), (84), and (87) undergo similar reactions <92M807,94H(37)1695>. 

The synthesis of 5,7-dimethyl-l//-pyrrolo[2,3-c]pyridine (85) has been carried out starting with 4-chloro-2,6-dimethyl-3-nitropyridine (86) according to Scheme 35 <84H(22)1347>. 

Dimethyl-8-ethoxycarbonyl-l, 8-dihydro- E9d, 364 (7-R-1H-[Pg.1029]

Bei Diaminenderen Amino-Gruppen sich in ihrer Basizitat unterscheiden, sind selek-tive Umsetzungen moglich. So wird z.B. 7-Amino-6-methyl-2,3-dihydro-lH-(pyrrolo-[3,4-cJ-pyridin) mit einem Aquivalent Formaldehyd am starker basischen sek. cyelischen Stickstoff zum 7-Amino-2,6-dimethyl-2,3-dihydro-1H-(pyrrolo-[3,4-c)-pyridin) (80% d.Th.) methyliert2. Analog verhalt sich Butanal ... 

A solution of 5-bromo-4,6-dimethyl-2,3 -dihydro-lH-pyrrolo[2,3-b]pyridine (1.1 g, 4.56 mmol) in a mixture of 10 mL 37% aqueous HCHO and 10 mL of 90% HCO3H was refluxed for 18 h. On cooling, the mixture was reduced in vacuo and basified with 15 M aqueous KOH. The suspension was cooled in an ice bath, and the precipitate filtered, washed with water, and dried. Chromatography (3 1 hexanes EtOAc) gave the product as white needles. 

Diaza-compounds. Phenacyl bromide reacts with 2-aminopyridine 1-oxide to yield 2-phenylimidazo[l,2-a]pyridin-3-ol (769) another derivative of this ring system, compound (771), is produced by the action of diphenylketen on the sulphilimide (770), dimethyl sulphide being eliminated.(6-Methyl-2-pyri-dyl)acetyl azide (772) forms the dihydroimidazo[3,4-a]pyridinone (773) on heating." Whereas l-methylpyrrole-2-aldehyde and other heterocyclic aldehydes react with tosylmethyl isocyanide to give oxazoles, e.g. (774), pyrrole-2-aldehyde affords the 6-azaindolizine (775). The action of potassium amide on the derivative (776) of 3-bromopyridine furnishes the pyrrolo[3,4-c]pyridine (777) by cyclization of an intermediate pyridyne." ... 

Cl5H1eN 03, 2,5-Diethyl-7-(1-methyl-2-imidazolyl)-1H-pyrrolo[3,4-c]-pyridin-1,3,6 2H,5H)-trione, 41B, 331 Cl5H1yBrN204, Dimethyl 6-bromo-1-(1-pyrrolidinyl)-3H-pyrroline-2,3-dicarboxylate, 40B, 251... 

There is continuing interest in the synthetic potential of the (4-1-2) cycloadducts of polyazabenzenes. For example, 1,2,4-triazines bearing dialkylamino-or alkoxy-groups at the 3- and/or 5-positions react with ynamines to yield cyclo-adducts of type (343 X = NMca or OMe), which by loss of nitrogen give substituted pyridines (344), However, 1,2,4-triazines containing two or three dialkylamino-groups react only with electron-deficient dienophiles, e.g. dimethyl acetylenedicarboxylate. In addition to the anticipated dimethyl 2,6-bis-di-methylaminopyridine-3,4-dicarboxylate, pyrrolo[2,l-/][l,2,4]triazine (345) is formed, albeit in minor amounts. Anomalous behaviour is shown by 3,5-bis-dimethylamino-6-methoxy-1,2,4-triazine, which with the acetylene-... 

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