Pyrido pyrimi

A similar delocalization of charge which stabilizes the relevant intermediate occurs in 4-mercaptopteridine and pyrido[4,3-d]-P3Timidine-4(3 r)-thione. Both these compounds are cleaved under similar conditions. Such a delocalization is not possible with either pyrido[3,2-d]- or pyrido[3,4-d]pyTimidine-4(3 r)-thione and although the latter compound could not be prepared, the pjTido[3,2-d]pyrimi-dine was quite stable under these conditions. 

Conformations of 4-oxo-l,6,7,8,9,9n-hexahydro-4//-pyrido[l,2-n]pyrimi-dine-3-carboxylates and -3-carboxamides were studied by semiempirical quantum chemical calculations at the AMI level (97H(45)2175). While 1-methyl-9n-unsubstituted derivatives adopt a cA-fused conformation, 9a-ethoxy-1-methyl derivatives adopt a trans-fu ed one to avoid a serious non-bonding interaction between 9n-ethoxy and 1-methyl groups, which would be present in an alternative cA-fused conformation. 

Reaction of l-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimi-din-l-ium-2-olate (148) with tetracyanoethylene afforded 3-substituted derivative 149 (95H(40)681). 

The hydroxy group of ethyl 9-hydroxy-4-oxo-4//-pyrido[l,2-u]pyrimi-dine-3-carboxylate was O-alkylated with 2-chloromethyl-4-isopropyl-l,... 

A 14 1 mixture of ( )- and (Z)-phenylhydrazones 249 and 250 was obtained from 2-[A-(cyclohex-2-en-l-yl)]-3-formyl-4/7-pyrido[l, 2-n]pyrimi-din-4-one 248 with PhNHNH2. Pentacyclic compound 251 was obtained from both ( )- and (Z)-phenylhydrazones 249 and 250 by heating in boiling EtOH (96T901). 

Dicyano-2,4,8-triphenyl-7-phenylsulfonyl-6/f-pyrido[], 2-a]pyrimi-dine-6-thione was obtained in the reaction of 6-amino-1-benzoyl-5-cyano-4-phenyl-3-phenylsulfonylpyridin-2(]//)-one and benzylidenemalononitrile in the presence of piperidine in boiling dioxane for 4h in 59% yields (98M1049). 

Reaction of 2-aminopyridine and 6-chloro-1,3-dipropyl-l//,3//-pyrimi-dine-2,4-dione in THE in the presence of NaH at room temperature overnight gave a mixture of 4-[A-(propylaminocarbonyl)-A-propylamino]-2//-pyrido[l,2-n]pyrimidin-2-one (349) and 6-(2-pyridylamine)-l,3-dipropyl-l//,3//-pyrimidine-2,4-dione (350, R = H) (94JHC81). Only the non-cyclized product 350 (R = Cl) was obtained from 5-chloro-2-aminopyridine. 

Cyclocondensation of 2-amino-6-bromopyridine and 4-chloroacetoace-tate in PPA at 100 °C for 4h afforded a mixture of 2-chloromethyl-, 2-bromomethyl-6-bromo-, and 2-chloromethyl-, 2-bromomethyl-6-chloro-4//-pyrido[l,2-n]pyrimidin-4-ones in 84% yield (99JHC1065). The pyrido-[l, 2-a]pyrimidin-4-ones were separated by preparative reversed phase HPFC. The pure 2-bromomethyl-6-bromo-4//-pyrido[l,2-n]pyrimi-din-4-one was prepared from 2-amino-6-bromopyridine with ethyl 4-bromoacetoacetate in 63% yield. Reaction of 2-aminomethylpyridines and ethyl 4-chloroacetoacetate in PPA at 110°C gave 2-chloromethyl-4//-pyrido[l,2-n]pyrimidin-4-ones (95FFS69, 01H(55)535). 

Cyclocondensation 2- [2-cyano-2-(2-pyridyl)ethenyl]amino -3-(dimethy-lamino)acrylates and 2-aminopyridines in boiling AcOH for 1-1.5 h afforded 3- [2-cyano-2-(2-pyridyl)ethenyl]amino -4//-pyrido[l,2-n]pyrimi-din-4-ones in low yields (01H(55)705, 01JHC869). 

