SU988192A3 - Process for preparing tricyclic compounds - Google Patents

Description

(5) METHOD FOR OBTAINING TRICYCLIC COMPOUNDS

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The invention relates to a method for producing non-described tricyclic compounds of the general formula

AilTRiBa

where A is a simple bond or alkylene

with 1-5 atoms of ulerod, in position 2 or 3;

A2 is alkylene with 1- carbon atoms; Aa is a simple bond or alkylene to

1-3 carbon atoms; X is oxygen or sulfur, one of R and Rj is hydrogen or R and R are independently of each other alkyl with 1-5 carbon atoms, aralkyl with carbon atoms, alkoxycarbonyl with 2-5 carbon atoms, alkanoyl with 2-5 carbon atoms, haloalkanoyl with 2-5 carbon atoms or benzyloxy5 carbonyl, possessing pharmacological activity,

Famous co-sobsbb secondary or tertiary amines, as well as

10 amides of carboxylic acids, which imply that the amine is reacted with organic halogenium or an ester, an acid chloride and a carboxylic anhydride 5, respectively.

The purpose of the invention is to develop a method for producing new pharmacologically active three cyclic compounds.

20 of the general formula 1.

This goal is achieved by the method of obtaining tricyclic compounds of general formula 1, which consists in the fact that the compound is general formulas where X and R have the indicated meanings, is subjected to interaction with the compound of the general formula .g | d, where Cs takes the values R, kro hydrogen, Z - halogen, alkanoyloxy or hydroid-alkanoyloxy, and, and a compound of the general formula D2 enHi where, X and R2 have the indicated meanings, are reacted with a compound of the general formula "4 where Z has the indicated meanings, R takes the values R, ch: hydrogen, or compounds general formula wherein AA ,, X and Z have the abovementioned meanings, are reacted with amines of the general formula wherein R. R., and RQ are defined as significant in an inert solvent at the round from 0 ° C to the solvent reflux temperature. The process is preferably wire. in the presence of an organic base, e.g. sodium methoxide, potassium t-butylate, triethylamine, pyrene, dimethylaniline, or an inorganic base, e.g. sodium hydride, caustic soda, caustic potassium, sodium carbonate, potassium carbonate, sodium bicarbonate. Benzene, toluene, tetrahydrofuran, ether, dimethoxyethane, methanol, and ethanol are used as inert solvents. Tricyclic compounds of general formula 1 have antiviral effect in combination with relatively low toxicity. Example: To a solution of 21.5 g of diethylmethylenemalonate in 200 ml of benzene, 9.8 g of cyclopentadiene is added at room temperature. The reaction mass is stirred at this temperature for one hour. After evaporation of the solvent by distillation of the residue, 11.8 g of 2,2-bis-ethoxycarbonyl-5-porbornene are obtained. The boiling point of the product at 0.2 mm Hg. 85-90 ° C. IR spectrum (film): 2970, 1460. Repeat the same procedure, but using g diethylmethylenemalonate and 20 g 1.3 diclohexadiene and boiling benzene under reflux, get b5 g oily 2.2 -bis-et-oxycarbonylbicyclo 2,2,2 oct-5-ene. IR spectrum (film, cm: 2970,.. Following the same procedure, but using 8.3 g of itaconic anhydride and 10 g of 1,3-cyclohexadiene and subjecting benzene to refluxing benzene, 10.5 g of solid exo- 2-carboxyendo-2-carboxymethyl anhydride bicyclo 2,2,2-oct-5-ene. Mp 70-75 ° C (after recrystallization from hexane). IR spectrum (KBr, cm-H): 2950, 1850, 1780, 1240, 1030.; Following the same procedure, but using 35 g of methyl alpha-cyano-acrylate and 28 g of cyclopentadiene, 56 g of oily exo-2-cyano-endo-2-methoxycarbonyl-5 carborne | ea are obtained. This product contains 1001 and Exo-2-methoxycarbonilendo-2-cyano-5-norbornene