Tricyclic derivatives of pyrrole, pharmaceutical drug

 

(57) Abstract:

The invention relates to tricyclic derivatives of pyrrole General formula (I), where R1-R4denote hydrogen, halogen, lower alkyl, phenyl, cycloalkyl or lower alkoxy, a R2indicates additional lower alkoxycarbonyl, acyloxy or mesilate; R5denotes lower alkyl; R6, R7represent hydrogen or lower alkyl; X represents-CH2CH(C6H5), -CH= C(C6H5)-, -YCH2-, -CH=CH - (CR11R12)n; R11and R12denote hydrogen, phenyl, lower alkyl; h denotes 1-3 and Y denotes O or S, and pharmaceutically acceptable acid additive salts. Pharmaceutical drug has the ability of binding to serotonin receptors. These compounds are effective primarily at combating or prevention of disorders of the Central nervous system, as depression, bipolar disorders, fear, sleep disturbances and disorders in the sexual sphere, psychosis, schizophrenia, migraine headaches and other painful conditions associated with headaches and pain of another type, disorders related to personal experiences or obsessive ideas, social FOB is you want to make, memory impairment, age-related disorders of relationships with others, painful passion, obesity, bulimia, etc.; disorders of the nervous system caused by trauma, bleeding in the brain, neuro-degenerative diseases, and so on ; disturbances in the cardiovascular system, such as high blood pressure, thrombosis, stroke, and so on; and gastrointestinal disorders, as dysfunction of the motility of the gastrointestinal tract. 2 C. and 10 C.p. f-crystals, 6 PL.

The invention relates to tricyclic derivatives of pyrrole, in particular it relates to the derivatives of pyrrole General formula

< / BR>
where R1-R4denote hydrogen, halogen, lower alkyl, phenyl, cycloalkyl or lower alkoxy, a R2means are also lower alkoxycarbonyl, acyloxy or mesilate;

R5denotes lower alkyl;

R6and R7represent hydrogen or lower alkyl;

X denotes-CH2CH(C6H5)-, -CH= C(C6H5)-, -YCH2-, -CH=CH-, or -(CR11R12)n;

R11and R12denote hydrogen, phenyl, lower alkyl;

n denotes 1 to 3; and

Y denotes O or S,

and their pharmaceutically acceptable acid-additive and properties.

The object of the present invention are compounds of General formula I and their pharmaceutically acceptable salts, as such, and as pharmaceutical active substances, the formation of compounds and salts of General formula I, hereinafter, drugs containing these compounds and salts of formula I, and obtain these medicines, as well as the use of compounds of General formula I and their pharmaceutically acceptable salts for the treatment and, accordingly, prevent disease and improve health, especially for the treatment or prevention of disorders of the Central nervous system, as depression, bipolar disorders, fear, sleep disturbances and disorders in the sexual sphere, psychosis, schizophrenia, migraine headaches and other painful conditions associated with headaches and pain of another type, disorders related to personal experiences or obsessive ideas, social phobia or panic attacks, mental organic disorders, mental disorders in childhood, aggressiveness, memory impairment, age-related disorders of relationships with others, painful passion, obesity, bulimia, etc.; disorders of the nervous system caused by trauma, hemorrhage in m is a t, thrombosis, stroke, and so on; gastro-intestinal disorders, as dysfunction of the motility of the gastrointestinal tract, and for the manufacture of the drugs.

Compounds of General formula

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where R1-R7have the above values, a R8denotes translated into the amino radical or a hydroxyl group,

represent important intermediate products to obtain pharmaceutically valuable compounds of General formula I.

The above definition of "lower" denotes a radical with the number of carbon atoms and a maximum of 7, preferably up to 4. Alkyl denotes a linear or branched saturated hydrocarbon radicals, such as methyl, ethyl, propyl, isopropyl or tert.-butyl. Alkoxy denotes linked through the oxygen atom of the alkyl group. The halogen may denote Cl, Br, F or J. Pharmaceutically acceptable acid additive salts include salts of inorganic and organic acids as hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanol the ptx2">

If R5denotes methyl, are particularly preferred are compounds where R1, R3and R4represent hydrogen, and R2denotes halogen, lower alkyl or methoxy.

Some specified within the scope of this invention as particularly preferred representatives of the class of compounds according to formula I are the following:

(S)-2-(4,4,7-trimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1 - methylethylamine,

(S)-2-(7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b]pyrrol - 1-yl)-1-methylethylamine,

(S)-2-(7-ethyl-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrol - 1-yl)-1-methylethylamine,

(S)-2-(7-methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine,

(S)-2-(7-bromo-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine,

(S)-2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine,

(S)-2-(7-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine,

(S)-2-(8-methoxy-1H-Benz[g]indol-1-yl)-1-methylethylamine.

Compounds of General formula I and their pharmaceutically acceptable salts can be obtained according to the invention in the following way:

a) compound of General formula

< / BR>
where R1-R7have the above values, a R81denotes translated into the amino radical,

revocat in pharmaceutically acceptable salt.

Compounds of General formula IIa, where R81denotes translated into the amino group of residue, preferably sidegroup, acetylamino or any other protected amino group can be obtained, as described below, using known methods. If the radical R81is sidegroup, the compounds of formula I are obtained by recovery. This recovery can be done using complex hydrides, such as, for example, socialogical, or by catalytic hydrogenation using a metal catalyst, such as platinum or palladium. When in use as a reducing agent socialogical, the solvent most suitable simple anhydrous ether or tetrahydrofuran. The process is expediently done in the following way. After the addition dropwise of compounds of formula IIa, where R81denotes sidegroup, in a solution containing anhydrous solvent and the hydride, the reaction mixture is refluxed, and then hydrolyzing an aqueous solution of simple ether or THF and the precipitate of aluminium hydroxide and lithium is boiled with an aqueous solution of simple ether or THF.

Catalytic hydrogenation of the E. As solvents are particularly suitable for this purpose are water, alcohols, ethyl acetate, dioxane or mixtures of these solvents. Hydrogenation is advisable to carry out in an atmosphere of hydrogen in the autoclave or in the apparatus for shaking. If R81denotes acetylamino or any other protected amino group, such as, for example, triftormetilfullerenov, the translation into the corresponding aminosidine carried out by hydrolysis.

Hydrolysis to the corresponding amino compounds of General formula I is carried out by well-known methods. Suitable for this purpose are metal hydroxide, e.g. sodium hydroxide or potassium, which in the presence of water and miscible with water and organic solvent as ethylene glycol, etc., hydrolyzing to compounds of formula I.

Translation of the compounds of formula I in their corresponding acid salt additive is carried out on the last stage, i.e. after hydrogenation or hydrolysis without intermediate allocation of compounds of formula I.

Because of their stabilizing properties particularly suitable for pharmaceutical applications salts of fumaric acid. However, all other above-mentioned acid form of the pharmacologically reception is especially suitable alcohol-ether mixture. The intermediate products of the formula II used for the synthesis of compounds of General formula I, depicted in figure 1 (see end of description). In this case, all the substituents R1-R4have the meanings indicated in formula I. R51, R61and R71denote methyl. Me denotes methyl, and Ac is acetyl. X has the meaning indicated in formula I, in addition to the-CH=CH-. Obtaining the corresponding compounds where X is-CH=CH-, presented in figure 2 (see the end of the description).

Obtaining compounds of formula IIa2, based on compound III, preferably carried out as follows:

The compound of formula III is heated under reflux with 3-butene-2-I, 2,2-dimethoxypropane and catalytic amounts of p-toluenesulfonic acid in anhydrous toluene. In another embodiment, the solvent is 2,2-dimethoxypropane without the use of toluene. In this case, the reaction mixture is heated under reflux in filled with molecular sieve the water separator. Then, thus obtained the compounds of formula IV are transferred to the appropriate xoetrope connection. To this end, the compound IV is dissolved in an anhydrous solvent, such as dichloromethane and methanol, and at a temperature of CA is about proletarianisation. It is advisable to apply in this case N-acetylethylenediamine, and the solvent is toluene or acetic acid. After completion of the exchange reaction and purification of acetyl group may, as indicated above, be chipped off and the compound of formula IIa2 to transfer to the compound of formula I.

Proceeding from compounds of formula V, preferably by cyclization using 1-amino-2-propanol in anhydrous toluene using catalytic amounts of p-toluenesulfonic acid by heating in the separator receive a hydroxyl compound of the formula IIb12. Then the hydroxyl group by well-known methods can be converted to a leaving group, for example, by treatment with a chloride sulfonic acids, preferably by methanesulfonamido, the sulfonate. As a result of processing azide, preferably sodium azide, in a polar solvent, such as DMF, the compounds of formula IIb12 can be translated into the appropriate etidocaine formula IIa12, which, as mentioned above, by restoring azido group can be converted to compounds of formula I.

The compounds of formula V can be obtained according to scheme 1 is also another way.

The compound of formula III is preferably heated with N,N-dimetional VII is treated with DMP (1,3 - dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone), dissolved in anhydrous THF, cooled to about -75oC and then treated with n-butyllithium in hexane and bromochlorodimethylhydantoin.

Then, the resulting compound of formula VIII using phosphate buffer and chloride dihydrate, copper (II) in THF was transferred to the compound of formula V.

According to scheme 1 can be obtained the compounds of formula IIb11. These compounds can then be, as described above, transferred to the connection 10 of the formula I. it is Advisable to work as follows: the Compound of formula III dissolved in anhydrous THF, is treated with Diisopropylamine and n-butyllithium, followed by treatment with chloroacetone, respectively, 3-chloro-2-butanone. The compounds VI are heated in the water separator in anhydrous toluene with catalytic amounts of p - toluenesulfonic acid. Then treated with 1-amino-2-propanol to obtain the compounds of formula IIb11.

Figure 2 illustrates the formation of compounds of formula IIa22, where R1-R7have the meanings given above and X represents-CH=CH-, R10can be a methyl or triptorelin group.

It is advisable to work as follows: the Compound of formula Ia is subjected is storytale, preferably methanol. After removal of solvent the residue is dissolved in dioxane and treated with BCH (2,3-dichloro-5,6-dicyan-1,4-benzoquinone). Then the protective group as described above, to split from the amino group.

As noted above, the compounds of formula I and their pharmaceutically acceptable salts have valuable pharmacological properties. They can bind to serotonin receptors and therefore suitable for the treatment or prevention of diseases or functional disorders of the above-mentioned type, respectively, for the manufacture of the drugs.

Binding offer according to the invention compounds of formula I with serotonin receptors was determined using standard in vitro methods. The drugs were tested in the following tests.

The method I

(a) binding of 5HT1A-receptor according to test binding3H-8-OH-DPAT by the method of S. J. Peroutka, Biol. Psychiatry 20, 971-979 (1985).

b) For the binding of 5HT2C-receptor according to test binding3H - mesulergine method A. Pazos et al., Europ. J. Pharmacol. 106, 539 - 546, respectively D. Hoyer, Receptor Research 8, 59-81 (1988).

C) To associate 5HT2A-receptor according to test binding3H - keenser pitamah substances, i.e. a concentrations were determined in nm, which was superseded 50% associated with the receptor ligand.

