2,3,4,4a, 5,6-Hexahydro-17/-pyrido

Perhydropyrido[l,2-6]pyridazine was prepared from perhydropyrido [l,2-fc]pyridazin-2-one by reduction with LAH (65MI1, 65URP170506 66KGS91 78JA4012), and from 4,4a,5,6,7,8-hexahydro-3//-pyrido[l,2-b] pyridazine by catalytic reduction over Pt02 in acetic acid (68YZ216). Re-... 

Methylation of 4,4a,5,6,7,8-hexahydro-3//-pyrido[l,2-c]pyrimidin-3-one (108, R = H) with methylmagnesium chloride in the presence of CU2I2 or Cu2Br2 gave l-methylperhydropyrido[l,2-c]pyrimidin-3-one (109) (84EUP104647 85JMC1285). Reduction of 108 either over Pd/C... 

Cyclocondensation of l-methylthio-4,4a,5,6,7,8-hexahydro-3//-pyrido [l,2-c]pyrimidine (139) with anthranilic acids (71JMC878 72USP3631046 74USP3772230 75USP3868372) or with ethyl 5-amino-3-methylisothiazole-4-carboxylate [76IJC(B)391] afforded the tetracyclic derivatives 140 and 141, respectively. 

Microwave irradiation of 3-(fur-2 -ylmethylene)-l,5-dimethyl-2,6-diphenylpiperidin-4-one 609 with urea/thiourea using neutral alumina gave 4,4a,5,6,7,8-hexahydro-377-pyrido[4,3- pytimidine derivatives 610 and 611, respectively (Equation 52) <2005IJB2527>. 

The reactions of 2-piperidineacetamides with aqueous formaldehyde [68BRP1114397 72JCS(P2)1920] or with A, A-dimethylcarboxamide dialkyl acetals (84EUP104647 85JMC1285) gave perhydro- or 4,4a,5,6,7,8-hexahydro-3/7-pyrido[l,2-c]pyrimidin-3-ones, respectively. Reaction of 1-chlorocarbonyl-2-[l-cyano-l-phenyl-3- [A,A-di(2-propyl)amino]propyl piperidine with ammonium hydroxide or primary amines at 80°C afforded... 

Acyl-2,3-dihydro-lH-pyrido[l, 2-c]pyrimidin-4-ones were obtained when 2-vinylpyridine was reacted with acyl isocyanates (75IZV2608), Cyclocondensation of 3-methoxy-2-(2-oxopropyl)piperidine and phenyl isothiocyanate in boiling ethylene dichloride afforded 3-methyl-5-meth-oxy-2-phenyl-2,4a,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione (55JOC136). 

From the incubated reaction mixture of benzylamine and butyraldehyde or 2-ethyl-2-hexenal in the presence of dissolved oxygene in a mixture of 90% methanol 0.1 A/ phosphate buffer at 37°C for 48 h, 2-benzyl-l-phenyl-6-propyl-4,5,7-triethyl-2,3,5,6,7,8- and -2,4a,5,6,7,8-hexahydro-l//-pyrido[l,2-cjpyrimidines could be isolated (89MI2). 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

An X-ray crystal structural determination revealed that the 8-carboxyl group of cij-4fl,8-H-l,3,4,4a,7,8-hexahydropyrido[l,2-c][l,3]oxazine-8-carboxylic acid is in a pseudoaxial position (81JA7573). The crystal structure of 4-phenyl-2- 4-[4-(2-pyrimidinyl)piperazin-l-yl]butyl -2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c][l,3]oxazine-l,3-dione was determined by an X-ray investigation (95ZK899). 

Treatment of 2-substituted 3-amino-4-cyano-2,4a,5,6,7,8-hexahydro-l/f-pyrido[l,2-c]pyrimidin-l-ones (130) with acyl chlorides afforded tricyclic 3,5-disubstituted 2,5,6,8,9,10,ll,lla-octahydro-l//-pyrido[l,2-c]pyrimido[5,4-e]pyrimidine-l,6-diones (131) (90MI3 93MI1, 93MI3). 

Ab initio Hartree-Fock and density functional theory (DFT) calculations were performed to study the transition state geometry in intramolecular Diels-Alder cycloaddition of azoalkenes 18 to give 2-substituted 3,4,4a,5,6,7-hexahydro-87/-pyrido[l,2-A]pyridazin-8-ones 19 (Equation 1) <2001JMT(535)165>. 

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