3- Hydroxy-3- perhydropyrido oxazine

Hydroxy group of perhydropyrido[l,2-A][l,2]oxazin-8-one 23 (R = H) was protected with t-BuPh SiCl in the presence of imidazole in DMF (OOOL2955, 01JOC3338). 

Substituted perhydropyrido[l,2-c][l,3]oxazines 83 were obtained by the cyclization of l-(/er/-butoxycarbonyl)-2-(2-hydroxyalkyl)piperidines 104 in pyridine on the action of MeS02Cl at room temperature (96CJC2434). Cyclization of c/5-2,6-H- l-(methoxycarbonyl)-2-(2-acetoxyhexyl)-9-methox-ypiperidines 105 and 106 in THF in the presence of KO/-Bu yielded 3-butyl-9-methoxyperhydropyrido[l,2-6 ][l,3]oxazin-l-ones 94. Treatment of l-(/erc-butoxycarbonyl)-2-[2-hydroxy-2,2-di(2-propyl)ethyl]piperidine with NaH in boiling THF yielded 3,3-di(2-propyl)perhydropyrido[l,2-c][l,3] oxazin-l-one (01JA315). 

Treatment of an epimeric mixture of l-hydroxy-8-methylene-4-phenyl-perhydropyrido[2,l-c][l,4]oxazines with 4% aqueous solution of OSO4 in aqueous THE in the presence of NaI04 at room temperature gave an epimeric mixture of l-hydroxyl-8-oxo derivatives (OOJOC4435, 01EJOC2385). 

Alkoxy-3-(4-biphenyl)perhydropyrido[], 2-c][], 4]oxazines were obtained from 3-hydroxy derivative with PrOH and Br(CH2)30H in a boiling acidified medium (00JMC609, 00MIP13). Spontaneous dehydration of b-hydroxy-1,3,4,6,7,1 lZ -hexahydro[l,4]oxazino[3,4-n]isoquinolin-4-one 258 in CHCI3 gave 3,4,6,7-tetrahydro derivative 259 (97JOC2080). 

Hydroxy-3-(4-biphenyl)perhydropyrido[l,2-c][l,4]oxazine was obtained in the reaction of 2-piperidinemethanol and 4-bromoacetylbiphenyl in a mixture of acetone and Et20 at room temperature (00JMC609, 00MIP13). Perhydropyrido[l,2-c][l,4]oxazin-l-one 298 was obtained in the reaction of quinoline derivative 297 and chloroacetyl chloride (OOMIPl). 

Reduction of hydroxy lactams (154) with a complex of DIBAL and butyl-lithium gave an inseparable mixture of perhydropyrido[2,l-b][l,3]oxazines (155) (92TL507). When Red-Al was used as a reducing agent, side products... 

Cyclization of the piperidone derivative (158) gave rise to diastereomer-ically pure perhydropyrido[2,l-h][l,3]oxazin-6-one (159) (94JA10819). Heating l-(3-methoxy-l-propyl)-2-hydroxy-3-cyano-4-methylpyridin-6(l//)-one in 25% sulfuric acid at 80°C for 2 h gave 8-methyl-6-oxo-2,3,4,6-tetrahydropyrido[2,1 -fo][ 1,3]oxazine-9-carboxamide (89EUP316779). 8-(4-Methoxyphenyl)-2,3,4,6-tetrahydropyrido[2, -b [1,3]oxazine-2,6-dione was obtained by cyclization of 3-[4-(4-methoxyphenyl)-2,6-dioxo-l,2,3,6-... 

Reaction of 4-aryl-7-iodoperhydropyrido]2,l-c][l,4]oxazin-6-ones (07USA2007/0117839, 08WOP2008/013213) and 7-iodo-6-oxo-4-(3,4,5-tri-fluorophenyl)perhydropyrido[2,l-a]pyrazine-2-carboxylate (07USA2007/ 0117839) with P(OEt)3 at 120 °C for 2 h afforded 7-phosphonic acid diethyl esters. 3-Hydroxy-6-arylperhydropyrido[2,l-c][l,4]oxazin-4-ones first were reacted with triphenylphosphonium bromide in refluxing MeCN, then with 3-methoxy-4-(4-methyl-lH-imidazol-l-yl)benzaldehyde at ambient temperature in the presence of NEt3 to provide (Z)-3- l-[3-methoxy-4-(4-methyl-lH-imidazol-l-yl)phenyl]methylidene] derivatives (07USA2007/ 0117798, 08USA2008 /0207900). 

The reaction of 1,3-disubstituted perhydropyrido[l,2-c][l,3]oxazines (69) and 7-(benzothiazol-l-yl)-6,7-dihydro-17/,3//,5//-pyrido[3,2,l-iy][3,l]benz-oxazine with Grignard reagents led to 2-(/V-substituted 2-piperidyl)ethanols (70) (50JA358 58CLY2081) and l-benzyl-4-(benzotriazol-l-yl)-8-hydroxy-methyl-l,2,3,4-tetrahydroquinoline (95JOC3993), respectively. 

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