Determined by the activity of some compounds according to the invention and the comparative activity of some compounds are presented in table. 1, where the following notation:

3 = (S)-2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine;

4 = (S)-2-(7-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine;

5 = (S)-2-(8-methoxy-4,5-dihydro-1H-benzo[g]indol-1-yl)- 1-methylethylamine;

7 = (S)-2-(8-methoxy-1H-Benz[g]indol-1-yl-1-methylethylamine;

21 = (RS)-2-(7-chloro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1 - methylethylamine;

22 = (RS)-2-(7-methoxy-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-1 - methylethylamine;

23 = 2-(7-methoxy-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)- ethylamine;

28 = (R)-2-(7-methoxy-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)- 1-methylethylamine;

30 = (R)-2-(8-methoxy-4,5-dihydro-1H-benzo[g]indol-1-yl)-1 - methylethylamine;

31 = (R)-2-(8-methoxy-1H-Benz[g]indol-1-yl)-1-methylethylamine;

32 = 2-(8-methoxy-1H-Benz[g]indol-1-yl)-ethylamine;

34 = (RS)-1-(1,4-dihydro[1]benzopyrano[4,3-b]pyrrol-1-yl)- 1-methylethylamine;

53 = (RS)-2-(6-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)-1-10 methylethylamine;

54 = (RS)-1-(8-methoxy-1,4-dihydro[1]benzopyrano[4,3-b] pyrrol-1-yl)-ihydro-1H-benzo[g]indol-1-yl)-ethylamine;

64 = (RS)-1-(1,4-dihydro [1] benzothiophene [4,3-b] pyrrol-1 - yl)-1-methylethylamine;

67 = (RS)-2-(8-methoxy-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)- 1-methylethylamine;

69 = (2RS,4RS)-2-(4-phenyl-1,4-dihydroindeno [1,2-b] pyrrol-1 - yl)-1-methylethylamine.

Method II

a) To identify affinity connection with 5HT1Areceptor conducted experiments on the displacement of [3H] 5-HT (1 nm) as radioligand on reconstituted 5HT1Athe receptors of the man, ekspressirovannoj in cells C mice. Used membranes obtained from cells 2105and various concentrations of the appropriate test compound.

b) For the binding of 5HT2C-receptor according to test binding of [3H]-30 5-HT by the method of S. J. Peroutka et al., Brain Research 584. 191-196 (1992).

C) To associate 5HT2A- receptor according to test binding of [3H] - DOB according to the method of T. Branchek et al. , Molecular Pharmacology 38, 604 - 609 (1990).

Below are the values of pki(pki=log10Ki) of the tested substances. The value of ki is decrypted according to the following formula:

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where the values of the IC50correspond to the concentrations of the tested compounds in nm, in which displaced 50% associated with the receptor ligand. [L] is the ligand concentration, and meant the th of some compounds according to the invention are presented in table. 2, where the following notation:

1 = fumarate (S)-2-(4,4,7-trimethyl-1,4-dihydroindeno[1,2-b]pyrrol - 1-yl)-1-methylethylamine (1:1):

2 = fumarate (8)-2-(7-methoxy-4,4-dimethyl - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:1);

8 = (S)-2-(7-ethyl-4,4-dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)-1-methylethylamine (1:1);

9 = fumarate (S)-2-(7-fluoro-4,4-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:1);

12 = fumarate (S)-2-(7-methoxy-4,4-diethyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5);

14 = fumarate (S)-2-(7-phenyl-1.4-dihydroindeno[1,2-b]pyrrol-1 - yl)-1-methylethylamine (1:0,5);

17 = fumarate (S)-2-(7-ethyl-1,4-dihydroindeno [1,2-b]pyrrol-1 - yl)-1-methylethylamine (1:0,5);

25 = fumarate (S)-2-(6,7-debtor-1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)-1-methylethylamine (1:0,5);

26 = fumarate (S)-2-(6-chloro-7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5);

37 = fumarate (RS)-2-(5-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)-1-methylethylamine (1:0,5);

44 = fumarate (S)-1-methyl-2-(7'-methyl-1',4'-dihydrospiro [cyclopentane-1,4'-indeno[1,2-b]pyrrole]-1-yl)-ethylamine (1:1);

50 = fumarate (RS)-2-(5-methyl-1,4-dihydroindeno[1,2-b]pyrrol - 1-yl)-1-methylethylamine (1:0,5).

The erection of the penis (in rats)

During the experiments it was found that the erection floor is">

Within 45 min after administration of test animals test substance was determined by the number of erections of the penis. ED50indicates the dose which causes 50% of such erections (table 3).

The compounds of formula I and pharmaceutically acceptable additive, acid salts of compounds of formula I can be used as medicines, for example, in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, for example in the form of tablets, lacquered tablets, coated tablets, megkozeliteni and terdoslavich capsules, solutions, emulsions or suspensions. The introduction, however, can also be carried out rectally, for example, suppository, parenteral, for example, in the form of solutions for injection, or through the nose.

For the manufacture of pharmaceutical preparations of the compounds of formula I and pharmaceutically acceptable additive, acid salts of compounds of formula I can be added inert pharmaceutical respect, inorganic or organic fillers. As such for tablets, lacquered tablets, coated tablets and terdoslavich capsules are used, for example, lactose, corn starch or its derivatives, talc, stearic acid sludge is Usc, fats, semi-solid and liquid polyols etc., However, depending on certain properties of the active substance for megkozeliteni capsules in General, you may not have any fillers. For the manufacture of solutions and syrups as fillers suitable, for example, water, polyols, glycerine, vegetable oil, etc. as excipients for suppositories are suitable, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols, etc.

The pharmaceutical preparations may contain, in addition, also preservatives, substances that promote solubility, stabilizers, humectants, emulsifiers, chemicals, improves taste, colouring agents, flavouring agents, salts for modifying the osmotic pressure, buffers, shell, or antioxidants. They can also contain other therapeutically valuable substances.

Drugs, containing a compound of formula I or its pharmaceutically acceptable additive salt of the acid and a therapeutically inert excipient are also an object of the present invention and the method of their manufacture, wherein the one or more compounds of the formula I and/or pharmaceutically bramlet in herbal form.

According to the invention compounds of General formula I and their pharmaceutically acceptable additive, acid salts can be used for the treatment or prevention of disorders of the Central nervous system, as depression, bipolar disorders, fear, sleep disturbances and disorders in the sexual sphere, psychosis, schizophrenia, migraine headaches and other painful conditions associated with headaches and pain of another type, disorders related to personal experiences or obsessive ideas, social phobia or panic attacks, mental organic disorders, mental disorders in childhood, aggressiveness, memory impairment, age-related violations of relationships with others, painful passion, obesity, bulimia, etc. ; disorders of the nervous system caused by trauma, bleeding in the brain, neuro-degenerative diseases, and so on; disturbances in the cardiovascular system, such as high blood pressure, thrombosis, stroke, and so on; gastro-intestinal disorders, as dysfunction of the motility of the gastrointestinal tract, and for the manufacture of the drugs. The dosage can vary within wide limits, taking into account, of course, in each otdelnogo 500 mg (daily dose) compounds of General formula I or the corresponding number of its pharmaceutically acceptable salt additive acid, moreover, the upper bound, if appropriate, may also be exceeded.

Below the present invention is illustrated in more detail by way of examples, which in no way limit its scope. All temperatures are in degrees Celsius.

Example 1

a) a Solution of 18.9 g (108 mmol) 3,3,6-trimethyl-1-indanone of 22.4 ml of 0.26 mole) of 3-butene-2-ol and 300 mg of p-toluenesulfonic acid in 200 ml of 2,2 - dimethoxypropane for 64 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 6:1). Along with 4.5 g of educt was obtained 12.7 g (51%) of (RS)-2-(2-butene-1-yl)-3,3,6-trimethyl-1-indanone as a yellow oil.

b) cooled to -70oa solution of 12.7 g (55.6 mmol) of (RS)-2-(2-butene-1-yl)-3,3,6-trimethyl-1-indanone in 200 ml of anhydrous dichloromethane and 40 ml of anhydrous methanol under stirring for 60 min was passed a stream of ozone (2.5 g ozone/hour). Then in the solution for 5 min passed and oxygen for 10 min argon. After the addition 6,12 ml (of 83.4 mmole) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was wplaty was stirred for 2.5 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized additives with a spatula of sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was twice extracted with dichloromethane, respectively, portions of 150 ml the combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result was obtained 11.3 g (94%) of (RS)-2-(2-oxoethyl)-3,3,6 - trimethyl-1-indanone in the form of oil, lightly colored in yellow.

C) a Solution of 2.16 g (10 mmol) of (RS)-2-(2-oxoethyl)-3,3,6-trimethyl-1-indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then boiled for 45 min, and the volume of solvent was reduced to 20 ml of the Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:2). The result was obtained 1.5 g (59%) of (R)-1-(4,4,7-trimethyl-1,4-dihydro-indeno[1,2-a 5-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0 a solution of 1.5 g (by 5.87 mmol) of (R)-1-(4,4,7 - trimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol 3.27 ml (23.5 mmole) of triethylamine in 50 ml of mesylate for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml dichloromethane, washed twice with a saturated solution of sodium bicarbonate portions 70 ml) and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained solid green color was dissolved in 50 ml of anhydrous dimethylformamide, treated 0,76 g (11.7 mmol) of sodium azide and the reaction mixture was heated with stirring for 15 h 60o. After cooling the solution was poured into 100 ml of water and was extracted twice with ethyl acetate respectively in portions of 100 ml the combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in vacuum. The resulting brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). The result obtained 1.13 g (68%) of (S)-1-(2-azithromy)-4,4,7-trimethyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of a reddish oil.

d) 1.1 g (to 3.92 mmole) of (S)-1-(2-azithromy)-4,4,7-trimethyl-1,4 - dihydroindeno [1,2-b] pyrrole, retroville from catalyst washed with ethanol and the solution is kept in vacuum. The obtained colorless oil was dissolved in 80 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 455 mg (to 3.92 mmole)of fumaric acid in 15 ml of methanol. Then was stirred for 24 h at room temperature, then was filtered white crystals. As a result received 805 mg (77%) fumarata (S)-2-(4,4,7-trimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:1) with So pl. 196o.

Example 2

a) a Solution of 12.1 g (63.7 mmole) 6-methoxy-3,3-dimethyl-1-indanone, 11,1 ml of 0.13 mole) of 3-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2-dimethoxypropane boiled for 67 h under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). Along with with 4.64 g of educt received 5,86 g (38%) of (RS)-2-(2-butene-1-yl)-6 - methoxy-3,3-dimethyl-1-indanone as a yellow oil.

b) cooled to -70othe solution 5,86 g (24 mmole) of (RS)-2-(2 - butene-1-yl)-6-methoxy-3,3-dimethyl-1-indanone in 100 ml of anhydrous dichloromethane and 20 ml of anhydrous methanol under stirring missed during Le supplements of 2.64 ml (36 mmol) of dimethyl sulfide was stirred for 4 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 60 ml of dichloromethane and, after addition of 10 ml water and 10 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized additives with a spatula of sodium bicarbonate. After this was added 50 ml of water, the phases were separated and the aqueous phase was extracted twice with dichloromethane, respectively, portions of 150 ml the combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 4.94 g (89%) of (RS) -2- (2-oxoethyl)-6-methoxy-3,3-dimethyl-1-indanone in the form of a yellowish oil.

