Pyrimidin-4-ones, 5-ethoxycarbonyl

H-Selenazolo[3,2-a]pyrimidin-5-ones, ethoxycarbonyl-synthesis, 5, 142 6, 359 7H-Selenazolo[3,2-a]pyrimidin-7-ones synthesis, 5, 142 6, 345 Selenirenes, 6, 349 Selenium... 

Pyrazino[2,3-d]pyrimidine — see Pteridines 4//-Pyrazino[l,2-a]pyrimidin-4-one, 3-ethoxycarbonyl-synthesis, 3, 366... 

Alkylation of diethyl acetamidomalonate with the bromomethyl-pyrimidine (88) yielded 6-acetamido-6-ethoxycarbonyl-6,6-dihydro-2-methylthiopyrido[2,3-d]pyrimidin-7(8//)-one (90), via the cyclization of the intermediate ester (89). 

Cyclization of methyl 2-[2-benzoyl-2-ethoxycarbonyl-l-vinyl)amino]-3-[(4-methyl-2-pyridyl)amino]acrylate (311) afforded the 3-amino-8-methyl-4//-pyrido[l,2-n]pyrimidin-4-one derivative 312 (97JHC1511). 

The inverse electron demand reactions of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine and 5-aminopyrazoles to provide a one-step synthesis of pyrazolo[3,4-. 

The 1,2,4-triazole ring of 2,3,5,6,7,8-hexahydro-l,2,4-triazolo[4,3-a] pyrimidin-3-ones (60) was constructed by cyclocondensation of the 1-ethoxycarbonyl-2-methylthio-l,4,5,6-tetrahydropyrimidine 58 with hydrazine (86JPR331), arylhydrazines [86H(24)93, 86KGS1350 88JPR753], or thiosemicarbazide (87KGS1540) (Scheme 24). 

Dowtherm gives 3-ethoxycarbonyl-4//-pyrazino[l,2-a]pyrimidin-4-one (275) in good yield. Ethyl phenylcyanoacetate also condenses with the starting pyrazine to give 2-hydroxy-4-imino-3-phenyl-4H-pyrazino[l,2-a]pyrimidine (276). Condensation of (274) with ethyl phenylmalonate gives zwitterion (277) (68JMC1045). 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

The 9-benzoyl- and 9-[(ethoxycarbonyl)carbonyl]tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones also exhibit predominantly the 1,6,7,8-tetrahydro tautomeric forms in solution [85JHC593 89JCS(P2)1613]. 

Reaction of 3-formyl derivative 375 with ethyl bromoacetate in boiling ethanol in the presence of sodium ethylate yielded 2-[(ethoxycarbonyl) methoxy]-3-formylpyrido[ 1,2-a]pyrimidin-4-one 376 [91 IJC(B)839]. The... 

Reaction of 3-formyl-4//-pyrido[l,2-a]pyrimidin-4-ones 409 with [(ethoxycarbonyl)methylene]triphenylphosphorane in a Wittig reaction in dimethylformamide at ambient temperature for 10 hours gave 3-trans-acrylates 410 (92JHC559). The 3-formyl group of 3,9-diformyl-l,6,7,8,-tetrahydro and 3-formyl-9-phenylhydrazono-6,7,8,9-tetrahydro-4//-pyr-ido[l,2-a]pyrimidines was transformed to a trans-acrylate side chain in a Wittig reaction with [(ethoxycarbonyl)methylene]triphenylphosphorane in dimethyl sulfoxide at room temperature for 24 hours (84JMC1253). 

Vielsmeier-Haack formylation of /-substituted 2-phenylamino-4/7-pyrido[ 1,2-a]pyrimidin-4-ones 470 with a mixture of phosphoryl chloride and dimethylformamide at 95°C for 90 minutes gave a near 1 1 mixture of pyrido[r,2 I,2]pyrimido[4,5-6]quinazolin-12-one 472and -12,13 dione 473 in 23-37% and 22-41% yields, respectively (87JHC329). Compounds 472 and 473 probably formed by the disproportionation of the tetracyclic hydroxyl derivatives 471. If the substituent (R) of 470 was the ethoxycar-bonyl group, only N-ethoxycarbonyl derivative 475 could be obtained (92JHC25). No tetracyclic derivative 472 and/or 473 (R = COOEt) was formed. 

Cyclocondenzation of 2-pyridylacetonitrile and ethoxycarbonyl isothiocyanate in MeCN gave 4-cyano-l-oxo-2,3-dihydro-lH-pyrido[l,2-c]pyrimi-dine-3-thione in 18% yield (08MI2). 6-Endo-trig cyclization of anion, formed from 4-methylpyrimidine by LDA in THF at —78 °C, with methyl 3-propynoate provided 8-methyl-6H-pyrido[2,l-c]pyrimidin-6-one in 47% yield (06TL5063). 

The starting material is produced by reacting 6-amino-2-methylthiopyrimidine with ethoxymethylene malonic acid diethyl ester. That intermediate is thermally treated in diphenyl ether to give 6-ethoxycarbonyl-2-methylthio-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine. The ethoxy group is hydrolyzed off with sodium hydroxide and one nitrogen is ethylated with diethyl sulfate to give the starting material. These are the same initial steps as used in the pipemidic acid syntheses earlier in this volume. 

Ethyl derivatives of (185) and ethyl propiolate afford 2-ethyl-7i7-1,3,4-selenadiazolo[3,2-a]pyrimidin-7-one (189) and 2- or 3-ethoxycarbonyl-5H-selenan-zolo[3,2-a]pyrimidin-5-one (190). The reaction of (185) and DAMD afford the bicyclic compounds (191 Scheme 83) (75JHC675). 

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