3- Nitro-9-hydroxy-4//-pyrido

Dinitro-9-hydroxy-4//-pyrido[l,2-a]pyrimidin-4-one was obtained when 3-nitro-9-hydroxy-4//-pyrido[ 1,2-a]pyrimidin-4-one was treated with a mixture of concentrated sulfuric and concentrated nitric acids at 0°C for 1 hour [90JCR(S)308]. 

Heating 9-hydroxy-2-methyl-8-nitro-4//-pyrido[ 1,2-a]pyrimidin-4-one 326 in dimethylformamide in the presence of hydrazine hydrate and Raney nickel at 50°C afforded 8-amino derivative 327 (92KGS1660). 8-Amino derivative 327 was also prepared from 8-phenylazo derivative 328. 

Chemical reduction [with aqueous titanium(III) chloride in dilute acetic acid] or catalytic reduction (in the presence of 10% palladium-on-charcoal by transfer hydrogenation from cyclohexene or with hydrogen) of 3-nitro-4//-pyrido[l,2-a]pyrimidin-4-ones 176 (R = H, 8-Me, 8-OMe, 7-C1) gave 3-amino-4//-pyrido[l,2-a]pyrimidin-4-ones [90JCR(S)308]. Chemical and catalytic reduction of 3,8-dinitro-9-hydroxy-4//-pyrido[l,2-a]pyrimidin-4-one yielded an unstable product. 

Nitro groups have been reduced to amino groups, whilst amino groups in the 3- and 6-positions of pyrido[2,3-f ]pyrazines and in the 5-position of the [3,4-f ] isomers have been hydrolyzed to the corresponding hydroxy derivatives with alkali. Protected amino groups have been liberated by hydrolysis or reduction in deazapteridine syntheses. 

Diorganotin(IV) complexes with 4//-pyrido[l,2-n]pyrimidin-4-ones 109 (96MI4), complexes of 2-methyl- and 2-methyl-8-nitro-9-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-ones with Ag(I), Cu(II), Ni(II), Co(II), and Mn(II) ions (00MI23), 2,4-dimethyl-9-hydroxypyrido[l, 2-n]pyrimidinium perchlorate and its complexes with prasedynium, neodymium, samarium and europium (00MI24) were characterized by UV spectroscopy. 

Diorganotin(IV) complexes (109) were prepared from 4/f-pyrido[l,2-a]pyrimidin-4-ones with Me2SnCl2 and Ph2SnCl2 in dry CHCI3 (96MI4). Different complexes of 2-methyl-9-hydroxy-4//-pyrido[l, 2-n]pyrimidin-4-one and its 8-nitro derivative were prepared with Cu(I)Cl, Cu(II)Cl2, Ni(II)Cl2, Co(II)Cl2, Mn(II)Cl2, and Ag(I)N03 m EtOH (00MI23). Complexes of 2,4-dimethyl-9-hydroxypyrido[l,2-n]pyrimidinium salt were obtained with Pr(III), Nd(III), Sm(III), and Eu(III) ions in acetone (00MI24). 

R = Ar) and cyclized tricyclic compound 240 (R = Ar) was obtained when 2-bromoacetophenones were reacted with 8-hydroxyquinolin-2(l//)-one under the above conditions. Presence of a 4-methoxy substituent shifted the equilibrium to the ring-opened product 241 (R = 4-MeOPh), while that of 4-nitro group gave only cyclized product 240 (R = N02). Similarly, mixtures of ring-opened and 2,3,6,7-tetrahydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one derivatives were formed in the reaction of 8-hydroxy-l,2,3,4-tetrahydroquinolin-2-one and halomethyl ketones (00HCA349). 

Nitration of 2-substituted 4/7-pyrido[l,2- ]pyrimidin-4-ones with 99% HN03 in cone. H2S04 gave 3-nitro derivatives <2000BMC751, 2001H(55)535>. Mannich reaction of 2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-one afforded... 

This reaction was extended to prepare 7-nitro- and 9-nitro derivatives of pyrido[l,2-a]pyrimidinone 119 (R = N02, R1 = H R = H, R1 = N02) when the appropriate starting material 118 was heated in boiling dichloro-methane in the presence of triethylamine or when it was stirred in aqueous sodium hydroxide at 20°C (92AJC1825) or treated with sodium azide in aqueous tetrahydrofuran (92AJC2037). Semiempirical molecular orbital calculations (AMI) indicated that the 2-hydroxy-4-oxo tautomeric forms 119 are more stable than the alternative 4-hydroxy-2-oxo tautomeric forms. 