C) a Solution of 4.94 g (21.3 mmole) of (RS)-2- (2-oxoethyl)-6-methoxy-3,3-dimethyl-1-indanone and 220 mg of p-toluenesulfonic acid in 200 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution to 6.39 g (85.2 mmol) of (R)-1-amino-2-propanol in 40 ml of anhydrous toluene. Then boiled for 45 min, and the volume of solvent was reduced to 40 ml of the Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been of 3.42 g (60%) of (R)-1-(7-methoxy-4,4-dimethyl-1,4 - dihydro which g (12.7 mmol) of (R)-1-(7-methoxy-4,4-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)- propan-2-ol and 7.3 ml (50.8 mmol) of triethylamine in 70 ml of dichloromethane under stirring was added dropwise a 2.0 ml (25.4 mmol) methanesulfonanilide and stirred for 1.5 h at this temperature. Then the reaction mixture was diluted with 170 ml of dichloromethane, washed twice with a saturated solution of sodium bicarbonate, respectively portions 90 ml) and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 90 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 70 ml of anhydrous dimethylformamide, and treated with 1.35 g (20.4 mmol) of sodium azide and the reaction mixture is heated under stirring for 20 h 60o. After cooling the solution was poured into 100 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, then dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). The result has been 1,89 g (50%) of (S)-1-(2-azithromy)-7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b]pyrrole as a yellow oil.

d) 1,89 g (6.38 mmol) of (S)-1-(2-azithromy)-7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b]portroyal from catalyst washed with ethanol and the solvent was removed in vacuum.

The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 740 mg (6.38 mmol) of fumaric acid in 15 ml of methanol. Within 15 h and was stirred at room temperature and then was filtered white crystals. The result has been a 1.46 g (60%) fumarata (S)-2-(7-methoxy-4,4 - dimethyl - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:1) with So pl. 181o.

Example 3

a) a Solution of 9.3 g (57,3 mmol) 6-methoxy-1-indanone, and 11.8 ml (about 0.14 mole) of 3-butene-2-ol and 100 mg of p-toluenesulfonic acid in 100 ml of 2,2-dimethoxypropane for 64 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). The result has been to 9.2 g (74%) of (RS) -2-(2-butene-1-yl)-6-methoxy-1-indanone as a yellow oil.

b) cooled to -70oa solution of 15.2 g (70.3 mmol) of (RS)-2-(2-butene-1-yl)-6-methoxy-1-indanone in 250 ml of anhydrous dichloromethane and 50 ml of anhydrous methanol under stirring missed during 80 min stream of ozone (3 g moles) of dimethyl sulfide was stirred for 15 h at room temperature. Then the reaction mixture was evaporated in vacuo, the residue was treated with 250 ml of dichloromethane and, after addition of 25 ml water and 25 ml triperoxonane acid was stirred for 3 h at room temperature. Then the reaction mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then was added 100 ml of water, the phases were separated and the aqueous phase was twice extracted with dichloromethane, respectively, portions of 150 ml the combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from diethyl ether/hexane. The result obtained 12 g (83%) of (RS)-2- (2-oxoethyl)-6-methoxy-1-indanone as a yellowish solid with So pl. 59o.

C) a Solution of 2 g (9.8 mmol) of (RS)-2-(2-oxoethyl)-6-methoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution to 2.94 g (39.2 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then boiled for 30 min, and the volume of solvent was reduced to 20 ml of the Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate the Dogo substances So pl. 75o.

g) cooled to 0oa solution of 1.5 g (6.2 mmol) of (R)-1-(7 - methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.45 ml (approximately 24.6 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 0.96 ml (12.3 mmol) of methanesulfonamide and stirred for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice with a saturated solution of sodium bicarbonate, respectively portions 70 ml) and the combined aqueous phases were extracted once with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 60 ml of anhydrous dimethylformamide, treated of 0.77 g (11.8 mmol) of sodium azide and the reaction mixture was heated with stirring for 15 h 60o. After cooling the solution was poured into 140 ml of water and was extracted twice with diethyl ether, respectively portions 140 ml the combined organic phases are washed once with 100 ml water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained CDF is (60%) of (S)-1-(2-azithromy)-7-methoxy-1,4-dihydroindeno[1,2-b] pyrrole as a colorless oil.

d) 1 g (3.7 mmole) of (S)-1-(2-azithromy)-7-methoxy-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol was first made using 100 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent was removed in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 240 mg (2,07 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. As a result received 870 mg (77%) fumarata (S)-2-(7-methoxy-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) So pl. 206oC.

Example 4

a) a Solution of 20.2 g (0.12 moles) of 6-chloro-1-indanone, 25 ml of 0.29 mole) of 3-butene-2-ol and 200 mg of p-toluenesulfonic acid in 25 ml of 2,2 - dimethoxypropane and 200 ml of anhydrous toluene was heated for 16 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result obtained 10.3 g (39%) of (RS)-2-(2-butene-1-yl)-6-chloro-1 - indanone as a yellow oil.

b) cooled to -70oa solution of 10.3 g (46.7 mmol) of (RS)-2-(2-bScale for 45 min stream of ozone (3 g ozone/hour). Then the solution was passed for 5 min and oxygen for 10 min argon. After the addition 5,13 ml (70 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 60 ml of dichloromethane and, after addition of 15 ml water and 15 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 150 ml of water and neutralized with stirring, adding with a spatula sodium bicarbonate. After this was added 100 ml of water, the phases were separated and the aqueous phase was extracted twice with dichloromethane, respectively, portions of 150 ml the combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from ethyl acetate/hexane. The result has been 8,29 g (85%) of (RS)-2-(2-oxoethyl)-6-chloro-1-indanone as a white solid with So pl. 80oC.

C) a Solution of 2.5 g (12.0 mmol) of (RS)-2-(2-oxoethyl)-6-chloro-1 - indanone and 100 mg p-toluenesulfonic acid in 120 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.6 g (47.9 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then boiled for 30 is Oh chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been 2,42 g (81%) of (R)-1-(7-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2 - ol as a brown oil, which was directly used for the subsequent reaction.

g) cooled to 0othe solution to 2.42 g (9.8 mmol) of (R)-1-(7-chloro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 5,48 ml (39.1 mmol) of triethylamine in 70 ml of dichloromethane under stirring was added dropwise 1,53 ml (19,54 mmol) methanesulfonanilide and stirred for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, and treated with 1.27 g (19,54 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 100 ml of water and was extracted twice with diethyl ether, respectively portions 140 ml and once with 70 ml of orida sodium, was dried over magnesium sulfate and the solution was concentrated in vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 1.5 g (56%) of (S)-1-(2 - azithromy)-7-chloro-1,4 - dihydroindeno[1,2-b] pyrrole in the form of butter.

d) 1.5 g (5.5 mmol) of (S)-1-(2-azithromy)-7-chloro-1,4-dihydro-indeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made by using 150 mg of platinum oxide for 14 hours and Then was filtered from the catalyst, washed with ethanol and the solvent was removed in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 306 (2,64 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 3 h at room temperature, then was filtered white crystals. The result obtained 1.12 g (67%) fumarata (S)-2-(7-chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) So pl. 197o.

Example 5

a) a Solution of 2 g (9.2 mmol) of (RS)-2-(2-oxoethyl)-7-methoxy-1 - tetralone and 100 mg p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2,78 g (37 mmol) of (R)-1-amino-2-Pro Jr. The cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been 2.25 g (94%) of (R)-1-(4,5-dihydro-8-metoki-1H-benzo[g] indol-1 - yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

b) cooled to 0oa solution of 2.25 g (9 mmol) of (R)-1-(4,5 - dihydro-8-methoxy-1H-Benz[g] indol-1-yl)-propan-2-yl and 5 ml (36 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise to 1.4 ml (18 mmol) of methanesulfonamide and stirred for 1.5 h at this temperature. Then the reaction mixture was diluted with 300 ml diethyl ether, washed twice with a saturated solution of sodium bicarbonate, respectively, portions of 100 ml and the combined aqueous phases once was extracted with 100 ml diethyl ether. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated at 1.17 g (18 mmol) of sodium azide and with stirring, the reaction mixture was heated for 15 h 60o. After cooling the solution was poured into 140 ml of water is washed once respectively 100 ml of water and 100 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and the solution was concentrated in vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 1.78 g (71%) of (S)-1-(2-azithromy)-4,5-dihydro-8-methoxy-1H-Benz[g] indole as a colorless oil.

in) 2,78 g (9.8 mmol) of (S)-1-(2-azithromy)-4,5-dihydro-8-methoxy-1H-Benz [g] indole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 280 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent was removed in vacuum. 700 mg (2.7 mmole) obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 317 mg (2.7 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 2 h at room temperature, then was filtered white crystals. As a result received 820 mg (81%) fumarata (S)-2-(4,5-dihydro - 8-methoxy-1H-benzo[g]indol-1-yl)-1-methylethylamine (1:1) with so pl. 193o.

Example 6

a) a Solution of 19.7 g (0,13 mol) of 6-fluoro-1-indanone of 27.0 ml (0,31 mole) of 3-butene-2-ol and 200 mg of p-toluenesulfonic acid in 200 ml of 2,2 - dimethoxypropane for 67 h boiled under reflux in the filled molecular the your column chromatography on silica gel (hexane/diethyl ether 4:1). The result has been to 18.9 g (71%) of (RS)-2-(2-butene-1-yl)-6-fluoro-1-indanone as a yellow oil.

b) cooled to -70oa solution of 18.9 g (92.5 mmol) of (RS)-2-(2 - butene-1-yl)-6-fluoro-1-indanone in 300 ml of anhydrous dichloromethane and 60 ml of anhydrous methanol under stirring missed during 100 min stream of ozone (3 g ozone/hour). Then in the solution for 5 min passed and oxygen for 10 min argon. After the addition of 10.2 ml (140 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 300 ml of dichloromethane and, after addition of 43 ml of water and 43 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 200 ml of water and with stirring, neutralized by adding at the tip of a spatula sodium bicarbonate. After this was added 100 ml of water, the phases were separated and the aqueous phase was extracted twice respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from diethyl ether/hexane. The result has been 16.5 g (92%) of (RS)-2-(2 - oxoethyl)-6-fluoro-1-indanone in the form of a white solid with so pl. 62

g) cooled to 0oa solution of 1.73 g (7.5 mmol) of (R)-1-(7-fluoro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 4.2 ml (29.9 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise at 1.17 ml (15.0 mmol) of methanesulfonamide and stirred for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml of diethyl ether, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The oil obtained reaction mixture with stirring, was heated for 15 h 50o. After cooling the solution was poured into 110 ml of water and was extracted twice respectively portions 110 ml of diethyl ether and once with 60 ml of ethyl acetate. The combined organic phases are washed once respectively 80 ml of water and 80 ml of saturated solution of sodium chloride, dried over magnesium sulfate and the solution was concentrated in vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). As a result received 750 mg (39%) of (S)-1-(2-azithromy)-7-fluoro-1,4-dihydroindeno[1,2 - b] pyrrole as a colorless oil.

d) 750 mg (2.9 mmole) of (S)-1-(2-azithromy)-7-fluoro-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 75 mg of platinum oxide for 15 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 370 mg (1,46 mmole) of fumaric acid in 20 ml of ethanol. Then was stirred for 3 h at room temperature, then was filtered white crystals. As a result received 460 mg (54%) fumarata (S)-2-(7-fluoro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-th is-1H-benzo[g]indol-1-yl)-1-methylethylamine, 0.74 g (7.3 mmol) of triethylamine and 1.04 g (7.3 mmol) of ethyl ether triperoxonane acid in 100 ml of anhydrous methanol was stirred for 27 h at room temperature. After removal of the solvent in vacuo the residue was dissolved in 100 ml of anhydrous dioxane, was added 1.56 g (6.9 mmol) BCH and boiled for 1.5 h under reflux. Then the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (dichloromethane/acetone 4:1). The result was obtained 1.2 g (59%) of (S)-N- [2-(8 - methoxy-1H-Benz[g]indol-1-yl)-1-methylethyl] -trifurcated in the form of a light brown solid substance, which without further recrystallization was used in subsequent reactions.

b) a Mixture of 1.2 g (3.4 mmole) of (S)-N-[2-(8-methoxy-1H - Benz[g]indol-l-yl)-1-methylethyl] -trifurcated, 1.2 g (21 mmol) of potassium hydroxide in 3 ml of water and 50 ml of methanol was heated for 3 h under reflux. Then the reaction mixture was poured into 100 ml of 1H sodium liquor, and was twice extracted with respectively 100 ml of diethyl ether and once with 100 ml of ethyl acetate, the combined organic phases are once washed with 150 ml saturated sodium chloride solution and dried over magnesium sulfate. After concentration and a solution of 398 mg (3.4 mmole) of fumaric acid in 30 ml of methanol. Then was stirred for 16 h at room temperature, then was filtered white crystals. As a result received 780 mg (73%) fumarata (S)-2-(8 - methoxy-1H-Benz[g]indol-1-yl)-1-methylethylamine (1:0,5) so pl. 208o.

