2.3.4.6- Tetrahydro oxazino 3,2/> isoquinolin-6-ones

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). 

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). 

Two reports deal with the E I mass spectra of some related, stereoisomeric and partly saturated 1,3- and 3,l-benzoxazino-l,3-benzoxazines (95RCM1035) and of some substituted stereoisomeric l,6,7,llb-tetrahydro-2//,4//[l,3]oxazino[4,3-fl]isoquinolines and l,6,7,llb-tetrahydro-2//[l,3]ox-azino[4,3-a]isoquinolin-4-ones (95RCM998, 95RCM1035). 

Heating a mixture of 2-(carboxymethyl)benzoic acids and 3-amino-propanol in o-dichlorobenzene in the presence of p-toluenesulfonic acid yielded 2,3,4,6-tetrahydro[l,3]oxazino[3,2-b]isoquinolin-6-ones (78BEP 866987, 78GEP2756067 79CPB2372). Similar reaction between o-benzoylphenylacetic acid and 3-aminopropanol in toluene resulted in 11 b-phenyl-2,3,4,6,7,116-hexahydro[l,3]oxazino[2,3-a]isoquinolin-6-one (71MI1). Reaction of 2-(2-bromoethyl)benzaldehyde and 3-aminopropanol in ethanol led to 2,3,4,6,7,llb-hexahydro[l,3]oxazino[2,3-a]isoquinoline (61AP645). 

JA11707), 4-cyano-3-phenyl-3-trifluoromethyl-2,3-dihydro-lH-pyrido [l,2-c]pyrimidin-l-one (05MI1), and 10-(ferf-butyl)-3-methylene-3,4,4fl,5-tetrahydro-3H-[l,3]oxazino[3,4-b]isoquinolin-l-one (07EJ02015) under either acidic or basic conditions. 

Cyclocondensation of the cyclic anhydride 212 and ethyl o-fluoroben-zoylacetate with the imino ether 213 gave l,3,4,6-tetrahydro[l,4]ox-azino[4,3-h]isoquinolin-6-one (214) (81JHC767) and [l,4]oxazino[4,3-a]quinoline-5-carboxylate (215) (80JHC1729), respectively. 

Heating ethyl 6-methylpicolinate and ethylene oxide in methanol in a pressure bottle afforded 6-methylperhydropyrido[2,l-c][l,4]oxazin-l-one (66JMC311 68USP3388128). Similarly, l,3,4,6-tetrahydro[l,4]oxazino[4,3- >]isoquinolin-l-ones were prepared in the reactions of ethyl 1,2,3,4-tetrahy-droisoquinoline-3-carboxylates and ethylene oxide (85MI2). 

Phenylimino)-l-hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,ll -hexahy-dro[l,3]oxazino[4,3-a]isoquinoline was prepared from 4-methylimino and 4-thione derivatives in the presence of HgO and 4-methylthio-l,6,7,llh-tetrahydro-2//-[l,3]oxazino[4,3- ]isoquinolinium salt with aniline (85GEP3510526). 4-Methylthio-l-hydroxymethyl-9,10-dimethoxy-l,6,7,116-tetrahydro-2//-[l,3]oxazino[4,3-a]isoquinolinium iodide was obtained from the l,2,4,6,7,116-hexahydro-4-thione derivative with methyl iodide (85GEP3510526). 1-Hydroxymethyl-9,10-dime thoxy-1,2,4,6,7,116-hexahy-dro-[l,3]oxazino[4,3-fl]isoquinolin-4-thione was obtained from its 4-one derivative by treatment with P4S10 in pyridine (85GEP3510526). 

Treatment of 8-hydroxymethyl-l,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroquinoline-8-carboxylic acid, or l-(2-hydroxyethyl)-l,2,3,4-tetrahydroisoquinolines with COCI2 in the presence of a base furnished l,5,6,7-tetrahydro-3//-pyrido[3,2,l-(/ ][3,l]benzoxazin-3-one (92JMC1076), the -1,3-dione (102) (78JHC645), and l,2,4,6,7,llft-hexahydro[l,3]oxazino[4, 3-a]isoquinolin-4-ones (92T4937), respectively. 

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