1 - - 2 - methyl 6,7 -dimethoxy -1,2,3,4 - tetrahydroisoquinoline

Carbet hoxy methyl-6,7-dimethoxy-1, 3,4-tetrahydroisoquinoline Tetrabenazine... 

Procedure 3 Dynamic Kinetic Resolution of 6,7-Dimethoxy-l-methyl-1,2,3,4-tetrahydroisoquinoline... 

To a two-neck 50 mL round-bottom flask was added 6,7-dimethoxy-l-methyl-l,2,3,4-tetrahydroisoquinoline (3.093 g, 14.92 mmol), C. rugosa lipase (1.5 g, 1410 units/mg), pentamethylcyclopentadienyliridium(III) iodide (34.3 mg, 0.030 mmol) and toluene saturated with water (25 mL), resulting in an orange solution containing some insoluble amine. 

Anodic oxidation of 4-(3,4-dimethoxybenzyl)-6,7-dimethoxy-2-methyl-l,2, 3,4-tetrahydroisoquinoline (168) in trifluoroacetic acid-dichloromethane-Bu4NBF4, using controlled-potential electrolysis (-I-1.2V versus SCE) affords the corresponding 3,4-dihydroisoquinolinium salt (169), and the 4-(3,4-dimethoxybenzylidene)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquino-linium salt (170) was formed at higher anodic potential (+1.9V versus SCE) at a carbon-felt anode256 [Eq. (104)]. 

Treatment of l-(3, 4 -methylenedioxybenzyl)-2-methyl-6,7-dimethoxyisoquinolinium iodide with lithium aluminium hydride in ether followed by immediate treatment with 2N hydrochloric acid resulted in formation of an intense red-violet colour which very quickly faded to yellow. Basification of the reaction mixture and extraction with chloroform gave an oil which was reduced by treatment with sodium borohydride in ethanol. This gave a product which was isomeric with, but different from, l-(3 ,4 -methylenedioxybenzyl)-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, the expected product from this sequence of reactions. 

The anodic oxidation of 4-(3,4-dimethoxybenzyl)6,7-dimethoxy-2-methyl-l,2,3,4-tetrahydroisoquinoline does not afford the intramolecularly aryl-aryl coupled prod-... 

Similar methodology was used in the synthesis of 3-methyl derivatives of the alkaloids thalactamine, doryanine, and 6,7-dimethoxy-A-methyl-l(2//)-isoquinolone652. The S l reaction between 0rr/20-halogenobenzylamines and enolates derived from a series of ketones and aldehydes affords 1,2-dihydroisoquinolines, from which the isoquinoline derivatives can be obtained by dehydrogenation and the 1,2,3,4-tetrahydroisoquinolines by reduction653. The products of the S l reactions of (2-halo-4,5-dimethoxyphenyl)acetic... 

The biosynthetic work on mescaline in the peyote cactus L. williamsii and in the Peruvian cactus T. pachanoi has led to the formulation of biosynthetic pathways according to Scheme 2. A major pathway probably involves decarboxylation of tyrosine followed by hydroxylation to yield dopamine. Dopamine is methylated on the meta hydroxy group to 4-hydroxy-3-methoxyphenethylamine (3-methoxytyramine) which then undergoes hydroxylation to the key intermediate 4,5-dihydroxy-3-methoxyphenethylamine (20). Para-O-methylation of 20 yields 3,4-dimethoxy-5-hydroxyphenethylamine (21), which is the immediate precursor of the main phenolic tetrahydroisoquinolines of peyote. Alternatively, meta-O-methylation yields 3,5-dimethoxy-4-hydroxyphenethylamine (19), which is further efficiently methylated to mescaline. Parallel pathways involving N-methylated compounds probably exist in these cacti (10). 

Dimethoxy-l,2,3,4-tetrahydroisoquinoline hydrochloride Isoquinoline, l,2,3,4-tetrahydro-6,7-dimethoxy-, hydrochloride (8,9) (2328-12-3) (S)-N,N-Dimethy1-N -(l-tert-butoxy-3-methyl-2-butyl)formamidine Methanimidamide, N -[ -[(1,l-d1methy 1 ethoxy)methyl]-2-methylpropyl]-N,N-dimethyl-. (S)- (11) (90482-06-7)... 

The alkaloid was synthesized by the Ullmann condensation of l-(3 -bromo - 4 - benzyloxybenzyl) - 2 - methyl - 6,7 - dimethoxy -1,2,3,4 - tetra-hydroisoquinoline (XXXIV) and l-(4 -benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (IX) followed by removal of the benzyl groups (40). 

Reduction of 9,10-dimethoxy-l-(un)substituted 3-substituted 1,3,4,6,7, llh-hexahydro-2//-pyrimido[6,l-a]isoquinolones with NaBH4 in acetic acid afforded ring-opened 6,7-dimethoxy-2-methyl-l-[2-(substituted amino)-2-oxo]ethyl-l,2,3,4-tetrahydroisoquinolines (92GEP4104257). 

Perhydropyrido[l,2-c][l,3]oxazin-l-ones were prepared in the reaction of the appropriate 2-(2-piperidyl)ethanols and ethyl chloroformate (63AP38) in the presence of sodium ethylate in boiling benzene, or when 2-(2-piperidyl)ethanol was reacted with dimethyl carbonate in the presence of sodium methylate (91X1311). l-Hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,llb-hexahydro-[l,3]oxazino[4,3-fl]isoquinoline-4-oneand 4-thione were prepared from l-[bis(hydroxymethyl)methyl]-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with ethyl chloroformate in the presence of sodium methylate, and thiophosgene in the presence of NEts, respectively... 

The catalytic and chemical reduction of the 3-methyl-3,4-dihydrobenzyliso-quinoline (56) has been studied (Scheme 2)3 Catalytic hydrogenation of (56) in acidic ethanol gave the ds-l,2,3,4-tetrahydroisoquinoline, c/5-(57), as the sole product whereas reduction with NaBH4 produced a 25 1 mixture in favour of trans- Sl). The same report also describes the Bischler-Napieralski cyciization of N-2-[l-(2,5-dimethoxy-4-methylphenyl)propyl]-3,4-dimethoxyphenylaceta-mide to give, in addition to the normal product (56), a number of neutral compounds which shed some light on the mechanism of this reaction." One of... 

Boc protection of the amine, complexation with hexacarbonylchromium, and then amine deprotection with neat formic acid provides (R)-( + )-halostachine(tricarbonyl)chromium(0) (57). Treatment of 57 with 3,4-dimethoxybenzyl bromide in dichloromethane affords in 36% yield (i )-( + )-tricarbonyl f -2-[3,4-dimethoxybenzyl(methyl)amino]-l-phenylethanol -chromium(O) (58), which undergoes a highly selective acid-promoted cyclization that proceeds with retention of configuration to yield, after decomplexation, optically pure (R)-(-h)-6,7-dimethoxy-2-methyl-4-phenyl-l,2,3,4-tetrahydroisoquinoline (59) in moderate yield (Scheme 11) [13]. 

Pseudocodamine (LIV) was found to be l-(3-methoxy-4-hydroxybenzyl)-2 - methyl -6,7- dimethoxy -1,2,3,4-tetrahydroisoquinoline. Ethylation with diazoethane led to an ethyl ether (m.p. 176-180°) which could be oxidized to A -methylcorydaldine and 3-methoxy-4-ethoxybenzoic acid (LXXIV). 

---