zomers Infrared film film, cm-: 2960, 2230, 1750, 1320, 1250. Following the same procedure, but using methyl alpha-cyanoacrylate (20 g) and 1,3-cyclohexadiene (k, k g), get 33 g of oily exo-2-cyano-endo-2-methoxycarbonylbicyclo-C2,2,2} oct-5-ene. The product contains 20% of the exo-2 isomer -methoxycaronono-2-cyanobicyclo 2,2.2-oct-5 en IR spectrum (film, cm): 2950, 2250, 1750, 1270, 1260, 1080. Example2. For an hour, a mixture of 12 MP methyl alcohol, aqueous sodium hydroxide, 12 ml of tetrahydrofuran and 2.38 g of 2,2-bis-ethoxycarbonyl-5-norbornene is stirred at room temperature, and then this mixture is concentrated under reduced pressure. The residue is diluted with water, acidified with hydrochloric acid (no), and extracted with ether. The extracts are washed with water and dried. Removal of the solvent gave 1.63 g of oily 2,2-dicarboxy-5-norbornene. IR spectrum (film, cm); 2990, 1710, .. Following the same procedure and using the quality of the initial reagents, the products of example 1 are obtained after blowing compounds; 2,2-Dicarboxybicyclo 2.2.2 oct -5-ene, oily substance, IR sinter (film, 2990, 1710, 1350. Exo-2-cyanoendo-2-carboxy-5-norbornene, oily substance. IR (film, cm): 2980, 2bOO, 22ftO, 1720. Exo-2-cyanoendo-2-carboxybicyclo 2,2,2-oct-5-ene, mp 129-130 ° IR spectrum ( KBr, cm: 2980, 2230, 1700. Approx 1.63 2.2-dicarboxy-5-norbornene is dissolved by heating in 0.5N sodium bicarbonate solution (60 ml). After cooling to room temperature, add a solution of iodine (2.5 g) and iodide cale (5.08 gU in 30 ml of water. The mixture is left in the dark for 2 h, then filtered, filter T is acidified with dilute hydrochloric acid HC1 and treated with sodium thiosulfate until the iodine disappears. Then extracted with ether, the extract is washed with a saturated solution of sodium chloride and dried. After removing the solvent, a substance is obtained which is recrystallized from benzene. 5-oxa - + - oxo-3 carboxybrendan, mp 171-172 C. IR spectrum (KBG, cm-): 2950, 1780, U80, Following the same procedure and using as initial reagents the products of example 2 , is obtained following the compound: Exo-10-iodo-5-oxa-oxo-3 carboxy otvistan m.p. 198-200 C (after recrystallization from benzene), IR spectrum (KBG, 2950, 1780, 1710, 1380., Exo-9 iodo-5 oxa-4-oxo-3 Cyanobrendan with mp, 5 ° С ( after recrystallization from benzene). IR spectrum (Nujol, cNf): 2250, 1780, 11 1100. Exo-10 iodo-5-oxa-oxo-3 cyanoisotvistan, with a melting point of 178-179 ° C (after recrystallization from benzene - Sulfuric ester.) IR spectrum (Nujol, cm-): 2250, 1790 .. Following the same procedure and using as starting reagents, compounds prepared according to the procedure of Example 1, the following compounds are prepared: Exo-11 -iodo-6-oxa-5-oxo-3-carboxylhomozovistan mp 205210 ° C (after recrystallization from sulfuric ether). IR spectrum (film, cm-): 1720,, 1300. According to the same procedure, exo-1.0-iodo-5-oxa-4- oxo-endo-2-carboxy-isotvistan with m.p., 191 193 ° C. IR spectrum (Nujol): 1790. 1780, 1730, 1710. Example. For 3 h, ki, t t under reflux mixture 1 g of exo-9-iodo-5-oxa-4-oxo-3-carboxybrentane and 20 ml of chloro-pure thionyl. The reaction mixture is evaporated to dryness, 20 ml of benzene is added to the residue and evaporated to remove 4 chloro-thionyl. To a solution of the acid chloride obtained in acetone (20 ml), 0.232 g of sodium azide is added with cooling. The reaction mixture is stirred for 2 hours at room temperature. After evaporation of the solvent, the residue is dissolved in 50 ml of dry ethyl alcohol and refluxed for 2 hours. After evaporation of the solvent, the residue is extracted with chloroform. The extract is washed with water and dried. By evaporation of the solvent, a solid is obtained, which, after recrystallization from benzene, yields 0.85 g of exog9-iodo-5-oxa-. -t-OKCo-3-ethoxycarbonylaminobrendan with mp. 1b5-1b7 ° C. IR spectrum (KBG, cm--): 3320, 2990. 