Pyrido pyrimidine-2,5-diones amination

For the preparation of pyrido[2,3-d]pvrimidinc-2,4(l//,3//)-diones 28, an adaption of the Doebner-Miller quinaldine synthesis (cf. Houben-Weyl, Vol. E7a, p 363), can be used. The orientation of addition of oc,/5-unsaturated carbonyl compounds to pyrimidin-6-amines is governed by the attack of C5 of the pyrimidinamine at the carbon /5 to the carbonyl function.219 Besides pyrimidine-2,4,6-triamine,149 263 aminouracils are used as partners for the base-catalyzed reaction with a,/5-unsaturated ketones.148,219 264,570,571 Without the final oxidation step, which occurs mostly by air, the dihydro compounds are produced.265 Examples are the Michael additions of 4,4-dimethyl-l-phenylpent-l-en-3-one266 or of 1,3-diphenylprop-2-en-l-one264 to 6-amino-l,3-dimethylpyrimidine-2,4(l//,37T)-dione, which are followed by ring closure to give the corresponding pyrido[2,3-d]pyrimidme-2,4(l//,3//)-diones or their dihydro derivatives. 

Examples for the alkaline hydrolysis of acylated 2-amino groups are the formation of 6-bromo-l-methylpyrido[2,3-i/]pyrimidine-2,4(l//,3//)-dione (35) from 6-bromo-l-methyl-2-(pivaloylamino)pyrido[2,3-[Pg.151]

Ar-[(Ar,Ar-Dimethylamino)methylene]pyrido[2,3-c/]pyrimidin-4-amine 3-oxide (6) plays a central role as an educt for 3-(3-pyridyl)-l,2,4-oxadiazoles. Thus, it has been treated with carbon nucleophiles such as the anions of diethyl malonate, ethyl cyanoacetate, or pentanc-2,4-dione.417 After addition across the 2,3-bond, ring opening of the pyrimidine moiety with simultaneous 1,2,4-oxadiazole ring formation occurs. Evidently, the five-membered ring is formed easily through participation of the [(dimethylamino)methylene]amino and TV-oxide functions. 

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>. 

Mesoionic pyrido[2,l- >][1,3]oxazines (54) afforded 4-oxo-4//-pyrido[l,2-a]pyrimidin-l-iumolates (55) and 4//-quinolizin-4-one (56) with phenyl iso(thio)cyanates [78LA1655 79CB1585 82ZN(B)222] and dimethyl acetylenedicarboxylate (79CB1585), respectively. Reaction of 2-cyano-3-methyl-lH,6//-pyridol[l,2-a][3,l]benzoxazine-l,6-dione with ammonium acetate and hydroxylamine, hydrazines, primary aliphatic or aromatic amines, and (thio)ureas gave 5-unsubstituted and 5-substituted 2-cyano-3-methyl-l//,6H-pyrido[l,2-a]quinazoline-l,6-diones (93CCC1953). 

A mixture of the appropriate pyrido[3,4-fi/]pyrimidine-l,4(2/7,3/T)-dione (1 g), POC l3 (15 mL, 164 mmol) and V.Y-dimethylaniline (1.5 mL, 119mmol) was heated at 100-110CC for 3-4 h. The excess POCI, was evaporated in vacuo and the residue poured into ice-water. The resulting crystals were filtered to give crude 7-aryl-l,4-dichloropyrido[3,4-fi/]pyridazine, which was refluxed with the cyclic amine (6mL) for 1 —3 h. After removal of the excess amine, H20 was added to the residue. The filtration and recrystallization of the resulting crystals gave the product. 

Starting from 2-chloronicotinonitrile, N1 -substituted pyrido[2,3-t/]pyrimidine-2,4(177,3//)-diones can be synthesized without isolation of the intermediates. The 2-amino group is introduced by the SN reaction of the chlorine substituent with an amine, followed by acid-catalyzed hydrolysis of the nitrile group and final cyclization with urea."... 

The combination of two moles of a pyridinamine and two moles of carbon dioxide at elevated temperatures and high pressure yields 3-(2-pyridyl)pyrido[2,3-t/]pyrimidine-2,4(l f/,3/7)-diones.137 Thus, pyridin-2-amine and carbon dioxide at 8500 atm and 200 "C gave 3-(2-pyridyl)-pyrido[2,3-<2]pyrimidine-2,4(l //,3/7)-dione (R = H). 

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