Example 8

a) a Solution of 9.1 g (48.3 mmole) of 6-ethyl-3,3-dimethyl-1-indanone 9,98 ml (0.12 moles) of Z-butene-2-ol and 250 mg of p-toluenesulfonic acid in 100 ml of 2,2-dimethoxypropane for 88 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 6:1). As a result, along with 2.0 g of educt received 8,2 g (70%) of (RS)-2-(2-butene-1 - yl)-6 - ethyl-3,3-dimethyl-1-indanone as a yellow oil.

b) cooled to -70oa solution of 8.2 g (33.8 mmol) of (RS)-2-(2 - butene-1-yl)-6-ethyl-3,3-dimethyl-1-indanone in 120 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition and 3.72 ml (50.7 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in HAC is ivali for 2 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding at the tip of a spatula sodium bicarbonate. After this was added 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrate - tribali in vacuum. The result has been of 7.55 g (97%) of (RS)-2-(2 - oxoethyl)-6-ethyl-3,3-dimethyl-1-indanone in the form of a yellowish oil.

C) a Solution of 2.3 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-ethyl-3,3 - dimethyl-1-indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 40 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 3:2). The result has been of 2.45 g (91%) of (R)-1-(7-ethyl-4,4-dimethyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a red oil.

g) cooled to 0oa solution of 2.4 g (8,91 mmol) of (R)-1-(7-ethyl - 4,4-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and equal to 4.97 ml (35.6 mmol) of the Tr and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases are washed with 90 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 50 ml of anhydrous dimethylformamide, treated of 1.16 g (17.8 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 70 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and the solution was concentrated in vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/diethyl ether 4:1). The result obtained 1.44 g (55%) of (S)-1-(2 - azithromy)-7-ethyl-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of oil red.

d) 1.44 g (4,89 mmole) of (S)-1-(2-azithromy)-7-ethyl-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrole, rectorville from catalyst washed with ethanol and the solution is kept in vacuum. The obtained colorless oil was dissolved in 120 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 568 mg (4,89 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered white crystals. The result was obtained 1.04 g (55%) fumarata (S)-2-(7 - ethyl-4,4 - dimethyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:1) with so pl. 178o.

Example 9

a) a Solution of 10.0 g (56.1 mmol) of 6-fluoro-3,3-dimethyl-1-indanone, 11,1 ml (0,13 mol) C-butene-2-ol and 200 mg of p-toluenesulfonic acid in 200 ml of 2,2-dimethoxypropane within 96 h was boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 8:1). As a result, along with 11.9 g of educt got to 3.38 g (26%) of (RS)-2-(2-butene-1-yl)-6-fluoro - 3,3-dimethyl-1-indanone as a yellow oil.

b) cooled to -70othe solution to 3.38 g (14.6 mmol) of (RS)-2- (2-butene-1-yl)-6-fluoro-3,3-dimethyl-1-indanone in 75 ml of anhydrous dichloromethane and 15 ml of anhydrous methanol under stirring missed during the course the m After addition of 1.6 ml (to 21.8 mmol) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 40 ml of dichloromethane and, after addition of 5 ml water and 5 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 90 ml of water and neutralized with stirring, adding with a spatula sodium bicarbonate. Next was added 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 3.04 from g (95%) of (RS)-2-(2 - oxoethyl)-6-fluoro-3,3-dimethyl-1-indanone in the form of a yellowish oil.

C) a Solution of 3.04 from g (13.8 mmol) of (RS)-2-(2-oxoethyl)-6-fluoro-3,3 - dimethyl-1-indanone and 110 mg of p-toluenesulfonic acid in 100 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution to 4.14 g (55.2 mmol) of (R)-1-amino-2-propanol in 40 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl is in the form of a brown oil.

g) cooled to 0oa solution of 2.0 g (8.15 mmol) of (R)-1-(7-fluoro - 4,4-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 4.52 ml (32.6 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise to 1.27 ml (16.3 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 60 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 50 ml of anhydrous dimethylformamide, and treated with 1.07 g (16.3 moles) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o. After cooling the solution was poured into 30 80 ml of water and was extracted three times respectively portions 70 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and the solution was concentrated in vacuum. Received measles is dipropyl)-7-fluoro - 4,4-dimethyl-1,4-dihydroindeno[1,2-b]pyrrole as a yellow oil.

d) 1.22 g (4,29 mmole) of (S)-1-(2-azithromy)-7-fluoro-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 120 mg of platinum oxide for 2 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 150 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 498 mg (4,29 mmole) of fumaric acid in 20 ml of methanol. Then continued to stir for 15 h at room temperature, then was filtered white crystals. The result obtained 1.12 g (70%) fumarata (S)- 2-(7-fluoro-4,4-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methyl - ethylamine (1:1) with so pl. 211o.

Example 10

a) a Solution of 14.2 g (97.3 mmol) of 6-methyl-1-indanone, 20,1 ml (to 0.23 mole) of 3-butene-2-ol and 140 mg of p-toluenesulfonic acid in 140 ml of 2,2 - dimethoxypropane boiled under reflux for 69 hours in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result has been 16.3 g (83%) of (RS)-2-(2-butene-1-yl)-6-methyl-1-indanone as a yellow m is 00 ml of anhydrous dichloromethane and 60 ml of anhydrous methanol under stirring missed during 80 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 8.95 ml (122 mmole) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 300 ml of dichloromethane and, after addition of 40 ml water and 40 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 200 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 100 ml of water, the phases were separated and the aqueous phase was extracted twice respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The resulting crude product was recrystallized from diethyl ether/hexane. The result obtained 12.7 g (82%) of (RS)-2-(2 - oxoethyl)-6-methyl-1-indanone as a yellow solid with so pl. 53 - 54o.

C) the Solution 2,82 g (15 mmol) of (RS)-2-(2-oxoethyl)-6-methyl-1 - indanone and 100 mg p-toluenesulfonic acid in 100 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution 4,51 g (60 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued CIP by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result was obtained 2.7 g (79%) of (R)-1-(7-methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown-green oil.

g) cooled to 0oa solution of 2.7 g (11.9 mmol) of (R)-1-(7-methyl - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 6.7 ml (47,6 mmol) of triethylamine in 75 ml of dichloromethane under stirring was added dropwise 1.8 ml (23,8 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml dichloromethane, washed twice respectively portions 90 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 90 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 70 ml of anhydrous dimethylformamide, and treated with 1.55 g (of 23.8 mmole) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 150 ml of water and was extracted twice respectively in portions of 150 ml of ethyl acetate. The combined organic phases are washed once respectively 120 ml of water and 120 ml on the second brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 1.5 g (50%) of (S)-1-(2-azithromy)-7-methyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of a yellowish oil.

d) 1.5 g (5,94 mmol) of (S)-1-(2-azithromy)-7-methyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 150 mg of platinum oxide for 4 hours and Then the catalyst was filtered off, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 150 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 345 mg (2.97 mmole) of fumaric acid in 25 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered white crystals. The result was obtained 1.1 g (65%) fumarata (S)-2-(7-methyl-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 194o.

Example 11

a) a Solution of 10.0 g (47.4 mmol) of 6-bromo-1-indanone 9,79 ml of 0.11 mol) of 3-butene-2-ol and 100 mg of p-toluenesulfonic acid in 100 ml of 2,2 - dimethoxypropane for 71 h was heated under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl LASS="ptx2">

b) cooled to -70othe solution 9,86 g (37.2 mmol) of (RS)-2-(2 - butene-1-yl)-6-bromo-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed for 60 minutes a stream of ozone (2 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 4.09 to ml (55.8 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 150 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The resulting crude product was recrystallized from ethyl acetate/hexane. The result was obtained 7.5 g (80%) of (RS)-2-(2-oxoethyl)-6-bromo-1-indanone as a yellowish solid with so pl. 84o.

C) a Solution of 2.0 g (7.9 mmol) of (RS)-2-(2-oxoethyl)-6-bromo-1-indanone and 80 mg of p-Tolu is NML) was added a solution of 2.37 g (of 31.6 mmol) of (R)-1-amino-2-propanol in 10 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 4:1). The result obtained 1.19 g (52%) of (R)-1-(7-bromo-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.19 g (4,07 mmole) of (R)-1-(7-bromo - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and of 2.27 ml (16.3 mmol) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise 0.63 ml (8,14 mmol) methanesulfonanilide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The oil obtained green was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.53 g (8,14 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the major organic phase was washed once each respectively 100 ml of water and 100 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.95 g (74%) of (S)-1-(2-azithromy)-7-bromo-1,4-dihydroindeno[1,2-b]pyrrole as a colorless oil.

d) 0.95 g (2,99 mmole) of (S)-1-(2-azithromy)-7-bromo-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 95 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The mixture of products was separated on silica gel (methanol/dichloromethane 5:95). The obtained colorless oil (507 mg) was dissolved in 50 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 101 mg (of 0.87 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered white crystals. As a result received 503 mg (50%) fumarata (S)-2-(7-bromo-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 197o.

Example 12

a) a Solution of 22.0 g (101 mmol) of 6-methoxy-3,3-diethyl-1-indanone of 20.8 ml (0,24 mol) C-butene-2-ol and 220 mg of p-toluenesulfonic acid in 220 ml of 2,2-dimethoxypropane during which the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 6:1). As a result, along with 15.7 g of educt received 4,1 (15%) (RS)-2-(2-butene-1-yl)-6 - methoxy-z,Z-diethyl-1-indanone as a yellow oil.

b) cooled to -70oa solution of 4.1 g (15,2 moles) of (RS)-2-(2 - butene-1-yl)-6-methoxy-3,3-diethyl-1-indanone in 60 ml of anhydrous dichloromethane and 15 ml of anhydrous methanol under stirring missed for 25 min stream of ozone (2 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 1.66 ml (22,6 mmole) of dimethyl sulfide was stirred for 22 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 50 ml of dichloromethane and, after addition of 8 ml of water and 8 ml triperoxonane acid was stirred for 2.5 h at room temperature. Then the mixture was poured into 70 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been a 3.9 g (99%) of (RS)-2-(2-oxoethyl)-6-methoxy-3,3-diethyl-1-indanone in the form of a yellowish oil.