1800, 1690. Following the same procedure and using - as starting reagents, the products synthesized in accordance with the procedure of example 3 obtain the following compounds: Exo-10 - iodo-5-oxa-A oxo-etoc sicarboni aminoisotwistan. IR spec (Nujol): 3350, ISOO, 1730-170 15 + 0-1510. Exo-10-iodo-5-oxa-4-oxo endo -2-ethoxycarbonylaminoisotwistan with so pl. 15B-159 C after recrystallization from a mixture of ethyl acetate - n-hexane. JK Spectrum (Nujol, cm-): 3300, 1800, 1690, 1550., Exo-11-iodo-6-oxa-5-oxo-3 is sycrono-aminogamootvistan (18, pp. 13E-1 0 ° C. The IR spectrum (Nujol 3300, 1720, 1530. Exo-10-Iodo-6-oxa-5-oxo-3 is a sicarbonylaminobrendan with mp 1, 5 ° C. IR spectrum (Nujol, cm): 3350, 1730-1700, 1450. Example 5, To a solution of k, S g of exo-9thiodo - $ - oxa-4-oxo-3-ethoxycarbonylaminobrendan and 50 mg of azobisisobutyronitrile in 100 ml of dry tetrahydrofuran are added 4.5 n-trihydride butyl tin in 50 ml in sulfuric ether. The reaction mixture is stirred for 2 hours at room temperature. After evaporation, dissolve The residue is discharged into 100 ml of H7hexane to precipitate solid 5-oxa-4-oxo-3 is sicarbonylaminobrendan (2.8 g). mp. (Recrystallization from benzene - n-hexane). IR spectrum ( Nujol, cm-): 3320, 1790, 1b90. 1380. Following the same procedure and using the product from example k as starting materials, the following compounds are synthesized: 5-Oxa-4-oxo-3-ethoxycarbonylaminoisotvistan with mp, 157 -159 ° C (recrystallization from isopropyl ether), IR spectrum (Nujol, cm-): 3330, 1730, 1710,. 6-Oksa-5-oxo-3-ethoxycarboiyl nogomobrendan, so pl. 90, 0 ° C (recrystallization from benzene-n-hexane). IR spectrum (KBG, cm: 3330, 1730-1700, 1520,. 6-Oxa-5-oxo-3-ethoxycarbonylamino-isootvistan, mp. 1182 (recrystallization from benzol - n-hexane), IR spectrum (Nujol, cm-): 3300, 1730-1700, 5-Oxa-1-oxo-9ndo-2-ethoxycarbonylaminoisotwistan, mp 157159 C (recrystallization from isopropyl ether), IR spectrum (Nuiol, 3300, 1780. 1700 Using the same procedure and using the starting materials from Example 3 as the starting materials, the following compounds are obtained: 5 Oxa-4-oxo-3-Cyanobrendan, mp 150-151 ° C (recrystallization from benzene - cyclohexane). IR spectrum KVG, cm): 2950, 2250, 1780, 10QO. 5-Ok a-; 4-oxo-3-cyano-isotvistan, mp 203-205 ° C (recrystallization from benzene). IR spectrum (KBG, cm-): 2950, 2250, 1790. 6-Ox-5-oxo- 3-carboxyhemobrendan with a melting point of 19.5-196.0 ° C (recrystallization from ethyl acetate). IR spectrum (Nuiol. Cm-) 2600, 1730, 1690, 1400, 1220. 5-Ox-5 -oxo-3-carboxybrendan, mp 15bg158 ° C, recrystallization from ethyl acetate. IR spectrum (Nujol, cm: 1720, 1200, 100. 5-0x-4-oxo-3-carboxy-isotvistan, mp, 5 ° C (recrystallization from ethyl acetate) IR spectrum (Nuiol) : 2650, 1780, 1710, 1300, 1070. EXAMPLE 6, To a solution of 15.0 g of exo-9-bromo-5-oxa-3-cyanobrendan and 100 mg of azobisisobutyronitrile in 300 ml of dry tetrahydrofuran are added , 5 g of tri-n-butyltin hydride in 100 ml of dry sulfuric ether. The reaction mixture is stirred for $ h at room temperature. Evaporation of the solvent gives an oily substance, which is passed through a chromatographic column with with benzene, elution of oily 5gox-3-cyanobrethane (10 g) is eluted. IR spectrum (film, cm): 2950, 2870, 2240, 1450, 1100. Following the same procedure, the following compounds are obtained: 5-Oxa-3- cyano-isotwistan with mt.p. IR spectrum (Nujol): 2250, 1480, 1440, 1340, 1080, 1040. 