3.4- Dimethoxyphenyl- -ethylamine

A-Acetylhomoveratrylamine2 is prepared by adding 190 ml. of acetic anhydride to a stirred solution of 300 g. (1.80 moles) of /3-(3,4-dimethoxyphenyl)ethylamine [Benzeneethanamine, 3,4-dimethoxy-J (Aldrich Chemical Company, Inc.) in 150 ml. of pyridine at such a rate that the temperature is maintained at 90-95° (ca. 1.5 hours is required). After the solution has been stored at room temperature overnight, the volatile material is evaporated under reduced pressure, and the residue is crystallized from ethyl acetate to give 286-306 g. (78-83%) of acetylated product, m.p. 99-100°. 

Dobutamine (76), on the other hand, is a dopamine derivative which does not act centrally, but is of interest because of its coronary vasodilator properties. Such drugs are potentially of value in treatment of angina pectoralis. Further, it is now undergoing extensive clinical trials as an inotropic agent for use in heart failure. Its synthesis is effected by Raney nickel catalyzed reduction of methyl p-methoxyvinylphenylketone (75) to its dihydro analog followed by reductive alkylation with p-(3,4-dimethoxyphenyl)ethylamine. The ether groups are cleaved with HBr to complete the synthesis of... 

Intermediate diketopiperazine derivatives have been employed in the diastereoselective synthesis of benzyltetra-hydroisoquinoline by 1,4-chirality transfer. iV-Cbz-Proline was coupled with 2-(3,4-dimethoxyphenyl)ethylamine and the resulting amide 109, after deprotection, was reacted with phenylpyruvic acid (Cbz = carbobenzyloxy group). Compound 110 underwent acid-catalyzed Pictet-Spengler condensation to yield final tetracyclic... 

The reactions of 2-(3,4-dimethoxyphenyl)ethylamine hydrochlorides with the sodium derivative of diethoxycarbonylglutaconate (8, R = H) in refluxing ethanol afforded the corresponding aminomethylenemalonates (357) in 84-885 yields (56JOC336). 

Trichocereus pachanoi Cactus Mescaline 3,4-dimethoxyphenyl- ethylamine 3-methoxy-tyramine... 

Dopamine As a medicinal agent, dopamine, 2-(3,4-dihydroxyphenyl)-ethylamine (11.3.1), is synthesized by demethylation of 2-(3,4-dimethoxyphenyl)ethylamine (19.4.3) using hydrogen bromide [49-51]. 

The first homopavine, ( )-homoargemonine (174), was synthesized in 1973 in an attempt to construct pavine analogs with improved analgesic activity (Scheme 38) (777). The corresponding 1-phenethylisoquinoline 173 was obtained by a Bischler-Napieralski condensation of 2-(3,4-dimethoxyphenyl)-ethylamine (170) and 3-(3,4-dimethoxyphenyl)propionic acid (171) via the hy-droxyamide intermediate 172. Compound 173 was then successively quater-nized, reduced by lithium aluminum hydride, and treated with acid to afford the tetracyclic compound ( )-174. 

An attempt to utilize this conversion of amines into aldehydes in an isoquinoline synthesis was not successful.439 Instead, reaction between 2-(3,4-dimethoxyphenyl)ethylamine and isatin afforded only the spiro compound 150.439 Reaction between isatin and 2-(3-hydroxy-4-methoxyphenyl)ethylamine gave a mixture of two spiro compounds, while a reaction of isatin, this amine, and benzylamine gave 6-hydroxy-7-methoxy-l-phenyl-1,2,3,4-tetrahydroisoquinoline.439... 

To a suitable reactor under a nitrogen blanket is added 13.7 kg of p-(3,4-dimethoxyphenyl)ethylamine. The amine is cooled to 5°C and 12.5 kg of 3-(m-tolyloxy)-l,2-epoxypropane is added maintaining the temperature between 5-10°C. After 10 hours, the mixture is seeded with bevantolol free base seeding is repeated approximately every 2 hours until it is evident that crystallization has started. After stirring for 48 hours at 10°C, 26 L of hexane is added. The temperature is raised to 25°C and stirring is continued for 48 hours. The slurry is filtered and the collected solid is dried under vacuum. The product is dissolved in 60 L of isopropyl alcohol and the solution is filtered. 

To a stirred solution of p-(3,4-dimethoxyphenyl)-ethylamine (100 g, 0.552 m) and triethylamine (66.6 g, 0,66 m) in CHCI3 (1 liter) was added acetyl chloride (47.1 g, 0.60 mole) dropwise over a period of 30 min and the mixture stirred overnight. The mixture was washed with 3x500 ml H20, dried over MgS04 and evaporated to a solid. The solid was dissolved in 500 ml hot CCI4, 300 ml cyclohexane added and allowed to cool slowly. The crystallized solid was collected by filtration and dried to afford N-acetyl-3,4-dimethoxyphenethylamine as a white solid, 112.1 g (91% yield). MP 99-100°C. 

Dimethoxyphenyl)ethylamine Phosphorusoxychloride Sodium borohydride Benzeneacetic acid, 4-nitro-Dicyclohexylcarbodiimide... 