Several syntheses of annulated uracils of biological value were recently reported. The key reaction was a microwave-assisted one-pot [4 -i- 2] cycloaddition of oxazino[4,5-d]-, pyrano-[2,3-d]-, pyrido[2,3-dj- and pyrimido[4,5-djpyrimidines, in the sohd state [134] and under solvent-free conditions [135]. The synthetic approach was based on the reaction of NJ -di-methyl-5-formylbarbituric acid 208 with maleimide in the sohd state for 5 min under microwave irradiation at 120 °C to give the pyrano[2,3-d]pyrimi-dine derivative 209 in 90% yield (Scheme 76). The reaction of 208 with phenyl isocyanate under microwave irradiation in the absence of solvent... 

Methylthio-47/-pyrido[l,2-tf]pyrimidin l-one was prepared by FVT of 2-methylthio-4-oxo l/7-pyrido[l,2- ]pyrimi-dine-3-carboxylic acid at 650°C at 8 x 10 smbar for 4h <1999J(P2)1087>. Heating 9-ethoxycarbonylmethylene4-oxo-... 

Reactions of stable N-substituted iminopropadienones with 2-methylaminopyridine in CH2C12 yielded 1 -methyl-2-(iV-substituted imino)-l,2-dihydropyrido[l,2- ]pyridinium-5-ium-4-olates <2002JOC2619>. Reactions of N-substituted iminopropadienones with 2-aminopyridines provided 2-(substituted aruino)-l//-pyrido[ 1, Z-a pyrimi-din-4-ones, which were accompanied by a small amount of isomeric 4-(substituted arnino)-2/7-pyrido[ 1,2- ]pynrnidin-2-ones. In refluxing toluene, a larger amount of the 2-oxo isomers formed. In the case of 2-amino-3-methylpyridine and... 

AJC287>. From a complex reaction mixture of BuCH(COCl)2 and 2- 4-[(4-hydroxy-3-carboxyphenyl)hydrazi-no]phenylsulfonylamino pyridine at elevated temperature, tf yr/r >-(3-butyl-2-hydroxy-4-oxo-4//-pyrido[l,2-tf]pyrimi-din-3-ylium)hydroxide was isolated <2001MI53>. Reaction of 2-aminopyridines and diethyl alkylidenemalonates at 175 °C yielded 3-(2,2-disubstituted vinyl)-2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-ones from the initially formed... 

Cyclocondensation of ethyl 2-aminonicotinate in presence of HC(OEt)3 and various primary amines gave 22 3-substituted pyrido[2,3-,7]pyrimidin-4(377)-ones 371 <1995PHA719>. Fourteen 3,5,7-triarylpyrido[2,3-r7]pyrimi-dine-2,4(l/7,37/)-diones 372 have been prepared from the reaction of either 2-amino-3-cyano-4,6-diarylpyridines or the 3-carboxamido products of alcoholic KOH hydrolysis, with aryl isocyanates better yields were obtained from the amides <1995IJB740>. 4-Aminopyrido[2,3- pyrimidin-5(8//)-one 158 was synthesized by treatment of 2-amino-3-cyano-4-methoxypyridine with trimethylsilyl iodide to give the corresponding pyridin-4(177)-one, which was refluxed with formamidine acetate in ethoxyethanol to effect the cyclization <2000JME3704>. 

Addition of arylisothiocyanates to the active methylene compound 538 led to the formation of pyrido[2,3- / pyrimi-dines 540 and 541, resulting from the initial addition to form the pyridine intermediates 539 followed by a second addition to give the products (Equation 44) <1993JHC887>. 

Die Synthese von 2-Aryl-9-oxo-9H-[Pg.614]

Okamoto et a/.156 cyclized the dinitriles (86 R = CN, R2 = H) by heating in 15° hydrochloric acid to obtain pyrido[l,2-a]pyrimidine-3-carboxylic acids (89 R2 = H). 2-Aminopyridinium chloride and ethoxymethylene-malononitrile at 110CC yielded 3-cyano-4-imino-4H-pyrido[l,2-a]pyrimi-dine (87 R1 = R2 = H, X = NH) and compound 91. Under similar conditions, 2-amino-3-methylpyridine gave a noncyclized product of type 91. 