5-Oksa-3-oxymethylbrendan, oily substance, IR spectrum (film, cm) : ZbOO-ZYUO, 1450, 134o. Oily 5-oxa-3-hydroxymethylisotwistan, IR spectrum (film, 3600-3100, Y50, UtO. Oily 5-oxaendo-2-hydroxymethylbrendan. IR spectrum (film, 1440, 1360. Oily 5-oxaendo-2-hydroxymethyl isotwistan IR spectrum (film, CM 3500, 1100, 1080. Example. Ethanol solution 1.0 g 5-oxa-4-oxo-3 -ethoxycarbonylaminobrendan is added to calcium borohydride obtained from 1.46 g of dry calcium chloride and 0.671 g of sodium borohydride in dry ethanol, with stirring and at a temperature of 2-5 ° C. Stirring is continued for 5 hours. After removing excess borohydride calcium by the addition of a saturated solution of ammonium chloride concentrate the mixture to obtain a syrupy residue which is extracted with chloroform: The extracts are washed with a saturated solution of sodium chloride, dried and concentrated, an oily substance is obtained - endo-5-hydroxyendo-3-hydroxymethylexo-3-ethoxycarbonylamino-orbornan (0.9 g). IR spectrum (film, sM) 3400 ; 3350, 1680, 1540. Following the same procedure, the following compounds are obtained: Endo-5-hydroxy-endo-3-9 simethylsndo-2-ethoxycarbonylamino orbornane. IR spectrum (Nuiol, cm): 3430, 3350, 3250, 1700, 1520. Oily endo-5-hydroxyendo-3-hydroxymethylexo-3-ethoxycarbonylaminobicyclo 2,2,2-octane. IR spectrum (film, cm): ZbOO-ZYUO, 1700, 1520..Endo-5-hydroxyendo-3-hydroxymethylende-2-ethoxycarbonylaminobicyclo 2, 2.2 octene. IR spectrum (Muyol, cm 1): ZbOO, 3100, 1720, 1700, 1520. Endo-5-oksiendo-3- (f-oxyethyl) -exo-3-ethoxycarbonylaminonorbornan IR spectrum (Nuiol): 3330, 1700 , 1470, 1070. Endo-5-hydroxyendo-3- (pi-Oxy ethyl) -exo-3-ethoxycarbonylaminobicyclo 2,2,2 -octane. IR Spectrum. (Nujol, cm-): 3350, 1700, 1470. Oily endo-5-hydroxyendo-3-hydroxymethylende-2-cyanomethylnorbornane. IR spectrum (film,); 3350, 2250, 1460, 1430, 1140, 1120, 1060. Examples are p8, To a mixture of 10 ml of dry benzene, 5 ml of pyridine and 0.9 g of endo-5-hydroxyendo-3-hydroxymethylexo-3-ethoxycarbonylamino-orbornane, add 0.997 g para-toluensulfonyl chloride at 0-5 ° C for one hour, and the reaction mixture is stirred at room temperature for 8 hours. Then the reaction mass is discharged into a mixture of 100 ml of chloroform and 10% hydrochloric acid (50 ml). the organic layer is separated, washed, dried and concentrated under reduced pressure by chromatography on silica gel using chloroform. oily substance -5ox-3-ethoxycarbonylaminobrendan O, 34g IR spectrum (film, 3300, 2950. 1700, 1530, the following compounds are synthesized as an eluting solvent: An oily 5-oxaendo-2-ethoxycarbonylaminobrendan is synthesized in the same way. film, cm-1): 3300, 1700, 1540, 1200. 5-Occa-2-ethoxycarbonyl amino-itineology, mp 73.74.5 ° C. IR spectrum (film, cm-): 3300, 1700, 1550 , 1240. 5-Oxa-endo-2-ethoxycarbonylaminoisotwistan, mp 83-84 ° C. IR spectrum (film, cm-): 3320, 1720, 1540, 12bO Oily 6-oxa-3-ethoxycarbonylaminogram. -spectrum (film, C1): 3330, 2950, 2870, 177Q. Oil Nystoy-6-oxa-3-ethoxycarbonidaminogamoisotvistan IR spectrum (film, cm): 3350, 1700, 1540, 1260. 5-Oxaendo-2-M, M-diethylcarbamoylbrendan melting point 57-58.5 ° C. IR spectrum (KVg): 2850, 1640, 1485. Oily 5-oxa-3-Cyanobrendan. IR spectrum (film, cm-): 2950, 2870, 2240, 1450. -Oil 5 oxyando-2 -cyanomethylbrendan. IR spectrum (film, cm-):. 2950, 2250, 1060, 1000 .. Example9. A mixture of 40 ml of a 15% aqueous solution of potassium hydroxide and 1 g of 5-oxa-3-ethoxycarbonylaminobrendan is boiled under reflux for 7 hours. Then the product is extracted with chloroform. The extract was washed with brine, dried and concentrated. An oily 5-ox-3-aminobrendan (0.83 g) is obtained. IR spectrum (film, 3350, 3290, 2950, 1600, 1470. Following the described procedure and using as initial reagents

