8-Methoxy-1,2,3,4-tetrahydro-isoquinolines

The thermal condensetion of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxy-phenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy4-hydroxy-phenethyl-p-benzyloxyphenylacetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the 1-(p-benzyloxybenzyl)-6-meth-oxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline, which is methylated with formaldehyde and formic acid giving 1 (p-benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydro-isoquinoline with a yieid of 90%. 

Among the amines that have been resolved with (-)-DAG are a-phenylethylamine (a-methylbenzenemethanamine), [R-(R, R )]-2-amino-l-(4-nitrophenyl)-l,3-propanediol, 1,2,3,4,5,6,7,8-octahydro-l-(4-methoxyphenylmethyl)isoquinoline, 3-methoxymorphinan, 1,2,3,4-tetrahydro-7-methoxy-4-phenylisoquinoline, 3-hydroxy-i 7-methyl-morphinan, l,2,3,4-tetrahydro-6,7-dimethoxy-l-[3,4-(methylenedi-oxy)phenyl]isoquinoline, l,2,3,4-tetrahydro-6,7-dimethoxy-l-(3,4,5-tri-methoxyphenyl)isoquinoline, 2-[4-(phenylmethoxy)phenyl]-2-(3,4-di-methoxyphenyl)ethanamine, A-norlaudanosine (tetrahydropapaver-ine), and l,2,3,4-tetrahydro-6,7-dimethoxy-l-[3-methoxy-4- phenyl-methoxy)phenyl]isoquinoline. 

Brochmann-Hanssen E, Cheng CY (1984) Biosynthesis of a narcotic antagonist. Conversion of N-allylnorreticuline to N-allylnormorphine in Papaver somniferum. J Nat Prod 47 175-176 Brochmann-Hanssen E, Furuya T (1964) A new opium alkaloid. Isolation and characterization of ( )-l-(3 -hydroxy-4 -methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydro-isoquinoline [( )-reticuline]. Planta Med 12 328-333 Brochmann-Hanssen E, Nielsen B (1965) (+)-Reticuhne - a new opium alkaloid. Tetrahedron Lett 1271-1274... 

K1.6 Cryptosty lines 1 -(4, 5 -dimethoxy-2 -hydroxybenzyl)-7-methoxy-2-methyl-l, 2,3,4-tetrahydro isoquinoline Kl.l... 

Among the amines that have been resolved with (-)-DAG are a-phenylethylamine (a-methylbenzenemethanamine),s [R-(R, R )]-2-amino-l-(4-nitrophenyl)-l, 3-propanediol,61,2,3,4,5,6,7,8-octahydro-l-(4-methoxyphenylmethyl)isoquinoline, 3-methoxymorphinan, 1,2,3,4-tetrahydro-7-methoxy-4-phenylisoquinoline, 3-hydroxy-A7-methyl-... 

CN 7-amino-4,5,6-triethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-l,3-dioxoIo[4,5-g]isoquinolin-5-yl)-1 (3//)-isobenzofuranone... 

R,5 S)-2-[(2-bromomethylphenyl)methyl -2,5-dihydro-5-mpropyi-3,6-dimethoxy-2-meth ipyrazme >97% de 6 (3, 11 aR)-3,4,6, t t-tetrahydro-3-isoprop I-l-methoxy-U a-methyl-4-oxopyrctzino[l, 2-b isoquinoline yield 75% 97% de... 

The structures of anhydro 9,9-dimethyl-4-hydroxy-2-oxo-6,7,8,9-tetrahy-dro-2H-pyrido[2,l- >] [1,3]thiazinium hydroxide (95JOC3795,95T6651) and llh-isopropyl-2-methoxy-3,4-diphenyl-2,6,7,llh-tetrahydro-[l,3]thiazino-[2,3-a]isoquinoline [79AX(B)1285] were determined by means of X-ray diffraction analysis. 

Treatment of 6-hydroxymethyl-2-methyl-7-methoxy-l,2,3,4-tetrahydro-6//-pyrazino[l,2-b]isoquinolin-4-one (138) with NBS, then with methyl acrylate in the presence of NEt3 afforded a 1 5 diastereomeric mixture of tetracyclic derivatives 139 and 140 (95JOC6791). Reductive radical decya-nation of 3-methyl-5,5-dicyano-2,3,4.4a,5,6-hexahydro-l//-pyrazino [1,2-a]-quinoline with a mixture of Bu3SnH and 2,2 -azobisisobutyronitrile afforded nearly a 1 1 mixture of diastereomers of the 5-cyano derivative (95TL5159). 

Isomerization of benzo[/]-l,5-diazabicyclo[3,2,2]nonene in 8.8 N HBr at 140°C yielded l,2,3,5,6,7-hexahydropyrido[l,2,3-de]quinoxaline (83 KGS677). Photolysis of dimethyl l-(quinolin-8-yl)-l,2,3-triazole-4,5-di-carboxylates in MeCN resulted in stable an/tydro-2,3-dimethoxycarbonyl-3//-pyrido[l,2,3-de]quinoxalin-4-ium hydroxides [87JCS(P1)403]. 6-Hy-droxymethyl-2-methyl-7-methoxy-l,2,3,4-tetrahydro-6//-pyrazino-[1,2-h]isoquinolin-4-one (138) was prepared from 5- [A-methyl-Ar-(ethoxy-... 

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