C) a Solution of 3.9 g (15 mmol) in water separator. In the boiling solution for 5 min was added dropwise a solution of 4.5 g (60 mmol) of (R)-1-amino-2-propanol in 30 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:1). The result has been 2,73 g (61%) of (R)-1-(7-methoxy-4,4 - diethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol in the form of oil red-brown color.

g) cooled to 0othe solution 2,73 g (9,12 mmol) of (R)-1-(7 - methoxy-4,4-diethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 5.08 ml (36.5 mmol) of triethylamine in 70 ml of dichloromethane under stirring was added dropwise to 1.42 ml (18.2 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml be Agrawal for 15 h 60o. After cooling the solution was poured into 70 ml of water and was extracted three times respectively with 80 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 80 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). The result has been 2,33 g (79%) of (S)- 1-(2-azithromy)-7-methoxy-4,4-diethyl-1,4-dihydroindeno [1,2-b] pyrrole as a yellow oil.

d) 2.25 g (6,94 mmol) of (S)-1-(2-azithromy)-7-methoxy-4,4-diethyl-1,4-dihydroindeno [1,2-b]pyrrole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 225 mg of platinum oxide for 2 hours and Then the catalyst was filtered off, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring 406 mg (3.5 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered white crystals. The result has been of 1.93 g (78%) fumarata (S)-2-(7-methoxy-4,4 - diethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-the (of 0.32 mole) of 3-butene-2-ol and 200 mg of p-toluenesulfonic acid in 200 ml of 2,2-dimethoxypropane for 63 h boiled under reflux in a water separator, filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). The result has been to 18.6 g (68%) of (RS)-2-(2-butene-1-yl)-5-fluoro-1-indanone as a yellow oil.

b) cooled to -70oa solution of 18.5 g (90,6 mmol) (RS)-2-(2 - butene-1-yl)-5-fluoro-1-indanone in 300 ml of anhydrous dichloromethane and 50 ml of anhydrous methanol under stirring missed within 85 minutes a stream of ozone (3.5 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 9.9 ml (135 mmol) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 220 ml of dichloromethane and, after addition of 40 ml water and 40 ml triperoxonane acid was stirred for 4.5 hours at room temperature. Then the mixture was poured into 170 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this there was added 110 ml of water, the phases were separated and the aqueous phase was twice extracted portions respectively in 170 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentration is as a result received of 13.6 g (78%) of (RS)-2-(2 - oxoethyl)-5-fluoro-1-indanone in the form of a yellowish solid substance with so pl. 56o.

C) the Solution is 2.88 g (15 mmol) of (RS)-2-(2-oxoethyl)-5-fluoro-1-indanone and 100 mg p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. The boiling solution was added dropwise over 5 min a solution 4,51 g (60 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been a 2.75 g (79%) of (R)-1-(6-fluoro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a brown oil.

g) cooled to 0oa solution of 2.75 g (11.9 mmol) of (R)-1-(6-Fluoro - 1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-propan-2-ol and 6.7 ml (47,6 mmol) of triethylamine in 70 ml of dichloromethane under stirring was added dropwise 1.8 ml (23,8 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 90 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 90 ml of dichloromethane. The combined organic phases are washed with 100 ml of saturated dissolved in 60 ml of anhydrous dimethylformamide, was treated with 1.55 g (12.5 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 80 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (toluene). The result has been to 1.23 g (40%) of (S)-1-(2-azithromy)-6-fluoro-1,4-dihydroindeno [1,2-b] pyrrole in the form of a yellowish oil.

d) of 1.23 g (4,80 mmole) of (S)-1-(2-azithromy)-6-fluoro-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 125 mg of platinum oxide for 6 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 130 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 279 mg (2,40 15 mmole) of fumaric acid in 25 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered white Krista is square 200o.

Example 14

a) a Solution of 13.2 g (63.4 mmole) of 6-phenyl-1-indanone, 11 ml of 0.13 mole) of 3-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2-dimethoxypropane within 48 h was boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result obtained 12.0 g (72%) of (RS)-2-(2-butene-1-yl)-6-phenyl-1-indanone in the form of a yellowish solid, which without additional recrystallization was used in subsequent reactions.

b) cooled to -70oa solution of 12.0 g (45.8 mmol) of (RS)-2-(2-butene-1-yl)-6-phenyl-1-indanone in 180 ml of anhydrous dichloromethane and 40 ml of anhydrous methanol under stirring passed within 75 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 5,04 ml (68.7 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 120 ml of dichloromethane and, after addition of 30 ml water and 30 ml triperoxonane acid was stirred for 2 h at room temperaturebased sodium. Then add another 50 ml of water, the phases were separated and the aqueous phase was extracted twice respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result was obtained 11.2 g (97%) of (RS)-2-(2-oxoethyl)-6-phenyl-1-indanone in the form of a yellowish oil.

C) a Solution of 2.5 g (10 mmol) of (RS)-2-(2-oxoethyl) -6-phenyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result was obtained 1.5 g (52%) of (R)-1-(7-phenyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a brown oil.

g) cooled to 0oa solution of 1.5 g (5.2 mmole) of (R)-1-(7-phenyl-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3 ml (20.8 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise of 0.82 ml (10.4 mmol) of methanesulfonamide and continued to stir for 1.5 h at is produced with 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The obtained solid green color was dissolved in 50 ml of anhydrous dimethylformamide, treated of 0.53 g (8.2 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 100 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 80 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.64 g (39%) of (S)-1-(2 - azithromy)-7-phenyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of a brown oil.

d) 0.64 g (2,04 mmole) of (S)-1-(2-azithromy)-7-phenyl-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 65 mg of platinum oxide for 2 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained solid greenish solution is I) fumaric acid in 20 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered beige crystals. The result has been 0,37 g (53%) fumarata (S)-2-(7 - phenyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 202 - 204o.

Example 15

a) a Solution of 16 g (108 mmol) of 6-hydroxy-1-indanone of 22.3 ml (of 0.26 mole) of Z-butene-2-ol and 160 mg p-toluenesulfonic acid in 170 ml of 2,2-dimethoxypropane for 38 h was heated under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). As a result, along with 7.5 g of educt received 6,21 g (28%) of (RS)-2-(2-butene-1-yl)-6-hydroxy-1-indanone as a yellow oil.

b) a Solution of 5.0 g (24.7 mmole) of (RS)-2-(2-butene-1-yl)-6-hydroxy-1-indanone with 4.1 ml (54,4 mmole) of ethylbromide, 6,83 g (49,4 mmole) of potassium carbonate and 10 ml of N,N-dimethylformamide in 70 ml of acetone was heated for 35 h, 35o. After cooling the solution was poured into 100 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, so-ethoxy-1-indanone as a red-brown oil, which is directly used in the subsequent reaction.

C) After cooled to -70oa solution of 5.6 g (24,3 mmole) of (RS)-2-(2-butene-1-yl)-6-ethoxy-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed over 90 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 2.72 ml (37.1 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. Then the reaction mixture was evaporated in vacuo, the residue was treated with 170 ml of dichloromethane and, after addition of 25 ml water and 25 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrate - tribali in vacuum. The result obtained 3.4 g (64%) of (RS)-2-(2 - oxoethyl)-6-ethoxy-1-indanone in the form of oil red-brown color.

g) a Solution of 1.6 g (7.33 mmol) of (RS)-2-(2-oxoethyl)-6-ethoxy-1 - indanone and 70 mg of p-colorcapable a solution of 2.2 g (29.3 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 4:1). The result has been of 1.03 g (52%) of (RS)-1-(7-ethoxy-1,4 - dihydroindeno [1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

d) cooled to 0oa solution of 1.03 g (3.8 mmole) of (RS)-1-(7 - ethoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.1 ml (15.2 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise a 0.59 ml (7.6 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 30 ml of anhydrous dimethylformamide, and treated with 0.6 g (9.2 mmol) of sodium azide and the reaction mixture under stirring was heated for 20 h 60o. After cooled the major organic phase was washed once each respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (ethyl acetate/hexane 1:10). As a result received 948 mg (72%) of (RS)-1-(2-azithromy)-7-ethoxy-1,4-dihydroindeno[1,2-b]pyrrole in the form of a yellowish oil.

e) 0,94 g (3.32 mmole) of (RS)-1-(2-azithromy)-7-ethoxy-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 80 ml of anhydrous ethanol, was first made in the presence of 94 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 198 mg (1.7 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered white crystals. As a result received 581 mg (56%) fumarata (RS)-2-(7-ethoxy - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 212 - 214o.

Example 16

a) a Solution 4,74 g (21.6 mmole) of (RS)-2-(2-butene-1-yl)-6-hydroxy-1-indanone, 5,18 ml, or 47.6 mmol) of isobutylamine and 5,98 g (43,3 mmole) of potassium carbonate in 40 ml of N,N-dimethylformamide was heated for 48 h to 60o. According to the ATA. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The result has been to 5.2 g (93%) of (RS)-2-(2-butene-1-yl)-6-isobutoxy-1-indanone as a brown oil, which was directly used in the subsequent reaction.

b) cooled to -70oa solution of 5.1 g (19.7 mmol) of (RS)-2-(2 - butene-1-yl)-6-isobutoxy-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed over 90 min stream of ozone (2 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 2.16 ml (29.4 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 170 ml of dichloromethane and, after addition of 25 ml water and 25 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. With 3 g (48%) of (RS)-2-(2-oxoethyl)-6-isobutoxy-1-indanone as a red-brown oil.

C) a Solution of 2.3 g (9.34 mmol) of (RS)-2-(2-oxoethyl)-6-isobutoxy-1-indanone and 70 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.93 g (37.3 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:4).

The result has been 1.52 g (57%) of (RS)-1-(7-isobutoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)- propan-2-ol in the form of a brown oil.

g) cooled to 0oa solution of 1.5 g (5,26 mmol) (RS)-1-(7 - isobutoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 2.93 ml (21,0 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 0,81 ml (10.5 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed the green circle oil was dissolved in 30 ml of anhydrous dimethylformamide, was treated with 0.68 g (10.5 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 100 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (ethyl acetate/hexane 1:4). The result has been 0,43 g (26%) (RS) -1 -(2-azithromy)-7-isobutoxy-1,4-dihydroindeno [1,2-b] pyrrole in the form of a slightly yellowish oil.

d) of 0.43 g (1,38 mmole) of (RS)-1-(2-azithromy)-7-isobutoxy-1,4 - dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 50 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 70 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 80 mg (0,69 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 17 h at room temperature, after che is about[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 178o.

Example 17

a) a Solution of 11.8 g (73.7 mmole) of 6-ethyl-1-indanone of 15.4 ml of 0.18 mol) of 3-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2 - dimethoxypropane for 46 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result has been a 7.92 g (50%) of (RS)-2-(2-butene-1-yl)-6-ethyl-1-indanone as a brown oil.

b) cooled to -70osolution a 7.92 g (37,0 mmol) (RS)-2-(2 - butene-1-yl)-6-ethyl-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After addition to 3.36 ml (45.8 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 150 ml of dichloromethane and, after addition of 30 ml water and 30 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding using spatially respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 6,94 g (93%) of (RS)-2-(2-oxoethyl)-6-ethyl-1-indanone as a yellow oil.

C) the Solution 2,02 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-ethyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1).

The result was obtained 1.7 g (71%) of (R)-1-(7-ethyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.7 g (? 7.04 baby mortality mmol) of (R)-1-(7-ethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.9 ml (28,2 mmol) of triethylamine in 55 ml of dichloromethane under stirring was added dropwise 1.1 ml (14.1 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml saturated the and. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 50 ml of anhydrous dimethylformamide was treated with 0.84 g (12.8 mmol) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o. After cooling the mixture was poured into 120 ml of water and was extracted twice respectively portions 120 ml of ethyl acetate. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 0.74 g (40%) of (S)-1-(2-azithromy)-7-ethyl-1,4-dihydroindeno[1,2-b]pyrrole as a yellow oil.

d) 0.74 g (2.7 mmole) of (S)-1-(2-azithromy)-7-ethyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 80 mg of platinum oxide for 15 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and the and for 17 h at room temperature, then was filtered white crystals. The result was obtained 0.45 g (56%) fumarata (S)-2-(7-ethyl - 1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 189 - 190o.

