2- hexahydropyrido compounds

Depending on the reaction temperature and reaction time, tetrahydroisoquinoline 357 afforded different mixtures of 1,2,3,4,11,11 a-hcxahydro-6//-pyrazino[ 1,2-3]isoquinolines 358-361 and tetracyclic compound 362 (Scheme 30) <2005JA16796>. Each of the individual diastereoisomers 358-361 could be transformed into the compound 362. z7r-3//,4a//-3-Phcnylpcrhydropyra/ino[ 1,2-7]isoquinoline-l,4-dione was prepared via automated parallel solid-phase synthesis on Kaiser oxime resin <1998BML2369>. l,2,3,5,6,7-Hexahydropyrido[l,2,3-r/f ]quinoxaline-2,5-dionc was obtained by catalytic hydrogenation of ethyl 3-(2-oxo-l,2,3,4-tetrahydro-5-quinoxalinyl)acrylate in the presence of TsOH over 5% Pd/C catalyst under 40 psi of hydrogen <1996JME4654>. 

Compound 107 was also treated with an equimolecular ratio of CS2 and double molarity of methyl iodide to yield the corresponding A-methyl derivative 109 (50%) the latter, in turn, underwent cyclization when treated with aniline in 1 1 or 1 2 molar ratio, affording 3,8-diphenyl-5,6,7,8,9,10-hexahydropyrido-9-imino-7-methylthio-6-oxo[3,4-/][l,2,4] tria-zolo[3,4-A][l,3,4]thiadiazepine 110 in 39% yield (Scheme 11). 

Tetracyclic compound 197 was obtained when 4,4,4-trifluoroacetate and 3-amino-6,6a,7,8,9,10-hexahydropyrido[2,l-c][l,4]benzoxazine 195 was heated in benzene, then the condensation product 196 was cyclized by heating in PPA (07JMC2486). 

In a sodium ethoxide catalyzed condensation of 3,5-bis(arylmethylene)-4-piperidones 22 with ureas or thioureas, one of the exo-methylene functions is used to build up the pyrimidine part of a 8-methylene-l,4,5,6,7,8-hexahydropyrido[4,3-ethanolic solution of 1-methyl-3,5-bis(ferrocenylmethylene)-4-piperidone with an excess of thiourea in the presence of sodium ethoxide, the corresponding pyrido[4,3-r/]pyrimidine-2-thiol is obtained.512 The use of guanidine in this reaction affords the corresponding 2-amino compounds.513... 

Theoretical calculations on these classes of compounds have not yet been recorded. The structures of two hexahydropyrido[2,l-6][l,3,4]oxadiazines (180) and (181) have been determined by x-ray crystallography. The analysis revealed that the six-membered rings are chair shaped and the ring fusion is cis <93AX(C)1786>. 

Differential thermal analysis was conducted for 2-methoxy-7,8,9,10-tetrahydropyrido[2,l-c][l,2,4]benzothiadiazine-5,5-dioxide, and it was found that this compound exists in two polymorphic forms, one of them being remarkably unstable. Detailed conformational analyses for hexahydro[2,l-6][l,3,4]oxadiazines <93AX(C)1786> and hexahydropyrido[2,l-e][l,2,5]oxadiazines <92AP(325)157> were described on the basis of x-ray and NMR studies, respectively. 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

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