the products synthesized in Example 8 are oily 3x-endo-2-aminobrendan, infrared (film,): 3300, 3250, 3250, 1380, 1100.

EXAMPLE 10 With stirring and cooling, an ethanolic solution containing 1.8 g of endo-ZETOxycarbonylamino-endo-2-methoxycarbonyl-5-norbornene is added to calcium borohydride obtained from dry calcium chloride (3.2 g) and sodium borohydride (1, g) in dry ethyl alcohol. Stirring is continued for 5 hours at room temperature. After removing the excess calcium borohydride by adding a saturated solution of ammonium chloride, the mixture is concentrated to give a syrupy residue, which is extracted with chloroform. The extract is washed with a saturated solution of sodium chloride, dried and concentrated to give oily endo-3-ethoxycarbonylamino-2-hydroxymethyl-5-norbornene (1.5 g). IR spectrum (film, see): 3500, 2870, 1720, 1520.

Following the same procedure, the following compounds are obtained:

Oily exo-2-cyanoendo-2-hydroxymethyl-5-norbornene. IR spectrum (film, cm-), 2230, 1650, U80, 40, 1280..

Oily exo-2-cyanoendo-2-hydroxymethylbicyclo 2,2,2-oct-5-ene. IR spectrum (film, cm):, 2240, Y70, 1460, 1380.

Oily endo-3-ethoxycarbonylamine endo-2-hydroxymethylbicyclo-2, 2.2-oct-5 ene. IR (film, cm--): 3500, 2950, 1710, 1520.

Oily endo-3-N, N-diethylcarbamoyl-endo-2-hydroxymethyl-5-norbornene. IR spectrum (film, cm): 3400, 2950, 1630., 1270.

Oily endo-8-ethoxycarbonylamino-endo-9-hydroxymethyltricyclo 3,2,2, o} -non-6-ene. IR spectrum film, cm-: 3430, 3350, 1700, 1510.

Oily endo-3-hydroxymethyl exo-2- (2) -chloroethyl) -3-norbornene. IR spectrum (film, cm-): 3400, 2950., 1060.

Oily 5-oxa-3-oxymethylbrendan, which is identical in IR spectrum to the product synthesized in Example 6.

Example 11. While stirring at room temperature for 3 hours, a solution of 31b mg of 2,2-bis-oxymethyl-5-norbornene in 10 ml is added to a mixture of 637 mg of mercury acetate in 20 ml of water and 20 ml of tetrahydrofuran

tetrahydrofuran. To the reaction mixture was added 5 | 6 g of sodium hydroxide, and then 380 mg of sodium borohydride, and this operation was carried out with stirring during

2h As a result, mercury coagulates and precipitates. After decanting to remove mercury, the solution is concentrated and the residue is extracted with chloroform. The extract is washed

water, dried and evaporated to dryness, receive 300 ml of oily 5: oxa-3-hydroxymethylbrendan, which is identical in IR spectrum to the compound synthesized in Example 6.

Following this technique synthesize

the following compounds: oily 5-oxa-Zoxymethyl isotvistan, oily 5-oxa-endo-2-hydroxymethylbrendan, oily 5-oxa-endo-2-oxymethylisotvistane, oily 5 oxa-3 cyanobrendan, solid 5-oxo-3-oxo-3-oxo-3-oxo-3-cytobenstanane, oily 5 oxa-3 cyanobrendan, solid 5-oxa-3o-oxo-3-oxo-3-oxo-3-oxy-3 which, according to the IR spectrum, are identical to the compounds obtained in Example 6.

