SU798104A1 - 1,2,3,4-tetrahydropyrrolo-(1,2a)pyrazine as intermediate product for synthesis of physiologically active substances and its preparation method - Google Patents

Description

The invention relates to the synthesis of 1,2,3,4-tetragyaropyrrolo (1,2-a) pyrazine, which can be used as an intermediate product for the synthesis of physiologically active substances, for example, the neuroleptic azabutyron, a corona-expanding drug nonahlazine and cp, lj and For the synthesis of azabutyron and nonahlazine, in the known methods, octahyd ropyrrolo (1,2-e) pyrazine is used, which is obtained by catalytic dehydration of furan diamines in a quartz tube at ZOO-315 C over aluminum oxide activated with carbon dioxide (yield of the target product is about 30% ), as well as the reduction of hexahydropyrrolo (1,2-a) pyraain-1-one with lithium aluminum hydride in ether medium. Hexahydro-pyrrolo (1,2-a) pyrazin-1-one is obtained by multistage synthesis from the hard-to-reach S-chloro-valeric acid, including bromination with O-chloro-Valerianic acid with bromine in the presence of PCE, ethirifying the resulting product and subsequent condensation with ethylene diamine 3J and 4J. The disadvantages of the methods are the difficulty of their implementation on an industrial scale, the multi-stage process, the low yield and the need to use hard-to-reach raw materials. The purpose of the invention is the synthesis of 1,2,3,4-tetrahydropyrrolo (1,2-a) pyrazine, the use of which as an intermediate product makes it possible to obtain the indicated preparations as well as their analogues in a simpler and more convenient way. This goal is achieved 1,2,3,4-tetrahydropyrrolo - (1,2-a) pyrazine of the formula: The method of obtaining 1,2,3,4-tetrahydropyrpo (1,2-a) pyrazine is

in that it is subjected to the reduction of 3,4-cygiaropyrrolo {1,2-a) pyrazine of the formula

l /

ABOUT.

The reduction is preferably carried out by catalytic hydrogenation over noble metal catalysts at room temperature and atmospheric dansing or reduction is carried out with complex metal hydrides.

As catalysts from noble metals, platinum or palladium catalysts can be used, and potassium borohydride or aluminum alumina lithium can be used as complex metal hydrides. In the case of potassium borohydride, the reduction is carried out in an aqueous-alcoholic medium. When lithium aluminum hydride is used, 80001-8 renewal is carried out in the essential solution. To isolate 1,2,3,4-tetrahydropyrrolo {1,2-a) pyrazine from the reaction mixtures after reduction, known methods are used:

in the case of using the method of catalytic reduction with hydrogen of kata. 0

U,

It

The use of 1,2,3,4-tetrahyaropyrrolo (1,2-a) pyrazine makes it possible to obtain a high yield of octahydropyrrolo (1,2 - ") pyraine in a simpler and convenient way, which can be carried out under industrial conditions using the quality of the original product available furfural.

Examples of 1,2,3,4-tetrahydropyrrolo (1,2-a) pyrazine psh-radiation.

Example 1. 1,2,3,4-tetrahyaropyrrolo (1,2-a) pyrazine.

36 g of 3,4-dihydropyrrolo (1,2-a) pyrazind in 25 O ml of absolute methanol. hydrated over 1 g of 1O% - «th P jf BagOj The theoretical amount of hydrogen is

the lyser is filtered off, the solvent is distilled off and the residue is distilled in vacuo;

upon reduction with potassium borohydride, the reaction product is extracted with benzene,

benzene is distilled off and the residue is distilled in vacuo;

when reduced by lithium aluminum hydride, the reaction mass is decomposed by water and aqueous alkali solutions for

destruction of excess lithium aluminum hydride, then the reaction product is extracted, the solvent is distilled off, the residue is distilled in vacuum.

Allocation can be made

and other methods used to isolate organic matter: tera.

The structure of the obtained substance is confirmed by elemental analysis data of the base and salts, by NMR spectra.

