Furo pyridine synthesis

Furo[3,4-d]pyridazine-l,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]pyridines HMO data, 4, 975 Furo[2,3-6]pyridines synthesis, 4, 974-977 7, 512 Furo[3,2-i>]pyridines 13C 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]pyridines 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>. 

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). 

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]. 

Disilylation of furo[3,4-r-]pyridine followed by dialkylation leads to the formation of a-disubstituted derivatives in good yields (61-70%). This methodology provides a key step in the synthesis of the pyridone alkaloid cerpegin, 54 <2004OL2925>. 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

Chloro-3-hydroxypyridine is a readily available starting point for the synthesis of furo[2,3- ]pyridines via iodina-tion followed by a palladium cross-coupling reaction with alkynes to afford alkynylpyridines, 107. Cyclization of compound 107 leads to furo[2,3- ]pyridine products <1998JME1357, 1998JOC7851 Similarly, reaction of 5-bromo-... 

Hydroxypicolinic acid is converted into hexahydrofuro[3,2- ]pyridine-3-one derivative 111 in a nine-step stereoselective synthesis <2004BMC5689>. 3-Iodo-4-prop-2-ynyloxypicolinanilides can be converted into furo[3,2-f]pyr-idine derivatives in good yields in the presence of tri- - butyltin hydride and AIBN <2004H(64)261>. 

Furo[3,4-7]pyridines can be prepared in a stereoselective synthesis involving a ruthenium-catalyzed asymmetric transfer hydrogenation reaction <2001TL1899>. The reaction proceeds with exceptionally high yield and ee (Equation 50). 

In the fused benzofuran series, the same method, applied to bromoacyl-o-hydroxycoumarins502,549 and bromoacyl-o-hydroxyxan-thones321,433,550 allows the synthesis of the corresponding oxo-dihydrofuro derivatives. The nitrogenated analogs of compounds 237 (2,3-dihydro-3-oxofuro[2,3-6] and -furo[3,2-c] pyridines) have also been obtained.551,552... 

While the synthesis of benzofuran derivatives from suitable furan derivatives has been comparatively little investigated, the synthesis of fused two-ring and three-ring compounds containing a pyridine nucleus from furan derivatives has been more successful furo[3,2-c]pyridines (345),752>753 2,3-dihydrofuro[2,3-a ]quinolines (from 4,5-dihydro-3-furoic acid),754 acrophyllin (346), and 7-hydroxydictamnine (347) (from ethyl 2-ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylate),755 are examples of compounds in this class which have been prepared. 

In another synthesis using a preformed pyridine derivative a cyanoacetic acid ester is condensed in a Guareschi-type reaction with an a-substituted /3-keto carboxylic acid ester and an amine to give a hydroxypyridone (18 Scheme 3). These compounds are suitable precursors for an acid catalyzed cyclization to furo[2,3-6]pyridine-6-ones (19). N-Substituted derivatives may also be prepared by this route (64AP754). The aqueous solutions of these furopyridines show an intensive blue fluorescence. 

Several routes are available for the preparation of furo[3,2-c]pyridine itself starting both from furan (Scheme 12) (71BSF1727, 71JHC57, 74BSF515) and from pyridine derivatives (Scheme 13) (71CR(C)(272)2197, 72BSF1442). The latter synthesis gives (8) in an overall yield of 12%. 

The construction of the furan ring in a Feist-Benary type reaction starting from 4-hydroxy-6-methylpyran-2-one (66) has also proved to be useful for the synthesis of furo[3,2-c]pyridines (Scheme 14) (75JHC461, cf. 71BSF4041). Quite recently the synthesis of the hitherto unknown furo[3,2-c]pyridin-3-ols has been described (79LA371). 4-Hydroxypyridine-3-carboxylates (e.g. 69), which are available from diketene and /3-aminocrotonic esters, react with a-halogenoketones in the presence of potassium carbonate to give compounds of type 70. 

The displacement of halogen with a copper(I) acetylide and subsequent or synchronous copper catalyzed addition of a neighboring nucleophilic substituent to the triple bond (equation 2) constitutes a versatile synthesis of heterocycles. This reaction has been utilized both for the synthesis of furo[3,2-c]pyridines (equation 3) and furo[3,2-6]pyridines (equation 4) (68JHC227, 72MI31700>. 

A one-step synthesis of furo[3,2-c]- and furo[3,2-6]-pyridines has been realized using a cycloaddition reaction of an alkynic compound with 3,5-dichloropyridine 1-oxide (Scheme 15) (75JA3227). Formation of (75) probably proceeds through a 1,2-dihydropyridine (73) with a subsequent 1,5-sigmatropic shift to (74) elimination of hydrogen chloride yields... 

Thieno[3,2-fc]pyridines are obtained in 49-87% yield (74JPR169). Application of the Friedlander reaction to 3-amino-2-formylthiophene gives (261) in reasonable yield (Scheme 78) (75ACS(B)224,75 ACS(B)233). As in the case of the synthesis of furo[3,2- >]pyridines (Section 3.17.2.1.1(i)(d), Scheme 17), it was unnecessary to isolate the o-aminocarbonyl compounds. 6-Substituted 7-hydroxythieno[3,2-6]pyridin-5(4/7)-ones (e.g. 295) can be prepared by base-catalyzed cyclization of the amides (294), which were obtained in high yields from readily available 3-amino-2-alkoxycarbonylthiophenes (293 Scheme 79) (80JCR(S)6) for... 

The preparation of selenolopyridazines is accomplished in the usual manner by condensation of diformylselenophenes with hydrazines. Both selenolo[2,3-cf]pyridazine (432) and selenolo[3,"4-tf]pyridazine (433) are obtained in this way (72BSF3453) as crystalline compounds with m.p. 158 and 153 °C, respectively. By strict analogy with the synthesis of boron containing furo- and thieno-pyridines (Sections 3.17.2.3.1, 3.17.3.3.1), boroxazoselenolo-pyridines (e.g. 434) and borazaroselenolopyridines (435,436) could be prepared by condensation of appropriately substituted formylselenophenoboronic acids and hydroxylamine or hydrazine <72IJS(A)(2)257>. 

Fischer indole synthesis, 157 fluorinated phosphine, 136 fuostifoline, 276 furo[2,3- ]pyridine, 281 furopyrimidine, 281, 393 furo[2,3-c]quinoline, 274 furylaniline, 272 furylboronic acid, 274 furylpyridine, 274 furylstannane, 277-9 2-furylzinc chloride, 271-4... 

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