Oily 5 oxa-endo-2-ethoxycarbonylaminobrendan, solid 5-oxa-endo-2-ethocicarbonylaminoIsotvistan, solid 5-oxcaendo-N, M-diet, ilcarbamoylbrendan, which are identical to IR specimen of the compounds obtained from the same results obtained in the same sample obtained in the same way.

5-Oxa endo-2-ethoxycarbonylaminotetracyclo 4.4, Tgb, 0, 0 undecane with so pl. 100-102.5 ° C. IR spectrum

(Nujol, cm-: 3300, 1710, 1530, oily 5-oxaexo-2- (/ j-chloroethyl) -brendan. IR spectrum (film): 2950, 1470, 1360, 1280, 1120, oily 5-oxa-3-hydroxy-istvistan.

IR spectrum (film, cm-): 3300, 2950, 2870, 1420, 1100, 1050.

Claims (1)

EXAMPLE 12 A solution containing 4.3 g of 5 oxa-3-ethoxycarbonylaminobrendan in 20 ml of tetrahydrofuran is added to a mixture of lithium aluminum hydride (2.8 g) in 100 ml of tetrahydrofuran under reflux. 6 h; After decomposing excess lithium aluminum hydride by adding water, the reaction mixture is concentrated and a residue is obtained, which is extracted with chloroform. The extract is washed with a saturated solution of sodium chloride, dried and concentrated to give an oily Zuksa-3 -N-methylaminobrendan (2.8 g). IR spectrum (film, cm): 3380, 2950, 1450, 1080. Following the procedure described, the following compounds are obtained: Oily 5-oxa-3-M-methylamine isotwistan. IR spectrum (film,) 3300, 2950, U50, 1080. Oily 5-oxaendo-2-M-methyl aminoisotwistan, IR spectrum (film, CMI: 3200, 2930, 1470,. Oily 5-oKca-3 -N, N-dimethyl amyobrendan. IR spectrum (film, cm 2950, 2870, 1460. Oily 5-oxa-3-M, M-dimethyl aminoisotvistan. IR spectrum (film, cm-1): 2950, 2870, 1460 Example 13. To a solution of 850 m of 5-oxa-3-M-methylaminobrendan and 1.2 triethylamine in 20 ml of dry sulfuric ester was added 1.2 g of ethyl chloroformate in 50 m of anhydrous sulfuric ether with stirring at 0- 5 ° C overnight. The mixture is filtered, the filtrate is washed with hydrochloric acid ijacTBopoM ota and then with saturated sodium chloride solution, dried, and concentrated to give oily 5-OKca-3- (N-Me tyl-M-ethoxycarbonylamino) -brendan (900 mg). IR spectrum (film, cm): 3050 -2800, 1720-1680, 1440. Following the procedure of this example and using the products of example 12 as initial reagents, the following compounds are synthesized: Oily 5-oxa-3- (M-methyl-M-ethbxy) bonylamino) -isotwistan IR spectrum (film, cm-: 30-50-2 00 1720, 1440. Oily 5-oxa-3-benzyloxycarbonylaminomethylisotwistane. IR (film,): 3300, 2930, 1720, 1540, 1250, 700.. Example 14. To a solution of 1 g of 5-oxa-3-cyanobrendan in anhydrous tetrahydrofuran (10 ml) is added a mixture of 0.3 g of lithium aluminum hydride in 10 ml of anhydrous tetrahydrofuran with stirring at room temperature for 2 hours. After removing excess lithium aluminum hydride by adding water, the reaction mixture is concentrated, to obtain a residue, which is extracted with sulfuric ether. The extract is washed with a saturated solution of sodium chloride, dried and concentrated to give an oily 5-ox-3-aminomethylbrendan (0.8 g). Repeating the same procedure, the following compounds were obtained: Oily 5-oxa-3-aminomethyl isotwistan. IR spectrum (film, cm): 3400, 3300, 1030, 1010. Oily 5-oxaendo-2- (/ E-aminoethyl) -brendan. IR spectrum (film, 3400, 3320, 1040. Oily 5-oxa-3- (w-amino-ng-propyl) -isotwistan. IR spectrum (film, 3390, 3320, 1030, 1010. Oily 5- oxaexo-3- (i1-amino-n-propyl) brandan. IR spectrum (film, 3400, 3320, 1040. Example 15. To a solution of 1 g of 5-ox-3-aminomethylisotvistan in TO ml of anhydrous dichloromethane is added 9bO mg of trifluoroacetic anhydride with