R = 3-Me) gave only pyrido[ 1,2-a]pyrimidine 150 (R = 9-Me), and the 3-hydroxy derivative 149 (R = 3-OH) afforded 30% of pyrido[l,2-a]pyrimidine 150 (R = 9-OH) and 10% of pyridylpyrrolinone 151 (R = 3-OH). From the 6-substituted succinates 149 (R = 6-Me, 4,6-diMe, 6-OH, 6-NHAc) only pyridylpyrrolinones 151 (R = 6-Me, 4,6-diMe, 6-OH, 6-NHAc) were obtained. In the latter two cases the steric properties of substituents 3 and 6 might also play a role during ring closure. The 3,5-dichloro-, 3- and 5-nitro, and 5-carbamoyl derivatives of succinate 149 did not give any cyclized product under basic conditions [84JCS(P1)1799]. 

When 7-nitro-2-hydroxy-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-3-carboxyl-ate 119 (R = N02, R1 = H) was boiled in an alcohol for 15 minutes, it was partly converted to diesters 315 (R = COOalkyl) (92AJC1825). If the 7-nitro derivative was heated in hexachloroacetone or in dimethyl sufoxide, malonamate 315 (R = H) was formed, presumably due to traces of adventitious water. 

Reduction of nitro derivatives of 2-hydroxy-4-oxo-pyrido[l, 2-a] pyrimidine-3-carboxylates 119 (R = N02, R1 = H R = H, R = N02) could be carried out by zinc and acetic acid to yield the appropriate unsaturated amino derivative (92AJC1825). Catalytic reduction at 1 atm gave only partially reduced products. 

Hydroxy-2-methyl-4//-pyrido[ 1,2-a]pyrimidin-4-one 365 gave 8-sub-stituted derivatives in a reaction with different electrophilic reagents (Scheme 28) (92KGS1660). Nitration gave 8-nitro-9-hydroxy-2-methyl-pyridopyrimidin-4-one 326. Reaction with iodine afforded 8-iodo-... 

Phenyl-2//-pyrido 2,3-<7 [l,3]oxazine-2,4(l//)-dione (64) with diethyl malo-nate gave ethyl 4-hydroxy-2-oxo-l-phenyl-l,2-dihydro-l,8-naphthyridine-3-carboxylate (65) (reactants, NaH, 150°C 85%) 453,407 the same substrate (64) with ethyl nitroacetate gave 4-hydroxy-3-nitro-l-phenyl-1,8-naphthyr-idin-2(lfl)-one (66) (NaH/MeCONMe2, 100°C 77%).1191... 

Reaction of 3,4-dihydro-7-nitro-2//-l, 4-benzoxazine-4,5-dicarboxylic anhydride with diethyl malonate in the presence of 60% NaH in N, yV-dimethylacetamide at 120°C afforded ethyl 7-hydroxy-9-nitro-5-oxo-2,3-dihydro-5//-pyrido[l,2,3-cte]-l,4-benzoxazine-6-carboxylate (93MIP4). 9-Chloro-2,3-dihydro-7-hydroxy-6-(jV,./V-disubstituted thiocarbamoyl)-5//-pyrido[l,2,3-de]-l,4-benzoxazin-5-ones were prepared from 7-chloro-3,4-dihydro-2//-1,4-benzoxazine-4,5-dicarboxylic anhydride with 3-(N,N-disubstituted amino)-3-thioxopropionates in the presence of 60% NaH in yV,yV-dimethylacetamide (95MIP5). 

Diamino-6-hydroxypyrimidine condenses with nitromalonaldehyde in presence of alkali to give 2-amino-4-hydroxy-6-nitropyrido[2,3-d]pyrimi-dine (100) (75%).92 In a similar reaction 2,4-dioxo-l-hydroxy-6-nitro-lf/,3//-pyrido[2,3-d]pyrimidine is formed (101) [Eq. (32)].93... 

Pyridazine 4-Amino-5-nitro-3-phenyl- E9a, 617 (H -> NH2) Pyrido[2,3-d pyrimidin 6-Cyan-4-hydroxy-7-methoxy-2-methyl-E9c, 93 [2-NH2 —3-(CO—... 

Phthalazine l,4-Dihydroxy-5(or 6)-dimethylamino- E9a, 752 (subst. Phthalanhydrid/N2H4) lH-PyrazoI 5-Methyl-5-nitro-4-phenyl-4,5-dihydro- X/l, 426 Pyrido[2,3-d]pyrimidin 4-Hydroxy-2-oxo-l-propyl-1,2-dihydro- E9c,... 

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