3- Amino-2-hydroxy-47/-pyrido

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. 

Protonation of pyrido[2,3-f ]pyrazine occurs normally without covalent hydration, although the 2-hydroxy derivative did show such behaviour (63JCS5737). The pyrido[3,4-f)]pyrazine parent base does show the phenomenon, although the exact structure of the covalent hydrate seemed to be in doubt between protonated (392) and (397). The issue was resolved in favour of the former by NMR (79JHC301, 75AG356). The 3-hydroxy derivative also shows hydration effects, as does the 7-amino cation (63JCS5166). 

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. 

Reaction of 2-amino-4/f-pyrido[l,2-n]pyrimidin-4-ones 143 with HNMei -HCl and paraformaldehyde in Dowtherm A afforded a mixture of 3-(A,A-dimethylamino)methyl derivatives 144 and bis-compounds 145 (93FES1225). Mannich reaction of 9-hydroxy-2-methyl-4//-pyri-dor],2-nlpyrimidin-4-one (146) yielded 8-aminomethyl derivatives 147 (94KFZ(10)23). 

Hydroxy-2-methyl-4//-pyrido[l,2-n]pyrimidin-4-one was prepared in the reaction of 2-amino-3-benzyloxypyridine and ethyl acetoacetate at 60 °C, then at 100 °C for 3 h in 22% yield (96MIP1). Reaction of 2-amino-3-hydroxypyridine and ethyl 2-methylacetoacetate in a 1 2 mixture of... 

Reaction of 2-amino-3-hydroxypyridine and cyclohexanone 433 in boiling AcOH yielded N, 1 -diphenyl-6-hydroxy-3-methyl-11 -0x0-1,2-dihydro-11 //-pyrido[2,l-Z)]quinazoline-2-carboxamide (434) (98MI2, 99USP5908840, 99USP5914327). 

Stereostructures of a co-crystal of (li )-l- 4-[(9aA)-perhydropyrido[l,2- ]pyrazin-2-yl]phenyl -2-phenyl-7-hydroxy-l, 2,3,4-tetrahydroisoquinoline with ERa-LBD301-553/C — S triple mutant <2005JME364> and iV-[2-(4-hydroxyphenyl)ethyl]-a-propyl-3-[(4-hydroxyphenyl)methyl]-l,4-dioxo-l,2,3,4,ll,l la-hexahydro-67/-pyrazino[l,2- ]isoquinoline-3-acetamide with fructose-1,6-biphosphatase <2003JBC51176> were determined by X-ray crystallography. The structure of a complex formed from 3-[( -methylphenyl)amino]-4-[(4-methylphenyl)imino]-4//-pyrido[l,2-tf]pyrazine with sodium bis(trimethylsilyl)amide and (norbornadiene)Mo(CO)4 in THF was characterized by single crystal X-ray diffraction <1995JPR38>. 

Mild acidic hydrolysis of amino nitrile 369 gave m-4,9a-/7-rra r-9-7/-9-benzyloxy-4-phenyl-3,4,9,9a-tetrahydro-17/,67/-pyrido[2,l-d[l,4]oxazin-l-one <1996TL4001>. (2A)-2-Cyano-l-[(lR)-2-hydroxy-l-phenylethyl]piperidin-6-one, on standing for 20 days in ethanol saturated with HC1 gas, afforded (4/ ,9aA)-4-phenylperhydropyrido[l,2-4[l,4]oxazine-l,6-dione, which was sometimes accompanied by the unstable (26 )-l-[(l/ )-2-hydroxy-l-phenylethyl]-... 

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>. 

Reaction of 3-formyM/7-pyrido[ 1,2- ]pyrimidin-l-ones with hydroxylamine O-sulfonic acid at 5 °C, then 50 °C yielded 3-nitriles <2003T4113>. Treatment of 2-hydroxy-3-(dimethylamono)methyF4//-pyrido[l,2- ]pyrimidin-4-one with Mel, then with KCN gave the 3-cyanomethyl derivative <2004MI215>. A condensation product was obtained from 5-amino-l-ethyl-6-hydroxy-l,3-dihydrobenzimidazol-2-one and 3-lbrmyl-2-hydroxyA//-pyndo[ 1,2- ]pynmidin-l-one <2002W002/38549>. l-(2-Aminopyrimidin-4-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-ones were prepared from l-(2-methylthiopyrimidin l-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-one by treatment with MCPBA, and then with aralkylamines <2005W005/070932>. 

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