Kurasawa and Takada transformed the 2-oxo-2H-pyrido[l,2-u]pyrimi-dine (30) with phosphoryl chloride-dimethylformamide to the pyrido-[l,2-a]pyrimidine (201) and reacted the latter with methylhydrazine to obtain 4°, of the pyrido[l,2-a] pyrimidine (202) and 78% of the pyridazino-[3,4-b]quinoxaline(203 R = Me, R2 = NMeNH2). Reaction with hydrazine gave the pyridazino[3,4-b]quinoxaline (203 R = H, R2 = OEt).26-27... 

The 2-chloro substituent may be exchanged for various nucleophiles. The 2-alkoxy derivatives were formed with alkali metal alkoxides,98,1 12,255,273 the 2-amino derivatives were formed with ammonia and amines,79,98,255, 260.283,285,286 t]ie 2-hydrazino derivatives were formed with hydrazine,98,255,283,287 and the 2-thiocyanatb derivatives were formed with alkali metal thiocyanates.283 2,3-Dichloro-4-oxo-4//-pyrido[l,2-fl]pyrimi-dine in phenol reacts with gaseous ammonia to yield a mixture of the 2-phenoxy and 2-amino derivatives, whereas with sodium hydroxide, the 2-phenoxy compound is obtained.255... 

As part of their study on aza-transfer reactions, Tisler and co-work-ers289 290 reacted 2-hydrazino-4-oxo-4//-pyrido[l,2-u]pyrimidine with various diazo derivatives and obtained 2-azido- and 2-amino-4-oxo-4/f-pyrido[l,2-u]pyrimidines. From 2-azido-4-oxo-4/f-pyrido[l,2-u]pyrimi-dines various derivatives of 2-(l,2,3-triazol-l-yl)-4-oxo-4//-pyrido[1.2- ]-pyrimidine (221) were prepared by reaction with acetylene,287 1,3-dioxo compounds,166 ordiethylamine.291 For further ring transformation reactions of the 2-azido-4-oxo-4//-pyrido[l,2- ]pyrimidine (102), see Section lll.C.lO. 

Chloro-3-formyl-4-oxo-4/Y-pyrido[l,2-a]pyrimidine was transformed with hydrazine and ethylenediamine, respectively, to the tricyclic compounds 22898 and 229.285 Treatment of 2,3-diamino-4-oxo-4//-pyrido[l,2-a]pyrim-idines with sodium nitrite in aqueous acetic acid afforded the pyrido [1,2-a]-r-triazolo[4,5-d]pyrimidines (230).31 Reaction of the pyrido[l,2-a]pyrimi-... 

The hydroxy group of 3-hydroxy-3,4-dihydro-2//-pyrido[l,2-a]pyrimi-dine was acylated with acid chlorides in pyridine341 and exchanged for chlorine by treatment with thionyl chloride.190 The resulting chloro derivative (131 mp = 46.5-47 C) was transformed on standing to a compound containing ionic chlorine (mp = 193 C). The structure of the latter remained unclarified.190... 

The 6-oxopyrido[l,2-a] pyrimidine remained unchanged on catalytic hydrogenation (PtOz, Raney nickel) but decomposed when treated with lithium aluminum hydride.255 The oxo group of the 6-oxo-9a-phenylpyrido-[l,2-a]pyrimidine (179) was reduced with lithium aluminum hydride.230,232 On reduction with sodium borohydride, the 2-phenylpyrido[l,2-a]pyrimi-dine (184) gave the piperidine derivative (182).240,241 The 6-oxoperhydro-pyrido[ 1,2-a]pyrimidines were acylated at the N-l atom with dichloroacetyl chloride.343... 

As discussed in Sections II,B and C, the 4-oxo-4//-pyrido[l,2- ]pyrimi-dines have often been incorrectly described as 2-oxo-2/f-pyrido[l,2-a]-pyrimidines34-38-92 or as 1,8-naphthyridines.33-81128 These three types of compounds can be distinguished on the basis of their UV, NMR, and mass spectra. 

Tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-one was prepared by the decarboxylation of 6,7,8,9-tetrahydro-4-oxo-47/-pyrido[ 1,2-a]pyrimi-dine-3-carboxylic acid in 85% phosphoric acid at 160-170°C for 6 hours (85ACH305). Decarboxylation of 9-anilino-4-oxotetrahydropyridopy-rimidine-3-carboxylic acid derivatives 422 occurred in refluxing 2% aqueous sodium hydroxide under argon to give 3-unsubstituted derivatives 423 [85JCS(P1)1015],... 

---