3-Ethyl-3- piperidine-2,6-dione

DV-7028 (3- 2-[4-(4-fluorobenzoyl)piperidin-Tyl]ethyl -6,7,8,9-tetrahydro-27/-pyrido[l,2- ][l,3,5]triazine-2,4(3//)-dione maleate, 150 (Figure 4) a 5-HT2A-receptor antagonist, exhibited cardiovascular effects in a rat model C1998MI266, 1996MI325, 1998MI259>. 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

Reactions of 3,3-diethyl-3,4-dihydro-2//-pyrimido 2,l-a]isoquinoline-2,4-dione (65) with ethanol in the presence of hydrogen chloride and piperidine at 60-70°C afforded ethyl lV-(l-isoquinolyl)-2,2-diethylmalonamate (66) and l-(2-ethylbutyramido)isoquinoline (67), respectively (69YZ649). 

Methyl 3-ethoxycarbonylaminothiophene-2-carboxylates 211a derived from o-aminoesters 189 (Y = Me) and ethyl chloroformate were heated at 130-135°C with ethanolamine to give 3-(2-hydroxyethyl)thienopyrimidine-2)l//),4(3//)-diones 212 (89CPB1197, 89CPB2091). Several 3-[3-ethyl(4-substituted piperidine or piperazine)thienopyrimidine-2(l//),4-diones 214... 

Reactions of 3-substituted 2-(lV-phenylaminomethyl)piperazines with a slight excess of ethyl 2-chloroacetate under reflux afforded mixtures of 9-substituted 2-phenylperhydropyrido[l,2-a]pyrazin-3- and -4-ones, which could be separated by column chromatography [72JCS(P2)1374], When 2-[(3-trifluoromethylphenyl)aminomethyl]piperidine was heated with optically active ethyl 2-chloropropionate (87MIP1 91TA231), or lactic acid ethyl ester methanesulphonate (91TA231), the product was a C-9a epimeric mixture of 2-(3-trifluoromethylphenyl)-4-methylperhydropyrido[l,2-fl]-pyrazin-3-ones. The reaction between yV-methyl-2-piperidine-carboxamide and hydroxymaleic anhydride in pyridine resulted in 2,3-dimethyl-3-hydroxyperhydropyrido[l,2-a]pyrazine-l,4-dione (74CB2804). 

The parent system (99) has been obtained by lithium aluminum hydride reduction of perhydro-imidazo[l,5-a]pyridine-l,3-dione (from ethyl 2-piperidine carboxylate and cyanic acid) and by ring closure of 2-aminomethylpiperidine with formaldehyde. 3-Substituted derivatives have also been described. The 3-phenyl- and 3-/-butyl derivatives (but not the propyl and benzyl derivatives) show ring-chain tautomerism (70JHC355). 

Perhydropyrido[l,2-c]pyrimidine-l,3-diones were prepared in the reaction of alkyl 2-piperidineacetate with ethyl urethane in diethyl ether in the presence of sodium (56CB1642), by heating with KOCN in hydrochloric acid (59CB637 64JMC146). l-Thioxoperhydropyrido[l,2-c] pyrimidin-3-one was obtained when ethyl 2-piperidine acetate was reacted with KSCN in acidified ethanol (59CB637). Reaction of methyl 2-piperidyl acetate with aryl isocyanates yielded 2-arylperhydropyrido[l,2-c]pyrimidine-... 

Ethyl-3-methyl glutarimide 4-Ethyl-4-methyl piperidine-2,6-dione B.P. (1968) U.S.P. (XVII) Int. P, Ind. P. ... 

Liping et al. [68] reported the iodine-catalyzed one-pot multicomponent reaction of ethyl trifluoroacetoacetate, indan-l,3-dione, ammonium acetate, and aromatic aldehyde which gave ethyl-6 -hydroxy-l,3-dioxo-2, 4 -diaryl-6 -(trifluoromethyl)-l,3-dihydrospiro[indene-2,3 -piperidine]-5 -carboxylate derivatives 50 as the major product and 2-trifluoromethyl-2,3,4,5-tetrahydro-l/f-indeno[l,2-b]pyridine derivative 51 as the minor product (Scheme 10.33). 

---