Example 18

a) a Solution of 8 g (42 mmole) of 6-methoxycarbonyl-1-indanone, 8 ml of 0.1 mol) C-butene-2-ol and 100 mg of p-toluenesulfonic acid in 80 ml of 2,2 - dimethoxypropane boiled under reflux for 28 h in the water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 3:1). As a result, along with 1.3 g of educt was obtained 8.5 g (83%) of (RS)-2-(2-butene-1-yl)-6-methoxycarbonyl-1-indanone in the form of a yellow oil.

b) cooled to -70oa solution of 10.5 g (42,9 mmole) of (RS)-2-(2-butene-1-yl)-6-methoxycarbonyl-1-indanone in 150 ml of anhydrous dichloromethane under stirring missed for 45 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 4,74 ml (64.4 mmole) of dimethyl sulfide was stirred for 18 h at room temperature. The reaction mixture was evaporated in vacuum and purified by column chromatography on silica gel (dieti the carbonyl-1 - indanone as a yellowish solid with so pl. 92o.

C) the Solution 2,32 g (10 mmol) of (RS)-2-(2-oxoethyl)-6 - methoxycarbonyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result was obtained 2.2 g (81%) of (RS)-l-(7-methoxycarbonyl-l,4 - 30 dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol in the form of a brown oil.

g) cooled to 0oa solution of 2.2 g (8.1 mmol) of (RS)-1-(7 - methoxycarbonyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 4,55 ml (32,4 mmole) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise of 1.26 ml (16.2 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. United'or is in a vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated of 1.05 g (16.2 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 100 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are once washed with 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 950 mg (40%) of (RS)-1-(2-azithromy)-7-methoxycarbonyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of a brownish oil.

d) 0.95 g (3.2 mmole) of (RS)-1-(2-azithromy)-7-methoxycarbonyl-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 70 ml of anhydrous methanol, was first made in the presence of 95 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with methanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 110 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 186 mg (1.6 mmole) of fumaric acid in 20 ml methanolate received 770 mg (73%) fumarata (RS)-2-(7-methoxycarbonyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 199 - 200o.

Example 19

a) cooled to 0oa solution of 3.55 g (10.7 mmol) of (RS)-1-(2 - azithromy)-7-methyloxycarbonyl-1,4-dihydroindeno [1,2-b] pyrrole in 90 ml of anhydrous diethyl ether and 90 ml of anhydrous tetrahydrofuran for 5 min was added dropwise by 5.87 ml (11.7 mmol) of a 2M solution penility. After 15 min at the same temperature again was added dropwise by 5.87 ml finelite and stirred for 5 min, after which the reaction mixture was treated with 50 ml of saturated solution of ammonium chloride and 25 ml of water. Then once were extracted with 50 ml ethyl acetate, the aqueous phase was slightly acidified using 1N hydrochloric acid and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are once washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The result was obtained 2.7 g (99%) of (RS)-1-(2-azithromy)-7-hydroxy-1,4-dihydroindeno [1,2-b] pyrrole as a brown oil.

b) In a solution of 1.05 g (4,13 mmole) of (RS) -1- (2-azithromy)-7 - hydroxy-1,4-dihydroindeno[1,2-b] pyrrol and 0.6 ml (7.4 mmol) of pyridine in 30 ml of dichloromethane under stirring was added 0.7 ml (7.4 mmol) of acetanhydride and continued to stir Jesu and washed once with 50 ml saturated solution of sodium chloride. After drying over magnesium sulfate then concentrated in vacuo and the crude product was purified by column chromatography on silica gel (ethyl acetate/hexane 1:2). The result was obtained 0.9 g (85%) of (RS)-1-(2-azithromy)-7 - acetoxy-1,4-dihydroindeno[1,2-b]pyrrole in the form of oil slightly orange color.

in) 0.84 g (2,84 mmole) of (RS)-1-(2-azithromy)-7-acetoxy-1,4 - dihydroindeno[1,2-b] pyrrole dissolved in 100 m of anhydrous ethanol, was first made in the presence of 85 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 178 mg (1,54 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 4 h at room temperature, then was filtered white crystals. The result obtained 400 mg (43%) fumarata (RS)-2-(7 - acetoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 187 - 188o.

Example 20

a) a Solution of 1.88 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-methyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min dropwise domovladenie 45 min, moreover, the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been 0,99 g (44%) of (RS)-1-(7-methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

b) cooled to 0oa solution of 0.98 g (4.3 mmole) of (RS)-1-(7-methyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.4 ml (17.2 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 0.67 ml (8.6 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 40 ml of anhydrous dimethylformamide, and treated with 0.56 g (8.6 mmol) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o. After cooling the solution was poured into 100 ml of water and twice the extras the memory 70 ml of water and 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has got 737 mg (68%) of (RS)-1-(2-azithromy)-7-methyl-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

in) 0.73 g (2,89 mmole) of (RS)-1-(2-azithromy)-7-methyl-1,4-dihydroindeno [1,2-b] -pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 75 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 168 mg (1,45 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered white crystals. The result was 596 mg (73%) fumarata (RS)-2-(7 - methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 194o.

Example 21

a) a Solution of 2.08 g (10 mmol) of (RS)-2-(2-oxyethyl)-6-chloro-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol the solvent was reduced to 30 ml The cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 3:7). The result has been 1.52 g (61%) of (RS)-1-(7-chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

b) cooled to 0oa solution of 1.52 g (6.1 mmol) of (RS)-1-(7-chloro - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.4 ml (24.5 mmole) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise to 0.95 ml (12.3 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 280 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 30 ml of anhydrous dimethylformamide, treated 718 mg (11.0 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling, the solution was poured stata. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 1.0 g (60%) of (RS)-1-(2-azithromy)-7-chloro-1,4-dihydroindeno [1,2-b] pyrrole in the form of butter.

b) 1.0 g (3.7 mmole) of (RS)-1-(2-azithromy)-7-chloro-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 100 mg of platinum oxide for 17 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 75 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 195 mg (1.68 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 19 h at room temperature, then was filtered white crystals. As a result received 945 mg (85%) fumarata (RS)-2-(7 - chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 206o.

Example 22

a) a Solution of 2 g (9.8 mmol) of (RS)-2-(2-oxoethyl)-6-methoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 70 ml of bezvodnoe) (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result was obtained 1.7 g (71%) of (RS)-1-(7-methoxy-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a solid substance with so pl. 76o.

b) cooled to 0oa solution of 1 g (4.1 mmole) of (RS)-1-(7-methoxy-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2,3 ml (16.4 mmol) of triethylamine in 30 ml of dichloromethane under stirring was added dropwise of 0.64 ml (8.2 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.53 g (8.2 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h is about 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). As a result received 750 mg (68%) of (RS)-1-(2-azithromy)-7-methoxy - 1,4-dihydroindeno [1,2-b]pyrrole as a colorless oil.

C) 1 g (3.7 mmole) of (RS)-1-(2-azithromy)-7-methoxy-1,4 - dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 100 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 216 mg (1.8 mmole) of fumaric acid in 20 ml of methanol. Then continued to stir for 18 h at room temperature, then was filtered white crystals. As a result received 882 mg (79%) fumarata (RS)-2-(7-methoxy - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 203o.

Example 23

a) a Solution of 20.0 g (0.12 moles) of 6-methoxy-1-indanone, 31,3 ml of 0.36 mol) C-butene-2-olomouce a mixture of methanol/acetone was evaporated and the reaction solution was heated overnight under reflux. After cooling, the solution was washed with 500 ml of saturated solution of sodium bicarbonate. The aqueous phase was extracted with 50 ml ethyl acetate, the combined organic phase was dried with magnesium sulfate and evaporated in vacuum. After purification on silica gel (hexane/diethyl ether 5:1) got to 13.6 g (55%) of (RS)-2-(2-butene-1-yl)-6-methoxy-1-indanone in the form of light yellow oil.

b) cooled to -70oa solution of 13.6 g (62 mmole) of (RS)-2-(2-butene-1-yl)-6-methoxy-1-indanone in 200 ml of anhydrous dichloromethane and 400 ml of anhydrous methanol under stirring missed within 60 min ozone (3 g ozone/hour). Then the solution was purged with oxygen, after which the cold solution was added 6.4 ml (87 mmol) of dimethyl sulfide. During the night the temperature of the solution reached room temperature and then the solution was evaporated in vacuum. The residue was dissolved in 1600 ml of dichloromethane, the solution was treated with 600 g of silica gel and 100 ml of a 10% solution of oxalic acid and was stirred overnight. Then filtered and concentrated in vacuum. The result obtained 6.5 g (51%) of (RS)-2-(2-oxoethyl)-6-methoxy-1-indanone as a yellow oil.

C) a Solution of 4.5 g (22 mmole) of (RS)-2-(2-oxoethyl)-6-methoxy-1-indanone and 2.3 g (22 mmole) of N-acetylethylenediamine in 100 ml of toluene was boiled in t is I use magnesium sulfate and re-evaporated. After purification on silica gel (ethyl acetate) was obtained 0.9 g (15%) of N- [2-(7-methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-ethyl] -ndimethylacetamide in a solid yellow color.

g) 2.4 g (8.9 mmol) of N-[2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol - 1-yl)-ethyl] -ndimethylacetamide was heated in an argon atmosphere in 48 ml of ethylene glycol/water 2: 1 in the presence of 2.5 g of potassium hydroxide for 17 h to 140o. Then cooled and treated with 250 ml Polynesians solution of sodium chloride. After it was extracted three times with diethyl ether, the United extracts were dried over sodium sulfate, filtered and evaporated. The brown oil was dissolved in 30 ml of methanol and was treated with 1.0 g (8.6 mmol) of fumaric acid, which was accompanied by loss of light brown crystals. These crystals were dissolved in 120 ml of warm methanol. After cooling to room temperature the product was led by the slow addition of 120 ml of diethyl ether. The result was obtained 2.0 g (66%) fumarata 2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-ethylamine (1:1) with so pl. 177 - 180o.

Example 24

a) a Solution of 2.0 g (10.4 mmol) of (RS)-2-(2-oxoethyl)-5-fluoro-1-indanone and 85 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In boiling p is A. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2:3). The result has been 1.66 g (69%) of (RS)-1-(6-fluoro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

b) cooled to 0oa solution of 1.66 g (7,17 mmol) (RS)-1-(6-fluoro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.98 ml (28.7 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise to 1.12 ml (14.3 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 70 ml of dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated 0,82 g (12.5 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After ohlazhdeniya the organic phase was washed once each respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.45 g (24%) of (RS)-1-(2-azithromy)-6-fluoro - 1,4-dihydroindeno[1,2-b]pyrrole as a yellow oil.

in) of 0.44 g (1,71 mmol) of (RS)-1-(2-azithromy)-6-fluoro-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 45 mg of platinum oxide for 5 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 40 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 100 mg (0,86 mmole) of fumaric acid in 7 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered white crystals. The result has been 0.39 g (80%) fumarata (RS)-2-(6-fluoro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 202o.