stirring at room temperature for 3 hours. Then it is poured into a mixture of 5% aqueous solution of sodium bicarbonate and chloroform and the organic layer is washed with water and dried. After removing the solvent, it is obtained 5-oxa 3-m-trifluoroacetylaminomethylisotwistan (0.9 g) with a melting point of 8U5-84 ° C. IR spectrum (Nujol, 3350-3050, 1700. Following the procedure described and using 1.52 g of 5-oxa -3-amino-isotwistan, 2 g of triethylamine and 0.86 g of acetyl chloride, give oily 5-oxa-3-M-acetylaminoisotwistan (800 mg). IR spectrum (Nuiol): 3400, 2960, 1660, 1560. Example 16 To a solution of 1.5 g of 5-oxa-3-aminomethylisotwistan in N, N-dimethylformamide (20 ml) were added 2.5 mg of benzyl chloride, followed by stirring for 5. h at. After cooling, the solution is poured into a mixture of water and sulfuric ether, the organic layer is separated, washed, dried and concentrated under reduced pressure, and oily 5-oxa-3-M-benzylminomethylisotvistan (1.2 g) is obtained. IR spectrum (film, cm-0: 3300, 2950, 1320,700, Example 17. A mixture of 1.9 g -Oxaendo-2- (p-chloroethyl) -brendan, 1.5b g of benzylamine 1.4 g of carbonate potassium and 19 ml of anhydrous M, M-diethylformamide. After cooling, the solution was poured into a mixture of water and sulfuric ether, and the organic sludge was separated, washed, dried, and concentrated under reduced pressure to give oily 5-oxa -2- / 3- (benz-zylamino) ethylbrendan IR spectrum (film, cm): 3300, 2950, 2850, 1350, 760. Example 18, To a solution of 300 mg of 5-oxa-3-benzyloxycarbonylamino-U methylisotwistan in 5 ml of anhydrous d and methyl sodium sulfoxide was added 123 mg of sodium hydrogenide b5 with stirring at IZO-IBO C for 1.5 hours. After cooling, 158 solution of 518 mg of ethyl iodide in 5 ml of anhydrous dimethylformamide was added to the mixture 15 and stirred at 9 ° C in for 10 hours, then poured into a mixture of benzene and water and extracted with benzene 20. The extract is washed, dried and concentrated, an oily product is obtained. The subsequent chromatographic purification on silica gel using as solvent elues of chloroform solids gives oily 5-oxa-3- (M-ethyl-M-benzyloxycarbonyl) aminomethylisotvistan (450 mg). IR spectrum. (Film, cm): 2930 , 2860,. J1700, U60, 1250, 700.30 where the claims of the invention are the method of producing tricyclic compounds of general formula I AiTJRiBj where A is a simple bond or C-C-alkylene in position 2 or 3 A2 is alkylene; AJ — simple bond or C —C-alkylene; X is oxygen or sulfur, one of R and R is hydrogen or R and R2 independently of each other are C-C ELKIL, C-CD-aralkyl, C2 C5-alkoxycarbonyl, C2 C-alkanoyl, C-Cj-raloidalkanoyl or benzyloxycarbonyl, wherein, a compound of the general formula: where, under or where, or 35, where, or 40 (50, where, under where, and AiTfHBj, X and R have the indicated meanings, they interact with R, In addition to hydrogen, Z is a halogen, alkanoyloxy or haloalkanoyloxy, a compound of the general formula fv AilfHKg A ,, -Aj, X and R2 have the indicated values 1, they interact Twine with a compound of the general formula RZ Z has the indicated values, R4 takes the values of R except hydrogen, the compound of the general formula i / i CHg-S, X and Z have the indicated values, reacts with the amine of the formula VII R and R2 has the indicated values solvent at tempera1798819218 round from to the boiling point 1. Weigand-Hilgetag. Methods solvent., experiment in organic chemistry. Sources of information, missions. M., Himi, 1968, p. k taken into account in the examination,