C-Aminomethylenation

Shaw concluded that hydrogenation of 3-alkyl-4-aminomethylene isoxazol-5-ones (184) in the presence of palladium catalyst resulted in the saturation of either the endocyclic double carbon-nitrogen bond or the exocyclic double C—C bond with the retention of the heterocyclic nitrogen-oxygen bond. Recent data reported by Kochetkov et al. on the properties, and in particular on hydrogenation, of isoxazolid-5-ones - indicate, however, that Shaw had probably ob-... 

R = H, R =Br, R" =Et) was prepared by cyclization of aroylacetate 314 (R = H, R =Br, r2 = H, X = F) (OOMIPIO). 9,10-Difluoro-3(5)-methyl-7-oxo-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylic acid and its racemic form were prepared in the reaction of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-2-ethoxymethyleneacetate and (R)- or (i ,5)-2-aminopropanol and subsequent hydrolysis of the ring closed tricyclic esters (98MI45). Cyclization of ethyl 2-(2,3-difluoro-5-iodobenzoyl)-2-[A-(2-hydroxyethyl)aminomethylene]acetate 315 in the presence of K2CO3 in DMF at 95 °C for 3.5 h yielded 9-iodo-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylate (01MIP2). 

Scheme 21 Formation of 5-(aminomethylene)cyclopentenones 101 and 2-(r-aminoalkenyl)-cyclopentenones 102 by formal [2+2+1] cycloadditions. Conditions A THF, 50-55 °C. B THF/ MeCN (9/1), 65 °C [82,83]. For further details see Table 4...

Oxo-3,4-dihydro-2-quinoxalinecarboxamide (23) gave 3-chloro-A -(dimethyl-aminomethylene)-2-quinoxalinecarboxamide (24) (POCI3, Me2NCHO, 20°C 70°C, 8h 65%)7 ... 

Oxo-3,4-dihydro-2-quinoxalinecarboxamide (117) gave 3-chloro-/V-dimethyl aminomethylene-2-quinoxalinecarboxamide (118) (POCl3, Me2NCHO, 0°C > 70°C, 8 h 65%).748... 

Coronaridine subtype alkaloids are widely spread in Tabernaemontana. The iboga skeleton is particularly susceptible to oxidation at aminomethylenes C-3 and C-5 and at benzylic C-6. Very often, the fundamental compounds are accompanied by the oxidation products at these positions. 

The reaction of pyrido[2,3-c/]pyrimidine-3-oxide (415) and diethyl malonate in the presence of sodium ethylate in ethanol at 0°C for 10 min led to the formation of Af-[3-(l,2,4-oxadiazol-3-yl)-2-pyridyl]aminomethylene-malonate (416) in 73% yield, but at ambient temperature for 1.5 hr, the product was diethyl N-(3-cyano-2-pyridyl)aminomethylenemaIonate in 61% yield (83JOC4132). 

Cyclization did not occur with (sulfamidophenyl)aminomethylene-malonates (565) (containing R=6-chloropyridazin-3-yl, 3-methylisoxa-zol-5-yl or 2-methylthiazol-5-yl, R1 = H) at 250°C because of the thermal instability of the aminomethylenemalonates (76FES237). At a lower temperature in Dowtherm A or in diethyl phthalate at 170-180°C, they remained unaltered. 

The cyclization of diethyl A[-(4-methylcinnolin-8-yl)aminomethylene-malonate in diphenyl ether at 245°C for 20 min gave pyrido[3,2-/i]cinnoline-8-carboxylate (610) in 31% yield (51JOC1414). 

The thermal ring closure of AKl,3-benzodithiol-5-yl)aminomethylene-malonate (860) in Dowtherm A at 253-258°C led to a 7.3 1 mixture of 1,3-dithiolo[4,5-g]quinolinecarboxylate (861) and l,3-dithiolo[4,5-/]quinoli-necarboxylate (862) in 81% yield (86M1339). The cyclization of diethyl N-(3,4-dimethylthiophenyl)aminomethylenemalonate under similar conditions afforded only ethyl 6,7-dimethylthio-4-hydroxyquinoline-3-carbox-ylate. 

Cyclopropyl-1,4-dihydro-1,8-naphthyridine-3-carboxylate (1025) was prepared in 43-48% yields by the cyclization of jV-cyclopropyl-M-[6-(4 - ethoxycarbonyl -1 - piperazinyl) -5- fluoro -2-pyridyl ] aminomethylene -malonate (111) in acetic acid by the action of concentrated sulfuric acid at 55-60°C for 1 hr (85EUP153163, 85EUP153828, 85EUP159174 86EUP172651 88EUP265230). 

The cyclization of diethyl /V-(5-phenyl-3-pyrazolyl)aminomethylene-malonate by heating in the melt at 180°C gave 2-phenylpyrazolo[l,5-a]py-rimidine-6-carboxylate (1102, R = 2-Ph) (81FES441). 

The pyrolysis of isopropylidene N-(a-methylbenzyl)aminomethylene-malonate (1233) at 600°C and 1(T2 torrgave 3-(l-phenylethylidene)amino-acrylaldehyde (1234) in 46% yield [84JCS(P1)2129]. 

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