Example 25

a) a Solution of 10.6 g (63,3 mmole) of 5,6-debtor-1-indanone of 13.1 ml (0,15 mol) C-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2 - dimethoxypropane for 64 h boiled under reflux in a water separator filled molecules chromatography on silica gel (hexane/diethyl ether 2:1). As a result, along with 3.6 g of educt received 5.32 g (38%) of (RS)-2-(2-butene-1-yl)-5,6-debtor-1-indanone as a brown oil.

b) cooled to -70oa solution of 5.3 g (of 23.8 mmole) of (RS)-2-(2 - butene-1-yl)-5,6-debtor-1-indanone in 125 ml of anhydrous dichloromethane and 25 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (2 g ozone/hour). Then the solution for 5 min was purged with oxygen for 10 min with argon. After the addition of 2.64 ml (36 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 60 ml of dichloromethane and, after addition of 10 ml water and 10 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 80 ml of water and neutralized with stirring, adding with a spatula sodium bicarbonate. After this was added 40 ml of water, the phases were separated and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. Thus was obtained a yellow oil, which was led from diethyl ether/hexane. The result has been 3,82 g (76%) of (RS)-2-(2-oxoethyl)-5,6-debtor-1-ind is debtor-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result obtained 1.13 g (45%) of (R)-1-(6,7-debtor-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a solid brown color, which without further recrystallization was used in subsequent reactions.

g) cooled to 0oa solution of 1.13 g (4.5 mmole) of (R)-1-(6,7-debtor-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.48 ml (18 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 0.7 ml (9 mmol) of methanesulfonamide and continued to stir for 2 h at this temperature. Then the reaction mixture was diluted with 70 ml of dichloromethane, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 60 ml of dichloromethane. The combined organic phases are washed with 90 ml saturated sodium chloride solution, dried over magnesium sulfate, oparg (8.98 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 70 ml of water and was extracted three times respectively portions 70 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4: 1). The result has been 0.97 g (79%) of (S)-1-(2-azithromy)-6,7-debtor-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

d) 0.97 g (3.5 mmole) of (S)-1-(2-azithromy)-6,7-debtor-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 100 mg of platinum oxide for 18 h Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained solid white color was dissolved in 75 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 406 mg (3.5 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 22 h at room temperature, then was filtered white crystals. The result has been 0,78 g (61%) fumarata (S)-2-(6,7-debtor-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-dimethyl-1 - indanone 13.3 ml (0,15 mol) C-butene-2-ol and 300 mg of p - toluenesulfonic acid in 150 ml of 2,2-dimethoxypropane for 71 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 6:1). As a result, along with 2.25 g of educt was obtained 11.9 g (66%) of (RS)-2-(2-butene-1-yl)-5-chloro-6-methoxy-3,3-dimethyl-1-indanone as a yellowish solid with so pl. 86o.

b) cooled to -70oa solution of 11.9 g (42,7 mmole) of (RS)-2-(2-butene-1-yl)-5-chloro-6-methoxy-3,3-dimethyl-1-indanone in 160 ml of anhydrous dichloromethane and 40 ml of anhydrous methanol under stirring missed during 50 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 4.7 ml (64 mmole) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 120 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding using was garofali respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The resulting oil was led from hexane/ethyl acetate. The result obtained 10.3 g (90%) of (RS)-2-(2 - oxoethyl)-5-chloro-6-methoxy-3,3-dimethyl-1-indanone as a yellowish solid with so pl. 102 - 103o.

C) the Solution to 6.67 g (25 mmol) of (RS)-2-(2-oxoethyl)-5-chloro-6-methoxy-3,3-dimethyl-1-indanone and 150 mg of p-toluenesulfonic acid in 200 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 7.51 g (0,1 mole) of (R)-1-amino-2-propanol in 40 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 40 ml of the Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:1). The result was obtained 7.0 g (92%) of (R)-1-(6 - chloro-7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.84 g (6.0 mmol) of (R)-1-(6-chloro-7 - methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-propan-2-ol and at 3.35 ml (24 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise with 0.93 ml (12 mmol) of methanesulfonamide and continued peremeci mawali respectively portions 90 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 90 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The oil obtained green was dissolved in 50 ml of anhydrous dimethylformamide, treated 0,78 g (12 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 3:1). The result has been 1,58 g (80%) of (S)-1-(2-azithromy)-6-chloro-7-methoxy-4,4-dimethyl-1,4 - dihydroindeno[1,2-b]pyrrole in the form of a red oil.

d), 1.56 g (4,72 mmole) of (S)-1-(2-azithromy)-6-chloro-7-methoxy-4,4-dimethyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 160 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The resulting oil jeltovatogo 548 mg (4,72 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 19 h at room temperature, then was filtered yellowish crystals. The result has been of 1.57 g (80%) fumarata (S)-2-(6 - chloro-7-methoxy-4,4-dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine (1:1) with so pl. 186 - 188o.

Example 27

a) a Solution of 1.92 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-fluoro-1 - indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (S)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2:3). The result obtained 1.51 g (65%) of (S)-1-(7-fluoro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

b) cooled to 0oa solution of 1.51 g (6.5 mmol) of (S)-1-(7-fluoro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and of 3.64 ml (26.1 mmol) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise 0.51 ml (13.1 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture Rabaul the sodium and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 30 ml of anhydrous dimethylformamide, treated 711 mg (10.9 mmol) of sodium azide and the reaction mixture under stirring was heated for 16 h to 50o. After cooling the solution was poured into 110 ml of water and was extracted twice respectively portions 110 ml of ethyl acetate. The combined organic phases are washed once respectively 90 ml of water and 90 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (toluene). As a result received 631 mg (38%) of (R)-1-(2-azithromy)-7-fluoro-1,4 - dihydroindeno[1,2-b]pyrrole in the form of butter.

in) 620 mg (2,4-mmole) of (R)-1-(2-azithromy)-7-fluoro-1,4 - dihydroindeno[1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 62 mg of platinum oxide for 15 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 75 ml of anhydrous diethyl ether, filtroil for 4.5 h at room temperature, then was filtered white crystals. As a result received 409 mg (53%) fumarata (R)-2-(7 - fluoro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:1) with so pl. 174o.

Example 28

a) a Solution of 2 g (9.8 mmol) of (RS)-2-(2-oxoethyl)-6-methoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution to 2.94 g (39.2 mmol) of (S)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result was obtained 1.5 g (63%) of (S)-1-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol - 1-yl)-propan-2-ol in the form of a solid substance with so pl. 74o.

b) cooled to 0oa solution of 1.5 g (6.2 mmol) of (S)-1-(7-methoxy - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.45 ml (approximately 24.6 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 0.96 ml (12.3 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 60 ml of anhydrous dimethylformamide, and treated with 0.71 g (10.9 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 1.0 g (60%) of (R)-1-(2-azithromy)-7-methoxy-1,4-dihydroindeno[1,2-b]pyrrole as a colorless oil.

C) 1 g (3.7 mmole) of (R)-1-(2-azithromy)-7-methoxy-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 100 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl is adopted in 20 ml of methanol. After this was stirred for 18 h at room temperature and then was filtered white crystals. As a result received 760 mg (68%) fumarata (R)-2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine (1:0,5) so pl. 207o.

Example 29

a) a Solution of 2.5 g (12.0 mmol) of (RS)-2-(2-oxoethyl)-6-chloro-1 - indanone and 100 mg p-toluenesulfonic acid in 120 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.6 g (47.9 mmol) of (S)-1-amino-1-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been, 1.56 g (53%) of (S)-1-(7-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

b) cooled to 0oa solution of 1.55 g (6.3 mmol) of (S)-1-(7-chloro-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-Alai 3.5 ml (25.0 mmol) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise to 0.97 ml (12.5 mmol) of methanesulfonamide and continued to stir for 1.5 h when this fact is 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 30 ml of anhydrous dimethylformamide, treated 815 mg (12.5 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of ethyl acetate. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil was purified by column chromatography on silica gel (toluene). As a result received 833 mg (49%) of (R)-1-(2-azithromy)-7-chloro-1,4 - dihydroindeno [1,2-b] pyrrole in the form of butter.

in) 750 mg (2.8 mmole) of (R)-1-(2-azithromy)-7-chloro-1,4-dihydroindeno [1.2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 75 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 70 ml of anhydrous diethyl ether, filtrative for 6 h at room temperature, then was filtered white crystals. As a result received 633 mg (76%) fumarata (R)-2-(7-chloro - 1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 195o.

Example 30

a) a Solution of 3 g (13.9 mmol) of (RS)-2-(2-oxoethyl)-7-methoxy-1 - tetralone and 150 mg of p-toluenesulfonic acid in 130 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 4.16 g (55.5 mmol) of (S)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 25 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result was obtained 3.0 g (84%) of (S)-1-(4,5-dihydro-8-methoxy-1H - Benz[g]indol-1-yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

b) cooled to 0oa solution of 3 g (11.7 mmol) of (S)-1-(4,5 - dihydro-8-methoxy-1H-Benz[g] indol-1-yl)-propan-2-ol and 6,55 ml (46.7 mmol) of triethylamine in 80 ml of dichloromethane under stirring was added dropwise 1.8 ml (23,3 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 300 ml Diethyleneamine the aqueous phase once was extracted with 100 ml diethyl ether. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The resulting oil was dissolved in 70 ml of anhydrous dimethylformamide, and treated with 1.52 g (23,3 mmole) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been to 1.9 g (58%) of (R)-1-(2-azithromy)-4,5-dihydro-8 - methoxy-1H-Benz[g] indole in the form of a yellowish oil.

in) of 1.9 g (6.4 mmol) of (R)-1-(2-azithromy)-4,5-dihydro-8-methoxy-1H-Benz[g] indole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 190 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The result has been 1.64 g (95%) of (R)-2-(4,5-dihydro-8-methoxy-1H - Benz[g]indol-1-yl)-1-methylethylamine and treated under stirring with a solution of 200 mg (1.7 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 2 h at room temperature, then was filtered white crystals. As a result received 450 mg (70%) fumarata (R)-2-(4,5-dihydro-8-methoxy - 1H-Benz[g]indol-1-yl)-1-methylethylamine (1:1) with so pl. 194o.

Example 31

a) a Solution of 1.2 g (4.7 mmole) of (R)-2-(4,5-dihydro-8-methoxy-1H - Benz[g]indol-1-yl)-1-methylethylamine, 0.52 g (5.1 mmol) of triethylamine and 0,83 g (5.8 mmol) of ethyl ether triperoxonane acid in 50 ml of anhydrous methanol was stirred for 27 h at room temperature. After removal of the solvent in vacuo the residue was dissolved in 70 ml of anhydrous dioxane, was added 1,8 (7.9 mmol) BCH and boiled for 1.5 h under reflux. Then the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (dichloromethane/acetone 4:1). The result has been 0.97 g (59%) of (R)-N-[2-(8 - methoxy-1H-Benz[g]indol-1-yl)-1-methylethyl] -trifurcated in the form of a light brown solid, which without further recrystallization was used in subsequent reactions.

b) a Mixture of 0.97 g (2.8 mmole) of (R)-N-[2-(8-methoxy-1H-Benz[g]indol-1 - yl)-1-methylethyl] -trifurcated, 1 g (17.8 mmol) of potassium hydroxide, 2 ml of water and 40 ml of methanol was heated for 15 h with obtendo with 80 ml of diethyl ether and once with 80 ml of ethyl acetate, the combined organic phases are once washed with 120 ml of saturated solution of sodium chloride and dried over magnesium sulfate. After concentration in vacuo the residue was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 322 mg (2,77 mmole) of fumaric acid in 30 ml of methanol. Then was stirred for 3 h at room temperature, then was filtered white crystals. The result obtained 600 mg (69%) fumarata (R)-2-(8 - methoxy - 1H-Benz[g]indol-1-yl)-1-methylethylamine (1:0,5) so pl. 209o.

