SU765268A1 - 3,4-dihydropyrrolo-/1,2-alpha/-pyrazine as intermediate product for the synthesis of physiologically active compounds and its preparation method - Google Patents

Description

environmental active compounds.

This is achieved by a new 3,4-ahydro pyrrole o- (1,2-a) -pyrazine of formula

OL

kx.

The method of obtaining 3.4 dihydropyrrolo- (1 2-) - pyrazine consists in the fact that dialkylacetal or dioxolane 2,5-dialkoxytetrahydrofurfurol in an organic acid is reacted with ethylene diamine at 100-150 ° C, with an atom of ethylenediamine-h reacting with atom one 2,5-dialkoxytetrahydrope with a furan system to form a pyrrole system, while the second amino group of ethylenediamine reacts with an acetal or dioxol group to form a Schiff base. Synthesis of 3,4-1-hydropyrro (1,2-e) -pyrazine proceeds according to the scheme:

.sn41z, nn

UiO

OY1

where a), j R3 a 6), H5

fe) T-CH3-, R2 3 2 2 Theoretically, in the claimed process, one mole of acetal or dioxolane 2,5-dia-L-alkoxytetrahydrofurfurol reacts: With one mole of ethylenediamine. However, in order for the process to proceed more smoothly, it is recommended to take a small excess of ethylene diamine (0.2-0.5 mole).

Practically the most convenient organic acid is acetic acid. The ratio of the amounts of the starting materials to the amount of acetic acid can be varied within wide limits (from 1: 3 to 1:15 or more), and the ratio of 1: 5 is optimal. The process is preferably carried out in the presence of 0.5-2 moles of water per mole of ethylenediamine.

Isolation of 3,4-dngidropyrolo- (1,2-a)

α-pyrazine from the reaction mass is carried out by a known method by distilling the acid followed by alkalinization.

residue and extraction of the reaction product with an organic solvent. After distillation of the solvent and distillation, the target product is obtained in the form of a colorless mobile liquid with an amine odor,

3,4-Dihydropyrrolo- (1,2-a) -pyrazine is a colorless liquid with an amine odor, m.p. 9294 C / 8 mm Hg. Art., P 1.5945. The structure of the obtained substance was confirmed by elemental analysis data, PMR, and mass spectra. In the PMR spectrum, there is a singlet at 3.80 m, d (scale S, internal standard TMS), corresponding to four runs at C and Cd atoms; multiplet in the range of 6, OO-6.37 ppm, corresponding to two protons at C and Cg atoms; multiplet centered at 6.60 ppm, corresponding to one channel

. with S .; singlet at 8.07 m, d., corresponding to one proton at C atom. The integral curve corresponds to a total of eight protons, and its form corresponds to the proposed formula of matter. The individuality of the substance was proved by the gas chromatographic method, and its molecular weight was determined from the data of the mass spectrum, according to which M has th / e

120

The resulting 3,4-dihydropyrrolo- (1,2-a) -pyrazine can be used as an intermediate product for the preparation of drugs.

5 nonahlazina and azabutiron. Thus, from 3,4-dihydropyrrolo- (1,2-a) -pyrazine, when reduced by hydrogen in the presence of catalysts, under mild conditions: octagicropyrrolo- (1,2-) can be obtained at room temperature and atmospheric pressure in high yield. a) pyrazine.

The advantage of using 3,4 dihydropyrrolo- (1,2-a) -pyrazine as an intermediate product is the possibility of carrying out the process of obtaining octahydropyrro- (1,2-a) -pyrazine under mild conditions, which can be carried out on an industrial scale. At the same time, a dialkyl acetal or dioxolane of 2,5-dialkosi, tetra; hydrofurfurol, which is obtained from available furfurol, is used as a raw material for the preparation of 3,4-dihydropyrrolo- (1,2-a) -pyrazine.

Example 1. To a mixture of 20.6 g of dimethyl acetal 2,5-dimethoxytrahydrofurfurol and 8.2 g of a 86% ethylenediamine aqueous solution, 100 ml of glacial acetic acid are added dropwise with cooling and stirring. The reaction mass is heated at 100 for 2 hours. The acetic acid is distilled off in vacuo, the residue is dissolved in 20 ml of water and alkalinized with an aqueous 20% caustic soda solution to the alkaline medium. The product is extracted with benzene. The benzene is distilled off, the residue is distilled in vacuo. 9.9 g (82%) of 3,4-dihydropyrrolo- (1,2-a) -pyrazine are obtained, t. Bale. 92-94C / 8 mm Hg. Art., 1.5945. Found,%: C 69.91, 69.60; H 6.80, 7.04; N 23.45, 23.59. With HgW. Calculated,%: C 69.95; H 6.71; H 23.31. Example 2. According to the method of example 1, 3,4-dihydropyrrolo- (1,2-a) -pyrazine is obtained in a propionic acid medium at 120-15O ° G in 61% yield. Example 3. According to the procedure of Example 1, 3,4-ahydropyrrolo- (1,2-a) -pyrazine and diethyl acetal 2,5-diethoxytetrahydrofurfurol are obtained in a yield of 70%. Example 4. To a mixture of 5.1 g of Dio Salan 2,5-dimethotetrahydrofuryl 4 hours, 1.8 g of 100% ethylene diamine and 0.3 g of water, with stirring and cooling, add 25 ml of glacial acetic acid. The reaction mass is heated at 12 ° -14 ° C for 2.5 hours. Acetic acid is distilled off in vacuo, the residue is dissolved in 5 ml of water and alkalinized with 20% sodium hydroxide solution to an alkaline medium. The product is extracted with benzene. The benzene is distilled off, the residue is distilled in vacuo. 2.3 g (77%) of 3,4-dngipropyrolo (1,2-a) are obtained. pyrazine Formula for obtaining 1. 3,4-dihydropyrrolo- (1,2-a) -pyrazine of the formula O. II II t fl As an intermediate product for the synthesis of physiologically active compounds. 2. A method for producing a compound according to claim 1, characterized in that the dialkladatetal or dioxolane 2,5-aryalkoxytetrahydrofurfurol is reacted with ethylene diamine in an organic acid at 1OO-15O C. 3. The preparation method according to claim 2, wherein the process is t in the presence of 0 to 5 - 2 moles of water per mole of ethylenediamine. Sources of information taken into account during the examination 1. USSR author's certificate No. 352877, cl. C 07 D 471 / O4, published 1972. 2. USSR author's certificate number 459229, cl. A 61 K 27 / OO, publ. 1975. 3. Ponomarev, A.A., et al. Catalytic Synthesis of 7-aaaoctagidropyrrololines, DAN, 1963, V. 148, N9 4, p. 86O, 4.Nazarova, L.S., et al. Synthesis and Certain Transformations of 1,4-diazabicyclo- (4.th.d.) —HCF alkanes, 1976, No. 1, p. 88

Claims (3)

Claim 1. 3,4-dihydropyrrolo- (1,2-a) -pyrazine of the formula as an intermediate for the synthesis of physiologically active compounds. 2. A method for producing a compound according to π. 1, characterized in that the dialkyldetal or dioxalane The 2,5-dialkoxytetra of hydrofurfural is reacted with ethylenediamine in an organic acid at 100-150 ° C. 3. The production method according to p. 2, characterized in that the process is carried out in the presence of 0.5 to 2 moles of water per mole of ethylenediamine.