Pyrano pyridines

Enamine (342 Ar = 3-methoxyphenyl) reacts with Nal in acetonitrile at 80 °C giving the pyrano-pyridine derivative (87) (40% yield) <89JCS(Pl)il77> and this represents an example of a transformation of the general type (295) -> (290). 

However, Hmited work has appeared with the carbon nucleophiles. Recently, an efficient tandem process has been developed that would allow the reaction of o-QM intermediates with carbon/nitrogen nucleophiles in situ to provide xanthene, naphtho(pyrano)pyridine/amidoalkyl naphthol derivatives under solvent-free and simple reaction conditions (Scheme 7.63). Xanthenes and benzoxanthenes are... 

An intramolecular variant of this cycloaddition process is combined with a Knoevenagel reaction in a total synthesis of the insectan leporin A, a pyrano[3,2-c]pyridine derivative <96JOC2839>. 

Thiazolonaphthyridinium salts 331 can be produced either by bromination of the 2-alkenylpyridine precursor, or by thermal cyclization of the 2-(bromoacetyl)pyridine (Scheme 81) <1997CL1203>, and reaction of the pyrano-pyrimidine 332 with o-aminothiophenol gives the benzothiazole-fused pyridopyrimidinedione 333 (Equation 118) <2003JCCS887>. 

INAC reactions have also led to enantioselective syntheses of key intermediates in the synthesis of antibiotic l 3-Methylcarbapenem (724), to optically pure derivatives of tetrahydropyrano[2,3] cyclohexane (725a) to novel terahydro-isoxazolo-fused pyrano 2,3-/ quinolines (725b) and to a novel heterocyclic system, isoxazolo[3,4-d]thieno[2,3-b]pyridine (Scheme 2.229) (221). 

The reaction of 2-imino-2/7-pyrano[2,3-c]pyridine-3-carboxamide with substituted 2-aminobenzophenones proceeds via ring opening and recyclization to give 3-(4-arylquinazolyn-2-yl)-277-pyrano[2,3-( ]pyridin-2-ones (Scheme 9) <2005SG1641>. 

Pyrano-fused heterocycles, namely pyrano[3,2-f]quinoline-2,5(6//)-diones, pyrano[3,2-f]benzopyran-2,5(6//)-dione, and pyrano[3,2-f]pyridine-2,5(67T)-diones, have been efficiently prepared by the condensation of 4-hydroxy-2-(l//)-quinolines, 4-hydroxycoumarin, or 4-hydroxy-(17/)-pyridone with a-acetyl-y-butyrolactone or the sodium salt of a-formyl-y-butyro-lactone in the presence of ammonium acetate <1999JHC467>. 

Epicorazine A (8S,9R,9aS,10aS)-9-Ethenyl-8-(P-D-glucopyranosyloxy)- 2,3,9,9a,10,10a-hexahydro-5H,8H-pyrano[4,3-d]thiazolo- [3,2-a]pyridine-5-one Xylostosidine... 

Hydroxylamine converts pyran-2-ones into pyridine IV-oxides by attack at the 1,2-bond for example, the pyran-2-one (278), obtained by heating 3-acetyI-4-hydroxy-6-methyl-pyran-2-one (dehydroacetic acid) and DMF dimethyl acetal in xylene, reacts with two moles of hydroxylamine under mild conditions to give the pyrano[2,3-6]pyridine JV-oxide (279) (77JHC931). Hydrazine converts pyran-2-ones into l-amino-2-pyridones (78JHC759). 

When 3-(4-j -tolyloxybut-2-ynyloxy)[l]benzopyran-2-one 1 was heated under reflux in carefully purified chlorobenzene, the exclusive product, formed in 92% yield, was 1 -(p-tolyloxymethyl)pyrano[2,3-c][l]benzopyran-5(3i/)-one 2. The compound 2 was also the exclusive product when either xylene or ethylbenzene was used as solvent. However, when 1 was heated under reflux in chlorobenzene containing a catalytic amount of AIBN, 2 was obtained in 20% yield together with 80% of 2-methyl-l-(p-tolyloxymethyl)furo[2,3-c] [l]benzopyran-4-one 3. The compound 3 was the exclusive product when PEG-600, IV.lV-dimethylaniline, pyridine or ethylbenzene containing a catalytic amount of p-TsOH was used as solvent, the yields being 90,90, 80 and 90% respectively. 

Phenyl-5//-pyrano [4,3-/ ] pyridin-5-one (140) with ethanolamine gave 6-(2-hydroxyethyl)-7-phenyl-l,6-naphthyridin-5(6//)-one (141) (reactants, MeOH, reflux, 3 h 91%).902... 

A-(3,5-Bis(trifluoromethyl)benzyl]-8-oxo-5-p-totyl-8//-pyrano[3,4-h]pyridine-6-carboxamide (47, X=0) and ethanolamine gave iV-[3,5-bis(trifluoromethyl) benzyl -7-(2-hydroxyethyl)-8-oxo-5-/ -totyl-7,8-dihydro-l,7-naphthyridine-6-carboxamide (47, X = NCH2CH2OH) (reactants, MeOH, THF, 20°C, 16 h then to dryness solid, diazabicycloundecane, MeCN, PhMe, reflux, 1 h 70%) analogs likewise.243 944 cf 556 1252... 

Methyl 1-met hy I-3-oxo-3,4-dihydro-1 //-pyrano 3,4-r pyridine-5-carboxylate (39) with methanolic ammonia gave 5-(l-hydroxyethyl)-2,7-naphthyridine-l,3(2ff,7fl)-dione (40) (20°C 78%)206... 

Phenyl-1 //-pyrano[3,4-c pyridin-l-one (41) gave 2-(2-hydroxyethyl)-3-phenyl-2,7-naphthyridin-1 (277)-one (42) (H2NCH2CH2OH, MeOH, reflux 82%).902... 

Dimethylaminovinyl)-5-oxo-2,7-diphenyl-5//-pyrano 4,3-/ pyridine-3-car-bonitrile (43) with propylamine gave 8-oxo-l-phenacyl-3-phenyl-7-propyl-2,7-naphthyridine-4-carbonitrile (44) (PrNH2, pyridine, reflux 58%).987... 

Heterocycles (167) and (168) react with sodium hydride yielding the pyrano[2,3-/>]pyridines (130) <92JOC1930> and 1,8-naphthyridine derivatives (111) <92JMC518> respectively a related synthesis of tetrahydropyrano[2,3-6]pyridines has been reported <71JCS(B)279>. Under acidic conditions, the diester (169) affords heterocycle (170) (44% yield) <93H(35)93>. The sulfone (171) reacts with LDA giving an intermediate (172) which cyclizes yielding the sulfone (173) (Scheme 1) <84JOC5l36>. 

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