5-Phenyl-2- 2-<pyrido -ethyl

Ethyl propiolate reacted with (416) in boiling benzene giving ethyl l-oxo-2-phenyl-liT-pyrido[2,l-6]benzothiazole-4-carboxylate in 83% yield, and no trace of the other possible isomer was found. 

Reaction of 2-aminopyridine with ethyl 2-cyano-3-ethoxy-3-methyl-, -3-ethyl-, -3-phenylacrylates and ethyl 2-ethoxycarbonyl-3-ethoxy-3-methyl-, -3-phenylacrylates in boiling xylene yielded 2-substituted 4/f-pyrido[l,2-u]pyrimidine-3-carbonitriles and -3-carboxylates (99MI7). Similar reactions of 2-aminopyridine with 2-cyano-3-ethoxyacrylonitrile and its 3-methyl, 3-ethyl, -3-phenyl derivatives in boiling MeCN afforded 4-imino-4//-pyrido[l,2-u]-pyrimidine-3-carbonitrile and its 2-substituted derivatives. 

A sulfoxide was obtained by oxidation of 8-[(4-trifluoromethylmercapto-phenyl)methoxy] derivative 358 with 36% H2O2 in AcOH (98MIP7) and by oxidation of l-[2-(4-thiomorfolin-l-yl)acetyl]-7-(3-methoxyphenyl)-A-methyl-A- [3,5-bis(trifluoromethyl)phenyl]ethyl -5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/ ]quinoxaline-6-carboxamide with 3-chloroperbenzoic acid (01MIP12). A 7-[(4-fluorophenylsulfonyl)methyl] derivative was obtained by oxidation of a 7-[(4-fluorophenylsulfanyl)methyl]perhydropyrido[l,2-u] prazine with 3-chloroperbenzoic acid in CHCI3 (01EUP1074257). 

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>. 

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>. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

Al-Jallo and Al-Biaty24 prepared 4-phenyl-2-oxo-2H-pyrido[l,2-c<]-pyrimidines from 2-aminopyridines and ethyl phenylpropiolate. When the reactions were carried out in deuterium oxide, the 3-deuterated derivatives were obtained. 2-Amino-5-nitropyridine failed to react. 

Mandereau et a/.193 prepared the alcohol (133) by reducing ethyl 2-pyridylaminopropionate with lithium aluminum hydride. The alcohol was then transformed with thionyl chloride to the chloride (134) and cyclized with an equimolar amount of sodium hydroxide in methanol to the pyrido-[l,2-u]pyrimidine (135). The 4-phenyl and 4-(p-tolyl) analogs were prepared in a similar fashion. The 4-(p-methoxyphenyl) derivative could only be obtained by heating the alcohol of type 133 in acetic anhydride. The pyrido[l,2-a]pyrimidine-4-carboxylicacid (137) was prepared by ring transformation of the pyridylpyrrolidinone (136) with methanolic sodium hydroxide.193... 

Methyl-7-phenyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-one was prepared in the reaction of 2-amino-5-phenyl-3,4,5,6-tetrahydropyri-dine and ethyl acetoacetate either in refluxing xylene or in boiling alcoholic sodium ethylate (83JHC393). 

A 1,4-dipolar cycloaddition between tetrahydropyrido[l,2-a]pyrimidi-none 114 (R = Me) and 4-methyl-l, 2,4-triazoline-3,5-dione 666gave stable adduct 667 in acetonitrile or in acetic acid at room temperature for 1 hour (Scheme 44) (85CB4567). When ethyl cyanoformate was used as dienophile in boiling toluene for 20 hours, ethyl 3-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a]pyrimidine-2-carboxylate 669 was obtained (86CB1445). Pyrido[l,2-a]pyrimidine-2-carboxylate 669 was formed from the initial adduct 668 by elimination of phenyl isocyanate. Reaction of tetrahydropyr-ido[l,2-a]pyrimidinone 114 (R = Me) with l-(diethylamino)-l-propyne in... 

Catalytic hydrogenation of 2-(2,4-difluorophenoxy)-5- 2-vinylphenyl and 2-[(lE)-prop-l-enyl)phenyl] -6H-pyrido[l,2-fc]pyridazin-6-ones over Pd/ C in EtOAc yielded 5-(2-ethyl- and 2-propylphenyl) derivatives (07USA2007/0129372). 

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