Pyrido pyrimidines, reduction

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

Good yields of pyrido[2,3-d]pyrimidiries (37) were also oblaiiied by the action of formamide on o-amino nitriles (36). Reduction of 2-amino-4,6-dimethylnicotinitrilc yields the 3-aminomcthyl compound (38). Acylation to the 3-aoylaminomethyl derivative (39), followed by cyolization, by means of heat or phosphoryl chloride, yielded the dihydropyrido[2,3-d]pyrimidines (40). ... 

Structural proof has been offered by chlorination, thionation, and reduction to yield the pyrido[2,3-d]pyrimidine (74) which has been subjected to NMR analysis. ... 

The 3-amino group of 3,4-diamino-2//-pyrido[l,2-u]pyrimidin-2-ones 216, obtained from 3-nitroso derivatives by reduction with Na2S204 in 30% NH4OH at 70-80 °C, was acylated with acyl chlorides, and the acylated products 217 were cyclized to pyrido[2,l-Z)]purin-10-ones 218 by treatment with NaOMe (95JHC1725). 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

Selective reduction of the 7-oxo group in pyrido[23-synthetic approach to 5,10-dideazatetrahydrofolic acid <00H(53)1207>. Cycloaddition of pyrimido[4,5-c][l,2,5]oxadiazine 96 with 2,3-dihydrofuran affords a new synthesis of dimethyllumazine derivative 97 which undergoes a ring-opening reaction to give pyrazine derivative 98 <00JHC419>. 

Catalytic hydrogenation of the pyridine ring of 4-hydroxy-2-pyrrolidinopyrido[2,3- pyrimidine in the presence of H2/Pt02 in HCl gave 71. 2-(Pivaloylamino)-6-substituted pyrido[2,3-,7 pyrimidin-4(3//)-one gave the 5,6,7,8-tetra-hydro derivative 72 via similar catalytic reduction conditions in the presence of trifluoroacetic acid (TFA) at 800 psi hydrogen pressure for 40 h <1996WO9603406>. 

Within the following subsections the stability of the bicyclic ring system, plus the hydrogenation, reduction, dehydrogenation, oxidation, and quater-nization of the compounds are reviewed. This is followed by discussion of substitution reactions affecting the pyrido [ 1,2-a]pyrimidine ring, transformations of the side chains, and finally ring transformation reactions. 

According to Kobayashi et ul.,268 4-oxo- and 4-imino-4f f-pyrido[l,2-a]-pyrimidine-3-nitriles can be reduced to the 6,7,8,9-tetrahydro compounds with sodium borohydride. Reduction of the hydroiodide of 41 (R = H) with sodium borohydride or lithium aluminimum hydride, however, was unsuccessful.2... 

Attempts to reduce the quaternary salts of 4-oxo-4//-pyrido[l,2-a]-pyrimidines with sodium borohydride or lithium aluminum hydride remained unsuccessful.137 At the same time the 6,7,8,9-tetrahydro quaternary salts may readily be reduced with sodium borohydride to the 1-alkyl-l,6,7,8,9,9a-hexahydro derivatives.75-77,133 1481269 270 Sodium borohydride reduction of the 1,6- and l,7-dimethyl-3-carbamoyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidinium salts proceeds stereoselectively and yields the thermodynamically controlled product.271 The l-methyl-3-carbamoyl-4-oxo-l,6,7,8,9,9a-hexahydropyrido[l,2-a]pyrimidines were also prepared by the catalytic (Pd/C) hydrogenation of the 1,6,7,8-tetrahydro derivatives,270-272 but this reaction led to a diastereoisomeric mixture.271... 

Reduction of 3,4-dihydro-2//-pyrido[l,2-u]pyrimidine (135) with sodium in ethanol191 or by catalytic hydrogenation over platinum(IV) oxide afforded the perhydropyrido[l,2- ]pyrimidine (282).192... 

Hydrogenation of 2-oxo-3,4-dihydro-2//-pyrido[l,2-a]pyrimidines over platinum(IV) oxide in ethanol yielded the 2-oxoperhydro derivatives.200,217 The oxo group of the latter was eliminated by reduction with lithium aluminum hydride.192,342... 

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... 

Catalytic reduction of 2//-pyrido[l,2-a]pyrimidin-2-one 78 (R = Et, R1 = Ph) with hydrogen over Raney nickel in ethanol at ambient tempera-... 

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. 

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. 

Reduction of 3-nitroso derivative 329 by treatment with activated zinc dust in boiling acetic acid for 6 hours gave 3-amino derivative 330 [91IJC(B)839]. 2,3-Diamino-4//-pyrido[ 1,2-a]pyrimidin-4-one was pre-... 

Catalytic reduction of 7-(l-chloroalkyl)-8-chloro-9-[(dimethylamino-methylene)amino]-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-3-carboxylate 331 over 10% palladium-on-charcoal with hydrogen in acetic acid gave 7-alkyl-9-[(dimethylaminomethylene)amino]-4-oxo-4//-pyrido[l,2- ]pyrimidine-3-carboxylates 332 (91H1455). 

Reduction of 6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 341 and their quaternary salts 343 with sodium borohydride in water and methanol yielded the thermodynamically stable epimer 342 of 1,6,7,8,9,9a-hexahydro-4//-pyrido[l, 2-n]pyrimidin-4-ones (83SZP635100 85JOC2918),... 

Catalytic reduction of 3-phenyl-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a] pyrimidin-4-ones 350 over platinum oxide at 30°C under pressure of... 

The reaction of a molten mixture of 3,4-dihydro-2//-pyrido[ 1,2-a] pyrimidin-2-one 675 and phosphorous acid with phosphorus trichloride, followed by treatment of the reaction mixture with 2 N aqueous hydrochloric acid, afforded 3,4-dihydropyridopyrimidine-2,2-diphosphoric acid 676 in 38% yield (91GEP3930130). Catalytic reduction of diphosphonic acid 676 in water over platinum dioxide gave hexahydropyrido[l,2-a]pyrimi-dine-2,2-diphosphonic acid 677. 

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