2- hexahydropyrido

Ester and pivaloyloxy groups, present in a side chain of 1,2,3,5,6,7-hexahydropyrido [3,2,1-zy]quinazolin-l-ones, were hydrolyzed to carboxyl and hydroxyl groups, respectively under basic conditions (07JP2007131577). 

The Mannich reaction of 2-oxo- (146) and 2-thioxotetrahydro-pyrimidines yields the hexahydropyrido[4,3-d]pyrimidin-2(l//)-one (147) and the corresponding thione. 

Neither deuterium incorporation nor double bond migration occurred when 6-cyano-2,3,4,8,9,9n-hexahydropyrido[2,l-Z)][l,3]oxazine (44) was... 

Depending upon the structure of the substrates 49, 52, and 56 hexahydropyrido[l,2-n]-[3,l]benzoxazines 50, 54, 2-aminobenzaldehyde 53, 1-substituted piperidones 51, 55, 57, 3,4,5,6-tetrahydropyridinium salt 58, or their mixture was obtained during the oxidation of 1-(2-hydroxymethyl-, 2-formyl- and 2-acetylphenyl)piperazines (49, 52, 56) with Hg(II)-EDTA complex (Schemes 6-8) (79AP219, 98ZN(B)37, 98ZN(B)1369). 

Irradiation of piperidine 62 in CH2CI2 at concentration of 3mg/ml in the presence of 1-methylimidazole using a high-pressure mercury lamp (150 w) yielded 2-phenyl-4,6,7,8,9,9n-hexahydropyrido[2,l-h][l, 3]oxazin-4-one (01 SI258). 

Reaction of 5n,6,7,8,9,l l-hexahydropyrido[2,l-f ][l,3]benzothiazine-7,l 1-dione (47, X = S, R = H) and 2-amino-6-fluorobenzamidine dihydrochloride in boiling EtOH yielded a diastereomeric mixture of spiro derivatives 48 (X = S, R = H), which were separated by flash column chromatography (OOMIPl). 

Stereostructure of ethyl c/>4u,7-H-7-phenyl-8-cyano-2-oxo-2,3,4,4u,7,8-hexahydropyrido[l,2-6][l,2]oxazine-8-carboxylate was confirmed by X-ray analyses. It justified a trans ring junction of the bicycle (00OL4007). 

Hydrogenation of 2,4u,5,6,7,8-hexahydropyrido[l,2-A][l,2]oxazin-8-onei 14 over 10% Pd/C catalyst gave perhydro derivatives 15 (96JCS(P1)1113, OOOL2955, 01JOC3338). 

Perhydropyrido[l,2-A][l,2]oxazines are applied as key intermediates in a stereospecific total syntheses of (-)-pumiliotoxin C and 5-e/ /-pumiliotoxin C(96JCS(P1)1113), and the marine alkaloid)—)-lepadins A, B, C (OOOL2955). (2-Pyridyl)propionic acids 13 can be regioselectively prepared via 2,3,4, 4fl,7,8-hexahydropyrido[l,2-A][l,2]oxazin-2-ones 12 (00OL4007). 

Treatment of l-arylsulfonyl-2-(l-iodoalkyl)piperidines 48 (R = H) with 2.7 equiv. of BusSnH in the presence of azobisisobutyronitrile (ABIN) furnished a mixture of 7,8,9,10,10u,ll-hexahydropyrido[l,2-ft][l,2]ben-zothiazine 5,5-dioxides 50, 2-benzylpiperidines 51 and l-arylsulfonyl-2-alkylpiperidines 52 in a radical process (Scheme 6) (77TL631,78JCS(CC)166, 80JCS(CC)142). The yield of 7,8,9,10,10u,ll-hexahydropyrido[l,2-6][l,2]... 

Reaction of tetrahydropyridin-4-one 119 and l,r-carbonyldiimidazole furnished l,3,4,4n,5,6-hexahydropyrido[l,2-c][l,3]oxazine-l,6-dione 120 (99JA2651). Similarly, pyrido[l,2-c][l,3]oxazine-l-one 121 and [1,3] oxazino[4,3-n]isoquinoline-4-one 122 were prepared from the respective 2-(2-hydroxypropyl)piperidine and l-(2-hydroxypropyl)-1,2,3,4-tetrahy-droisoquinoline (99JOC3790). Reaction of a 2 1 diastereomeric mixture of l-(l,2-dihydroxyethyl)-6,7-dihydroxy-l,2,3,4-dihydroisoquinolines 123 and 124 with l,l -carbonyldiimidazole gave a 2.7 1 mixture of 1,9,10-trihy-droxy-l,6,7,ll/)-tetrahydro-2//,4//-[l,3]oxazino[4,3-n]isoquinoline-4-ones 125 and 126, which were separated on preparative TLC plate (99BMC2525). 

The N(2) atom of l-iminoperhydropyrido[l,2-c]pyrimidine 153 was selectively deprotected by treatment with NaH to yield 1-amino-4,4n,5,6,7,8-hexahydropyrido[l,2-c]pyrimidine 154 (00TL1849). 

Michael addition of dialkyl cuprate reagents to optically active 4-phenyl-l,3,4,6,7,8-hexahydropyrido[2,l-c][l,4]oxazin-l-one afforded stereoselec-tively 9-alkylperhydro derivatives 228 in a mixture Et20 and THF at -40 °C in the presence of Cul in good yields (99TL3699). 

Amino-6,6n,7,8,910-hexahydropyrido[2,l-c][l,4]benzoxazine was reacted with ethyl 4,4,4-trifluoroacetoacetate in boiling benzene for 12-16 h, then the reaction mixture was concentrated in vacuo and the residue was treated with cone. H2SO4 at 100°C to give tetracyclic 11-trifluoromethyl-l,2,3,4,4a,5,8,9-octahydropyrido[l, 2 4,5][l,4]oxazino[3,2-a]quinolin-9-one in 30% yield (OlMIPl). 

The lipophilicity (7 m value) and specific hydrophobic surface area of pyrido[l,2-a]pyrazinium-l-olates 342 and -3-olate 343, and l-(4-chlorophe-nyl)-l-hydroxy-l,2-dihydropyrazino[2,l-a]isoquinolinium salt (344) has been measured by reversed-phase thin-layer chromatography (98MI13). Partition coefficient (log/ ) of 9-bromo-5-[(A-phenylaminocarbonyl)-methyl]-l,2,3,5,6,7-hexahydropyrido[l,2,3- fc]quinoxaline-2,3-dione was calculated to be 2.78 (97JMC4053). 

---