When these approaches proved unsuccessful, a total synthesis of erysotrine was finally achieved beginning with the oxalyl derivative (LIT) of 4-methoxycyclohexanone. The synthetic scheme has so far been reported only in preliminary communications 27, 36). The condensation with -(3,4-dimethoxyphenyl)-ethylamine leading to the tetracyclic erythrinane skeleton and the further conversion to LV have been discussed in Section III, C (Fig. 8) the remainder of the synthesis is outlined in Fig. 10. 

N-Acyliminium ion-mediated Pictet-Spengler reaction has also been applied to the synthesis of tetrahydroisoquinolines [404]. Thus, supported 4-formylbenzoic acid (569) was reacted with 2-(3,4-dimethoxyphenyl)ethylamine (570), affording the corresponding resin-bound imine (571). The latter underwent N-acyliminium ion-mediated Pictet-Spengler condensation in the presence of a number of acid chlorides, sulfonyl chlorides, and a chloroformate under basic conditions to give (572) better yields and purities were obtained using acid chlorides and the chloroformate (Scheme 119). 

Our first attempt was an enantioselective synthesis of (k)-(+)-carnegine [7,8]. Michael addition of 2-(3,4-dimethoxyphenyl)ethylamine (7) to (R)-(+)-l took place readily at room temperature in chloroform (Scheme 5). Without isolation of any intermediate, the reaction mixture was treated with excess trifluoroacetic acid to effect the cyclization. Depending on the reaction conditions and the aryl substituent of the chiral sulfoxide, different levels of diastereoselectivity were observed. The results are summarized in Table 1. Under proper conditions (TFA, 0°C, 4h), 10b could be obtained in 65% yield as the only isolated product (Scheme 5) (Table 1). 

Reaction of 3 with 2-(3,4-dimethoxyphenyl)ethylamine (4) afforded the amide 5 (91 %), whose cyclization gave 6, which was converted, via 7, to the diastereomers 8 and 9 in a ratio of 13 87. The predominant epimer 9 was treated with sodium methoxide to give 10,... 

Starting from ) (3,4-dimethoxyphenyl)ethylamine (X) the following reactions were carried out to synthesize the natural product ( )-camegine (E) ... 

N-Benzoyl-2-(3, 4 -dimethoxyphenyl)ethylamine treated 18 hrs. at room temp, with monochloromethyl ether in glacial acetic acid 2-benzoyl-6,7-dimethoxy-l,2,3,4-... 

Dimethoxyphenyl)ethylamine and 4 eqs. NEt3 added to a soln. of 6,7-dimethoxy-1 -methyl-3-[(Xmethylphenylsulfonyl)oxy]-4-nitroisoquinoline in toluene, and refluxed under N2 for 12 h - 6,7-dimethoxy-3-[2-(3,4-dimethoxyphenyl)ethyl]-amino-l-methyl-4-nitroisoquinoline. Y 91%. F.e. and conversion to 3,4-diantinoiso-quinolines s. J.S. Hinkle, O.W. Lever, Jr., Tetrahedron 44, 3391-8 (1988). 

A soln. of startg. diketoester in benzene and 2-(3,4-dimethoxyphenyl)ethylamine treated with trifluoroacetic acid with exposure to air product. Y 71%. F.e. and aromatization s. H.H. Wasserman et al., Tetrahedron Letters 30, 869-72 (1989) l,2,3,4-tetrahydropyrid[3,4-6]indole ring s. ibid. 873-6. 

Takesada, M., Kakimoto, Y., Sano, I. and Kaneko, Z., 3,4-Dimethoxyphenyl-ethylamine and other amines in the urine of schizophrenic patients, Nature 199,203 (1963). 

Acetaldehyde added to a soln. of l,2-bis-(3,4-dimethoxyphenyl)ethylamine in aq. 6 N H2SO4, refluxed 1 hr., more acetaldehyde added to the cooled soln., allowed to stand overnight, a third portion of acetaldehyde added, and refluxed 5 hrs. 3-(3,4-dimethoxyphenyl)-l,2,3,4-tetrahydro-6,7-dimethoxy-l-methyliso-quinoline (Y 74%) dissolved in aq. acetic acid, treated with mercuric acetate, gently warmed until dissolved, refluxed 9 hrs., mercurous acetate removed by filtration, Hg removed with HgS, and the product purified via the hydrogen oxalate 3-(3,4-dimethoxyphenyl) -3,4-dihydro-6,7-dimethoxy-l-methylisoqui-noline (Y 71%). A. R. Battersby and R. Binks, Soc. 1958, 4333. 

The formation of substituted isoquinolines was achieved by E. Awuah and A. Capretta. In the first step an amine reacted with an aryl acetic acid in POCI3 and toluene under microwave (MW) irradiation at 140°C for 30 min to afford 2-(3,4-dimethoxyphenyl)ethylamine (92). Subsequent oxidation of tetrahydroisoquinolines 92 with air using Pd/C in toluene led to the final products, acylisoquinoline derivatives 93 (Scheme 34) (10JOC5627). 

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