1,2,3,4-tetrahydropyrrolo {1,2-a) pyrazine can be used as an intermediate product for the synthesis of octahydropyrrolo {1,2-a) pyrazine, a,

therefore, physiological active substances derived from it, for example, nonahlazine and azabutiron.

The synthesis of octahydropyrrolo (1,2-a) pyrazine using 1,2,3,4-tetrahydropyrrolo (1,2-a) pyrazine is carried out according to the scheme

OR OR

cw o / g

V

.

polished for 3 hours. The catalyst is filtered off, the methanol is distilled off, the residue is ground in vacuo, the fraction is collected under vacuum, and the ions qj TL-jnlOO-lOl C / mm Hg. Art. with 34 g (95%); 1.553 Output

Elemental analysis:

Calculated,%: C 68.82; - H 8.25.

.

C 68.40-68.49; H 8.15 Found,%: 8.13.

Maleate is obtained by pouring out alcoholic solutions of the base and maleic acid (mole ratio 1: 1.1). T.- 151-15243 (from aqueous alcohol).

Claims (4)

Elemental analysis: Calculated D: C 55,46; H 5.92; N 11.76, Nayeno,%: C 55.50-55.76; H 6.04-6.06; N11.91-. 1.78. Example 2. 1,2,3,4-tagrygidro pyrrolo (1,2-a). Pyrazin. 3,4-di-aryopyrxo (1,2-a) pyrazine is obtained by firing in absolute methanol over platinum oxide. The isolation was carried out according to the procedure described in Example 1. The yield was 92%. Example 3. 1,2,3,4-tetrahydro pyrrolo 1,2-a) pyrazine. A solution of 6 g of 3,4-dihydropyrrolo (1,2-a) pyrazine in 30 ml of absolute alcohol is mixed with a solution of 5.4 g of potassium borohydride in 30 ml of water and with 15 drops of 10% caustic. The mixture is kept at room temperature for 2 hours. temperature and then heated for 2 hours in a boiling water bath. The product is extracted with benzene. The solvent is distilled, the residue is distilled in vacuum, collecting the fraction with T 100-1 / 7 mm Hg. Art. Yield 5.2 g (85%); P 1 ,. Example 4. 1,2,3,4-tetrahydropyrrolo (1,2-a) pyrazine. To a suspension of 2.28 g of lithium aluminum hydride in 5O ml of absolute, 3.6 g of 3,4-dihydropyrro (1,2-a) pyrazine is added dropwise to 50 ml of absolute ether. The mixture was boiled for 2 hours, and the reaction mass was decomposed by sequential addition of 2.3 ml of water; 1.68 ml of 40% caustic soda and 8 ml of water. The mixture is boiled for 15 minutes, the ethereal solution is separated by decantation. The ether is distilled off, the residue is evaporated with benzene and distilled in vacuum, collecting the fraction c. 10O-101 C / 7 mm Hg. Art. Yield 3.2 g (87%); 1.5522. 46. Claims of the invention 1. 1,2,3,4-tetragitsiro11irrolo (. 1,2-a) pyrazine of the formula kxfiH as an intermediate product for the synthesis of physiologically active substances. 2. A method of producing compounds according to claim 1, characterized in that it is subjected to selective reduction of 3,4-dihydropyrrolo (1,2-a) pyrazine of formula 3. The method according to claim 2, characterized in that the reduction is carried out by catalytic hydrogenation over noble metal catalysts at room temperature and atmospheric pressure. 4. A method according to claim 2, characterized in that the reduction is carried out with complex metal hydrides. Sources of information taken into account during the examination 1. USSR author's certificate 352877, cl. C 070471 / O4, 1972. 2. Authors certificate of the USSR S 459229, cl. A 62 K 27 / GS, 1975. 3.Ponomareva, A.A., et al. Catalytic synthesis of 7-azaooctagidropyrrocroles. DAN, 1963, No. 4, Vol. 148, p. 86O. 4.Nazarova L.S. and others. Synthesis and some transformations of 1,4-diazabicyclo 4, t, 0) alkanes. HFZh, 1976, No. 1, p. 88