Furo pyridines

The furo- and pyranobenzopyranones 114 and 115 are prepared by the reaction of 0-enolate of i(-keto lactone 113[132], The isoxazolc 117 is obtained by the oxidation of the oxime 116 of a, /3- or, d, 7-unsaturated ketones with PdCh and Na2C03 in dichloromethane[l 33], but the pyridine 118 is formed with PdCl2(Ph3P)2 and sodium phenoxide[134]. 

Furo[3,4-d]pyridazine-1,4-diones synthesis, 4, 985 Furopyridazines, 4, 984 Furo[2,3-6]pyridine, 3-amino-synthesis, 4, 977 Furo[2,3-6]pyridine, 4-methyl-synthesis, 4, 976 Furo[2,3-6]pyridine, 6-methyl-synthesis, 4, 976 Furo[2,3-6]pyridine, 5-nitro-synthesis, 4, 977 Furo[3,2-c]pyridine, 4-allyl-synthesis, 4, 982 Furopyri dines H NMR, 4, 983 physical data, 4, 983 properties, 4, 982 synthesis, 4, 974-982 UV spectroscopy, 4, 983 Furo[6]pyri dines HMO data, 4, 975 Furo[2,3-6]pyri dines synthesis, 4, 974-977 7, 512 Furo[3,2-6]pyri dines C NMR, 4, 982 synthesis, 4, 648, 981 Furo[c]pyri dines HMO data, 4, 976 Furo[2,3-c]pyri dines synthesis, 4, 977 Furo[3,2-c]pyri dines nitration, 4, 983 synthesis, 4, 978-981 Furo[3,4-c]pyri dines synthesis, 4, 982 Furo[3,2-c]pyridin-3-ols synthesis, 4, 980 Furo[2,3-6]pyridin-6-ones synthesis, 4, 976 Furo[3,4-c]pyridin-4-ones synthesis, 4, 982... 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

Merck has recently utilised a furo[2,3-b]pyridine core (554) as a bioisosteric replacement for the pyrazole scaffold of rimonabant (382) [328]. The same basic pharmacophore, that of two halo-substituted aryl groups and a third hydrophobic motif proximal to a hydrogen-bond acceptor, can be witnessed in the benzodioxole-based compounds, such as (555), disclosed by Roche [329]. 

Dipolar cycloaddition of 5-aminofuro[3,2-f]pyridinium tosylate 140 and the alkynyl ester 141 yields furo[3,2-f]pyrazolo[l,5- ]pyridine 142 in moderate yield (Equation 33) <1999CCC539>. 

Arnino-( l,6-di me thy I furo[3,2-< ])imidazo[4,5-Z pyridine (IFP), 496, is a known mutagen found in some cooked meats. It has been shown that IFP can be produced by heating of glutamine, creatine, and glucose <2000JFA1721>. 

In a similar way to the above, azidopropenoylfuro[3,2- ]pyrroles such as 27 can be thermolyzed in a mixture of diphenyl ether and tributylamine to give the 8-oxo-7,8-dihydropyrrolo[2, 3 4,5]furo[3,2-r]pyridines 28, again via the intermediate isocyanates. The lactam 28 can be chlorinated and reduced using standard methods (POCI3 then Zn/AcOH) to give the pyrrolo[2, 3 4,5]furo[3,2-r]pyridines 29 <1995M753> (Scheme 8). 

An alternative strategy for the synthesis of these tricyclic compounds involves the reaction of the azidoalkenyl-functionalized furo[3,2-A]pyrrole 30, which reacts with triphenylphosphine to give the corresponding iminophos-phoranes 31 these upon reaction with aryl isocyanates give the pyrrolo[2, 3 4,5]furo[3,2-r-]pyridines 32, via the corresponding carbodiimides which are not isolated < 1994H(37) 1695, 1992M807> (Scheme 9). 

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

As reported by Padwa and coworkers, exposing a suitable nitrofuran precursor to microwave irradiation in l-methyl-2-pyrrolidone (NMP) in the presence of 2,6-luti-dine catalyst provided l,4-dihydro-2H-benzo[4,5]furo[2,3-c]pyridin-3-one as the major product in 36% yield (Scheme 6.236) [419]. In contrast, under thermal conditions, removal of the tert-butyl group was observed as the major reaction pathway. 

On the basis of previously published data (235), concerning thermal rearrangement of 68 (R = Ph and mesityl) to furo[3,2-c]pyridine derivatives, reactions of mesitonitrile oxide and triphenylacetonitrile oxides were carried out (o-ChCehU, 170°C, 5 days) leading to compounds 72 (R = 2,4,6-Me3C6H2, PI13C) in 7% and 21% yields, respectively (Scheme 1.20) (234). 

Furo[2,3-b]pyridine-5-carboxylates (581) were obtained from 2-furyl-aminomethylenemalonates (580) by heating in Dowtherm A (66JHC202). 

The thermal ring closure of (V-(furo[2,3-6]pyridin-5-yl)aminomethy-lenemalonate (990) in boiling Dowtherm A for 12 min afforded furo[2, 3- ]-1,5-naphthyridinecarboxylate (991) in 77% yield (77MI6). 

A/-(Furo[3,2-i>]pyridin-2-yl)aminomethylenemalonates (1432) were stirred in a 1.2 N ethanolic solution of potassium hydroxide at ambient temperature for 1.5 hr, or in a 2 N ethanolic solution of sodium hydroxide under reflux for 6 hr, to give the 3-carboxylic acid (1433) in 33-61% yield (84G211). Solutions of N-(furopyridin-2-yI)aminomethylenemalonates (1432) in 2 N hydrochloric acid were refluxed for 2 hr to afford 2-aminofuro-pyridine-3-carboxylates (1434) in 55% and 82 % yields. When the 3-ethoxy-carbonyl derivative (1432, R = Et) was heated in a boiling aqueous ethanolic solution of potassium hydroxide for 2 hr, 2-pyridinylacetic acid (1435) was obtained in 47% yield. The treatment of the 4-nitrophenyl ester of 1432 (R = 4-N02Ph) with ethyl iodide in DMF in the presence of potassium carbonate gave the ethyl ester of 1432 (R = Et) in 91% yield (84G211). 

The total synthesis of the furo[3,2-a]carbazole alkaloid furostifoline is achieved in a highly convergent manner by successive formation of the car-bazole nucleus and annulation of the furan ring (Scheme 15). Electrophilic substitution of the arylamine 30 using the complex salt 6a provides complex 31. In this case, iodine in pyridine was the superior reagent for the oxidative cyclization to the carbazole 32. Finally, annulation of the furan ring by an Amberlyst 15-catalyzed cyclization affords furostifoline 33 [97]. 

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