Pyrido pyrimidine-2,4-diones, 6-aryl

Semiempirical PM 3 MO calculations were performed on eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones and on their dimers (00JPO213). In all of the calculated structures the aromatic ring is almost perpendicular to the plane of the pyrido[l,2-c]pyrimidin-l,3-dione fragment, which is in accordance with the X-ray data for 4-(4-methylphenyl) derivative. 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

Cyclocondensation of a-aryl-2-pyridylacetamides and 2-(3,4-dihydroiso-quinolin-l-yl)acetamide with Et2C03 in the presence of NaOEt in boiling EtOH afforded 4-aryl-2,3-dihydro-l//-pyrido[l,2-c]pyrimidine-l,3-diones (99JHC389) and 6,7-dihydro-4//-pyrimido[6,1 -a]isoquinoline-2,4-dione (98MIP15), respectively. 

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>. 

Dipolar cycloaddition of anhydro pyrido[2,l-b][l,3]thiazinium hydroxides (128) with aryl isocyanates and dimethyl acetylenedicarboxylate gave pyrido[l,2]pyrimidines (129) and quinolizine-l,2-dicarboxylates (130), respectively (76CB3668). 1,4-Dipolar cycloaddition of pyrido[2,l-h][l,3]thi-azinium betaine (131, R = Me) with 1-diethylamino-l-propyne afforded cycloadduct 132, from which quinolizin-4-one 133 formed by a rapid cheletropic extrusion of carbonyl sulfide (93TL5405 95T6651). 1,4-Dipolar cycloaddition of anhydro 4-hydroxyl-2-oxo-6,7,8,9-tetrahydro-2//-pyrido-[2,l-b][l,3]thiazinium hydroxides (131) and 4-phenyl-l,2,4-triazoline-3,5-dione yielded 135 via 134 [94H(39)219 95H(41)1631] and 136 (95T6651). 

The structures of 4-aryl-2,3-dihydro-lH-pyrido[l,2-c]pyrimidine-l,3-diones hydrochlorides 50 were characterized by solid-state 13C CPMAS NMR spectroscopy (08JST325). 

Cyano-2,3-dihydro-lH-pyrido[l,2-c]pyrimidin-l- and -3-ones were N-alkylated with Mel in the presence of K2CC>3 in DMF (05MI1). 4-Aryl-2,3-dihydro-lH-pyrido[l,2-c]pyrimidine-l, 3-diones were N(2)-alkylated with 1,4-dibromobutane in the presence of K2C03 in boiling acetone for 2 h in 57-95% yields (06EJM125). 

Piperidyl)indoles were N-alkylated with 4-aryl-2-(4-bromobutyl)-2,3-dihydro-lH-pyrido[l,2-c]pyrimidinel,3-diones in the presence of K2C03 and a catalytic amount of KI in boiling MeCN for 4-5 h in 50-90% yields (09EJC1710). The bromo atom of 2-(4-bromobutyl)-4-aryl-2,3-dihydro-lH-pyrido[l,2-c]pyrimidine-l,3-diones was replaced by 4-(het)arylpiperazino... 

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 with acyclic precursors in a one-pot reaction, 2-amino-2-[(4,6-dimethylpyrimidin-2-yl)methylene]pentane-2,4-dione (29) reacts with two molecules of aryl isocyanate to yield the corresponding 3-aryl-7-(arylamino)-4-methyl-8-(4,6-dimethylpyrimidin-2-yl)pyrido[2,3-rfl-pyrimidine-2,5(3//,8 tf)-dione (30).404 40 5... 

Other typical C3 components are 2-aryl-3-(dimethylamino)acryladehyde.257 3-(methylamino)-bul-3-en-2-one, A-unsubstituted 2-(aminomethylene)cycloalkanones,258 or l-phenyl-3-pipe-ridinoprop-2-en-l-one,259 all of which can be regarded as vinylogous amides. With 4-amino-uracils in dilute acetic acid at reflux temperature, pyrido[2,3-d]pyrimidine-2,4(1 f/,3//)-diones 26 are obtained. According to the position of substituenls in Ihese cases, the amino group of the uracil reacts with the /5-vinyl carbon, followed by cyclization through electrophilic attack of the aldehyde or ketone carbonyl.257,259... 

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