2,3,4,5 Tetrahydro 1 methyl 7 1/7-azepine

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

Extension of this work by reacting 5-nitropyrimidine with 0,0-ketene acetals and with other cyclic and non-cyclic enamines showed that also with these electron-rich dienophiles the addition is regioselective and gives rise to the formation of 2-mono- or 2,3-disubstituted 5-nitropyridines (Scheme 30). Thus, reaction of 5-nitropyrimidine with the cyclic N,S-ketene acetals 4,5-dihydro-1 -methyl-2-methylthiopyrrole and 4,5,6,7-tetrahydro-1 -methyl-2-methylthioazepine gives in low yields 2,3-dihydro-1-methyl-5-nitropyr-olo[2,3-h]pyridine and the 5,6,7,8-tetrahydro-9-methyl-3-nitropyrido [2,3-Z)]azepine, respectively (89T2693) (Scheme 30). 

Reports of 1,3-dipolar cycloadditions with l -azepines are uncommon. Methyl l//-azepine-l-carboxylate, however, with iV-phenylbenzylideneamine iV-oxide (42) undergoes cycloaddition at the C4 —C5 double bond to yield a 1 1 mixture (48 %) of the two stereoisomers of methyl 2,3-diphenyl-2,3,3a,8a-tetrahydro-6//-isoxazolo[4,5-r/]azepine-6-carboxylate (43).83 268... 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

Alkylation of 3-methyl-1,2,4,5-tetrahydro-3//-3-benzazepin-2-one in THF-DMF solution containing sodium hydride, with primary and secondary alkyl halides and with a-bromoesters, results predominantly in 1-monoalkyl derivatives, whereas with w,w-dibromoalkanes, 1,1-spiro derivatives are formed (80T1017). Apparently, 6,7-dihydro-5//-dibenz[6,rf]azepin-6-one does not condense with benzaldehyde or with nitrosobenzene at the active methylene group (55JA3393). 

A-f2- 5-f(/ /.S )-l-Carbamoyl-2-phenylethyl]-2,3,6,7-tetrahydro-2-oxo-l/f-azepin-l-yl)-3-methylbutan-oyl]valine Methyl Ester (39) ... 

V- 2-f2,3,6,7-Tetrahydro-2-oxo-5- (i /S)-2-phenyl-l-f(serinylalaninylalaninyl)amino]ethyl)-l//-azepin-l-yl]-3-methylbutanoyl valine Methyl Ester (44) ... 

Methyl-2-oxo- XI/2, 569 5-Methyl-2-oxo- VIII, 670 3H-Azepin 2-Methoxy-4,5,6,7-tetrahydro- XI/2, 578 Azet 3,3(bzw. 3,4)-Dimethyl-2-ethoxy-3,4-dihydro- E16c, 929 (En —OR-Bildung)... 

Azepin 2-ChIor-3-chlorcarbonyl-l-methyl-4,5,6,7-tetrahydro- E15/2 1646 (R —CH2 — CO —NR2 + COCl2)... 

Azepin 1 -Acetyl-2-methoxy-4,5,6,7-tetrahydro- El 5/2, 1778 (a-OR-imin +R-CO-C1) Bernsteinsaure 3-Methyl- -1-butylester-4-nitril VIII, 270 Bicyclo 3.1.1 beptan 6-Hydroximi-nomethyl-(2/ ,6S)-2-hydroxy-6-methyl- IV/5a, 721 Bicyclo 4.1.0 heptan 7-entfo-Amino-7-methoxycarbonyl- E21c, 3266 (cycl. En + cycl. N-CH2-C(OR) = N) 1,3-Butadien 1-Diethylaminocarbo-nyloxy- EI5/1, 14 (En-al + Cl-CO-NR2)... 

Azepin 4,5-Bis-[trimethylsilyloxy]-l-methyl-2,3,6,7-tetrahydro-E15/2, 1297 (ROOC-A-COOR + Na(RjSi-Cl)... 

According to a recent report, however, the carbonyl ylides formed under these conditions may isomerize and lead to adducts different from those normally expected87. Thus, (5)-l-acetyl-2-(diazoacetyl)pyrrolidine (8). derived from /V-acetyl-i.-proline, upon treatment with dimethyl butynedioate in the presence of a catalytic amount of rhodium(II) acetate dimer at 25 °C affords only 10% of the expected adduct dimethyl 5,8-epoxy-2,3,5,8,9,9a-hexahydro-5-methyl-9-oxo-lH-pyrrolo[l, 2-o]azepine-6,7-dicarboxylate (9). Instead, dimethyl 1,2,8,9-tetrahydro-5-methyl-l-oxo-3a//,7//-furo[3,2-g]pyrrolizine-3a,4-dicarboxylate (10) is obtained in 87% yield. The formation of this product is explained via an isomeric ylide87 and thus occurs with complete loss of chiral information. 

Condensation of 57 with homoveratraldehyde (60) in the presence of molecular sieves, followed by sodium borohydride reduction, affords the chromium tricarbonyl complex 61 in moderate overall yield. The acid-promoted cyclization of 61 proceeds with retention of configuration to afford, after air decomplexation, optically pure (/ )-( + )- -phenyl- 3-methyl-l,2,4,5-tetrahydrobenz[d]azepine (62) (Scheme 12) [14]. The l,2,4,5-tetrahydro-3//-benz-[benzazepine alkaloids . Moreover, the dopaminergic activity possessed by this class of compounds resides mostly in the (i )-enantiomer [15,16]. 

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