6.7- Dimethoxy-4 isoquinoline

Permanganate oxidation of papaverine in neutral medium furnishes m-hemipinic acid (V), veratric acid (VI), papaverinic acid (a-veratroylcincho-meronic acid) (VII), and pyridine-2,3,4-tricarboxylic acid (VIII). The last-named product (VIII) may serve as evidence for the point of attachment of the nitrogen-free portion of the isoquinoline system. Dimethoxy-isoquinolines are oxidized to pyridine-3,4-dicarboxylic (cinchomeronic) acid, but papaverine yields VIII under analogous conditions, thus marking position 1 as the connecting point. 

Anodic oxidation of l-(3, 4 -dimethoxybenzyl)-6,7-dimethoxy-isoquinolines at platinum anodes in acetonitrile affords morphinandienones with the flavinan-tine orientation of substituents (148). Attempts to obtain the isomeric 3,4,6-substitution pattern of salutaridine by use of 6 -bromo-compounds failed, the bromine atom being removed, and 6 -chloro-compounds suffered cleavage. ... 

Many hydantoins are endowed with significant pharmacological activities as highlighted by 5,5-diphenylhydantoin (Dilantin ), an anticonvulsant and antiepileptic discovered by Parke-Davis in 1940 s. Despite the lapse of more than half a century, Dilantin still plays an important rote in modem medicine. Meanwhile, another anticonvulsant 15 was synthesized from 9,10-dimethoxy-l,3,4,6,7,llb-hexahydro-pyrido[2,l-a]isoquinolin-2-one (14) under the standard Bucherer-Lieb variation in a 2 1 water-ethanol solution (15a 15b = 8 l). ... 

The mass spectral fragmentations of 9,10-dimethoxy-2,3,4,6,7,ll/)-hexa-hydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140 and -2,4-diones 141, under electron ionization (at 70 eV) were examined by metastable ion analysis, a collosion-induced dissociation technique and exact mass measurement (97RCM1879). Methyl substituent on N(3) in 140 (R = Me) had a larger effect on both the fragmentation and on the peak intensities, than a methyl substituent on C(6) (R = Me). The ionized molecules of 140 (R = H) were rather stable, whereas 4-phenyl substitution on C(4) of 140 (R = Ph) promoted the fragmentations of the molecular ions. The hexahydro-1//-pyrimido[6,l-n]isoquinoline-2,4-diones 141 were more stable, than the hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140, and the molecular ions formed base peaks. 

Aryloxy-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones formed in the reaction of 2-chloro derivative and phenols in the presence of K2CO3 in DMF at 90 °C for 2. 5 h or in boiling 2-PrOH for 6-24 h (00MIP20). When 2-isobutylphenol was used the reaction was carried out in the presence of BuLi in THF at —78 °C. 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

Chemical Name 1(4-ethoxy-3-methoxybenzyl)-6,7-dimethoxy-3-methyl isoquinoline phosphate... 

To a solution of 50 grams of 6,7-dimethoxy-3-methyl-T(4 -ethoxy-3 -methoxybenzyl)-dihy-droisoquinoline base in 200 ml of dry benzene are added 150 ml of decalin, and the mixture is distilled until its temperature reaches 180°C. 1.5 grams of 5% palladium on carbon are then added. The mixture is stirred under reflux for about 6 hours to dehydrogenate the dihydroisoquinoline. On cooling, the reaction mixture is diluted with petroleum ether and the precipitated 6,7-dimethoxy-3-methyl-1-(3 -methoxy-4 -ethoxybenzyl)-isoquinoline is filtered off and recrystallized from dilute ethanol. 

B. 2-Acetyl-6,l-dimethoxy-l-methylene-l,2,3,4-tetrahydroisoquinoline [Isoquinoline, 2-acetyl-l,2, A,4-tetrahydro-6,7-dimethoxy-l-methylene-]. A 1-1., three-necked, round-bottomed flask equipped with a mechanical stirrer, a reflux condenser topped with a calcium chloride drying tube, and a thermometer is charged with 110 ml. of acetic anhydride, 110 ml. of pyridine, and 45.0 g. (0.22 mole) of the dihydroisoquinoline prepared in Part A. The reaction mixture is stirred and heated at 90-95° for 30 minutes, stored at room temperature overnight, and concentrated by distillation at 50° using a rotary evaporator. The residue is diluted with 20 ml. of ethyl acetate, and another evaporation under reduced pressure gives material that can be crystallized from 75 ml. of ethyl acetate to yield 38.5 41.0 g. (72-77%) of product, m.p. 106-107° (Note 11). 

Isoquinoline, 2-acetyl-l, 2,3,4-tettahydro-6,7-dimethoxy-l-inethylene-, 4 Isoquinoline, 2-benzoyl-l -benzy 1-1-cyano-1,2-dihydro- [1-Isoquinolinecarbo-mtrile, 2-benzoyl-l, 2-dihydro-l -(phenjlmethyl)-), 23 Isoquinoline, 2-benzoyl-l -cyano-1,2-di-hydro l-Isoquinohnecarbomtrile, 2-ben2oyl-l, 2-dihydro-], 20 ISOQUINOLINE, 1-BENZYL- [ISOQUINOLINE, HPHENYLMFTHYL)-], 19 Isoquinoline, 3,4-dihydro-6,7-dimethoxy-l-methyl-, 4... 

RN 10539-19-2 ME C20H21NO2 MW 307.39 EINECS 234-117-5 CN 3-ethyl-6,7-dimethoxy-l-(phenylmethyl)isoquinoline... 

Cyclization occurred at the N-3 atom when 4-(3-bromopropylaruino)-l, 6,7,1 1 b-tctrahydro-2//-pyrimido[6,l -zz -isoquinoline was treated with NaH to give a tetracyclic derivative <2003M1271>. 9,10-Dimethoxy-2-(arylimino)-2,3,6,7-tetrahydro-4//-pyrimido[6,l- ]isoquinolin-4-ones were N-3-alkylated with iV-(ra-bromoalkyl)phthalimides in the presence of K2C03 and a catalytic amount of I2 in boiling 2-butanone in 13-67% yields <2000W020/058308>. Treatment of the 2-[(4-methoxyphenyl)methyl] derivative of 2,3,6,7-tctrahydro-l //,5//-pyrido[3,2,l-/ylqninazolinc-... 

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