Example 32

a) 254 mg (1.0 mmol) N-[2-(4,5-dihydro-8-methoxy-1H-Benz[g]indol-1-yl)ethyl]-ndimethylacetamide in argon atmosphere was dissolved in 10 ml of dioxane, was added 238 mg (1.05 mmole) BCH and heated for 1 h under reflux. The precipitated crystals were removed by filtration, the filtrate was evaporated and the residue was chromatographically on 50 g of silica gel using methylene chloride/acetone in a ratio of 9: 1. As a result received 211 mg (83%) R-[2-(8 - methoxy-1H-benzo[g]idol-1-yl)ethyl]-ndimethylacetamide in the form of solids slightly yellowish color. TX (silica gel): Rf= 0,25 (methylene chloride/acetone 9:1).

6) 211 mg (or 0.83 mmole) of N-[2-(8-methoxy-1H-Benz[g]indol-1 - yl)ethyl]-ndimethylacetamide in argon atmosphere Nagravision the mixture was cooled and poured into 20 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 2 ml of methanol, after which was added 70 mg (0.6 mmole) of fumaric acid. After addition of 5 ml of diethyl ether, the crystals were filtered and recrystallized from 8,5 ml of methanol/DMF 16:1. As a result received 142 mg (53%) fumarata 2-(8-methoxy-1H - benzo[g]Inal-1-yl)-ethylamine (1:1) as white crystals with so pl. 200 - 201o.

Example 33

a) a Solution of 20 g (104 mmole) of 5,6-dimethoxy-1-indanone, a 21.5 ml of 0.25 mol) C-butene-2-ol and 200 mg of p-toluenesulfonic acid 21.5 ml of 2,2 - dimethoxypropane and 200 ml of anhydrous toluene for 24 h was heated under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 3:2). The result was obtained 6.8 g (27%) of (R)-2- (2-butene-1-yl)-5,6-dimethoxy-1-indanone as a yellow oil.

b) cooled to -70oa solution of 6.8 g (27.6 mmol) of (RS)-2-(2 - butene-1-yl)-5,6-dimethoxy-1-indanone in 100 ml of anhydrous dichloromethane and 20 ml of anhydrous methanol under stirring missed for 30 min flux is key 4 ml (54,3 mmole) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 250 ml of dichloromethane and, after addition of 10 ml water and 10 ml triperoxonane acid was stirred for 1.5 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then was added 70 ml of water, separated phase and the aqueous phase was twice extracted respectively portions 120 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from diethyl ether/hexane. The result obtained 4.7 g (73%) of (RS)-2-(2-oxoethyl)-5,6-dimethoxy-1-indanone as a yellowish solid with so pl. 122o.

C) a Solution of 2 g (8.5 mmol) of (RS)-2-(2-oxoethyl)-5,6-dimethoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.56 g (a 34.2 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/tol.

g) cooled to 0oa solution of 0.91 g (3.3 mmole) of (RS)-1-(1,4 - dihydro-6,7-dimethoxybenzene[1,2-b] pyrrol-1-yl)-propan-2-ol and 1.86 ml (13.4 mmol) of triethylamine in 25 ml of dichloromethane under stirring was added dropwise to the value of 0.52 ml (6.7 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 140 ml of dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.43 g (6.7 mmol) of sodium azide and the reaction mixture under stirring was heated for 15 h 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of ethyl acetate. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The resulting brown oil is Uchali 400 mg (40%) of (RS)-1-(2-azithromy)-1,4-dihydro-6,7-dimethoxybenzene[1,2-b] pyrrole in the form of oil, which without further purification was used in subsequent reactions.

d) 0.4 g (1.3 mmole) of (RS)-1-(2-azithromy)-1,4-dihydro-6,7-dimethoxybenzene [1,2-b] pyrrole dissolved in 20 ml of anhydrous ethanol, was first made in the presence of 40 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 25 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution to 62.2 mg (0.54 mmole) of fumaric acid in 5 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. In the received 314 mg (71%) fumarata (RS)-2-(1,4 - dihydro-6,7-dimethoxybenzene[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 203 - 205o.

Example 34

a) a Solution of 48 g (0,324 mole) 4-chromanone, 67 ml (0,78 mol) C-butene-2-ol and 500 mg of p-toluenesulfonic acid in 67 ml of 2,2-dimethoxypropane and 500 ml of anhydrous toluene was boiled for 46 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). The result has been to 24.7 g (38%) of (RS)-2-(2-butene-1-yl)-4-chromanone in the form of a yellow wodnego dichloromethane and 150 ml of anhydrous methanol under stirring missed for 2 h in a stream of ozone (3.5 g ozone/hour). Then the solution was purged for 5 min with oxygen for 15 min with argon. After the addition of 13.4 ml of 0.18 mol) of dimethyl sulfide was stirred for 20 h at room temperature. Then the reaction mixture was evaporated in vacuo, the residue was treated with 250 ml of dichloromethane and, after addition of 40 ml water and 40 ml triperoxonane acid was stirred for 4 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then was added 70 ml of water, the phases were separated and the aqueous phase was twice extracted respectively portions 120 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been an increase of 22.7 g (99%) 2-(2-oxoethyl)-4-chromanone in the form of a yellow oil, which without further purification was used in subsequent reactions.

C) a Solution of 1.9 g (10 mmol) of (RS)-2-(2-oxoethyl)-4-chromanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent carrascal). The result has been 1,82 g (79%) of (RS)- 1-(1,4-dihydro-[1]benzopyrano[4,3-b]pyrrol-1-yl)-propan-2-ol as a yellow oil.

g) cooled to 0othe solution is 1.82 g (7.9 mmol) of (RS)-1-(1,4-dihydro-[1] benzopyrano[4,3-b] pyrrol-1-yl)-propan-2-ol and 4.4 ml (31,7 mmole) of triethylamine in 50 ml of anhydrous dichloromethane under stirring was added dropwise to 1.23 ml (15.9 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 280 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases are washed with 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated of 1.03 g (15.9 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml ugme. The resulting brown oil was purified by column chromatography on silica gel (toluene). The result obtained 1.44 g (71%) of (RS)-1-(2-azithromy)-1,4-dihydro-[1] benzopyrano[4,3-b]pyrrole as a colorless oil.

d) 1.44 g (5.7 mmol) of (RS)-1-(2-azithromy)-1,4-dihydro-[1]benzopyrano[4,3-b] pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 150 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 329 mg (2,83 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. As a result received 1.42 g (88%) fumarata (RS)-1-(1,4 - dihydro-[1]benzopyrano[4,3-b] pyrrol-1-yl)-1-methylethylamine(1:0,5) so pl. 208 - 209o.

Example 35

a) cooled to -70othe solution 2,96 g (18.3 mmol) of 6-methoxy-1-indanone in 300 ml of anhydrous tetrahydrofuran under stirring was added dropwise a freshly prepared from 3,12 ml (22 mmole) of Diisopropylamine and 13.8 ml (22 mmole) of 1,6 H n-utility in hexane solution litigiosa the temperature, then for 10 min was added dropwise a solution 2,03 ml (20.2 mmol) of Z-chloro-2-butanone in 40 ml of anhydrous tetrahydrofuran. Within 30 min the reaction mixture was allowed to cool to 0oand then stirred for another 30 min at this temperature. Then the reaction mixture was poured into 150 ml of ice was added 150 ml of a saturated solution of sodium chloride and separated the organic phase. The aqueous phase is once was extracted with 400 ml of diethyl ether, the combined organic phases are once washed with 200 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The resulting oil red was purified by column chromatography on silica gel (hexane/diethyl ether 3:2). As a result, along with 0,93 g of educt received 1.56 g (37%) of racemic 6-methoxy-2-(3-oxo-2-butyl)-1-indanone as a yellow oil.

b) a Solution of 1.5 g (6,46 mmol) of racemic 6-methoxy-2-(3-oxo-2 - butyl)-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 1.94 g (25.8 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for another 85 minutes, and the volume of rasterimage (ethyl acetate/toluene 2:3). The result has been to 1.23 g (70%) of (R)-1-(7-methoxy - 2,3 - dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a yellow oil.

in) cooled to 0oa solution of 1.22 g (4.5 mmole) of (R)-1-(7-methoxy - 2,3-dimethyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.5 ml (18 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 0.7 ml (9.0 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 60 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.58 g (9.0 mmol) of sodium azide and the reaction mixture was heated for 18 h under stirring to 80o. After cooling the mixture was poured into 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of n is Noah brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.64 g (48%) of (S)-1-(2-azithromy)-7 - methoxy-2,3-dimethyl-1,4-dihydroindeno[1,2-b] pyrrole as blignault oil.

g) to 0.63 g (2.12 mmole) of (S)-1-(2-azithromy)-7-methoxy-2,3-dimethyl-1,4-dihydroindeno [1,2-b]pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 63 mg of platinum oxide for 2.5 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. Received blignault oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 123 mg (1,06 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 16 h at room temperature, then was filtered yellowish crystals. As a result received 528 mg (76%) fumarata (S)-2- (7-methoxy-2,3-dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine (1: 0,5) so pl. 197o.

Example 36

a) cooled to -70othe solution 2,96 g (18.3 mmol) of 6-methoxy-1-indanone in 300 ml of anhydrous tetrahydrofuran under stirring was added dropwise a freshly prepared from 3,12 ml (22 mmole) of Diisopropylamine and 13.8 ml (22 mmole) of 1,6 H n-utility in hexane solution sitedisability in 40 ml of anhydrous tetrahydrofuran. Mixing p is l (20.2 mmol) of chloroacetone in 40 ml of anhydrous tetrahydrofuran. The reaction mixture was cooled for 90 min to room temperature and continued to stir for 45 min at this temperature. Then the reaction mixture was poured into 100 ml of ice, was added 100 ml of saturated sodium chloride solution and the separated organic phase. The aqueous phase is once was extracted with 300 ml of diethyl ether, the combined organic phases are once washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The obtained red oil was purified by column chromatography on silica gel (hexane/diethyl ether 3: 2). The result obtained 2.24 g (56%) of (RS)-6-methoxy-2-(2-oxopropyl)-1 - indanone as a yellow solid, which without additional recrystallization was used in subsequent reactions.

b) a Solution of 1.45 g (6,64 mmol) (RS)-6-methoxy-2-(2-oxopropyl)-1 - indanone and 60 mg p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.0 g (26.6 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 90 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified, palocci-2-methyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a yellow solid with so pl. 110o.

in) cooled to 0oa solution of 0.8 g (3.1 mmole) of (R)-1-(7-methoxy - 2 - methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 1.73 ml (12.4 mmol) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise to 0.48 ml (6.2 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 60 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 25 ml of anhydrous dimethylformamide was treated with 0.40 g (6.2 mmol) of sodium azide and the reaction mixture was heated for 16 h under stirring to 60o. After cooling the solution was poured into 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. Receive what they get of 0.44 g (50%) of (S)-1-(2-azithromy)-7-methoxy-2 - methyl-1,4-dihydroindeno[1,2-b] pyrrole as a pale yellow oil.

g) of 0.44 g (of 1.56 mmole) of (S)-1-(2-azithromy)-7-methoxy-2 - methyl-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 35 ml of anhydrous ethanol, was first made in the presence of 45 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. Received blignault oil was dissolved in 35 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 90 mg (0,78 mmole) of fumaric acid in 7 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered yellowish crystals. In the received 414 mg (84%) fumarata (S)-2-(7-methoxy-2-methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine (1:0,5) so pl. 199o.

Example 37

a) a Solution of 14.0 g (84 mmole) of 4-chloro-1-indanone of 17.3 ml of 0.20 mol) of 3-butene-2-ol and 140 mg of p-toluenesulfonic acid in 140 ml of 2,2 - dimethoxypropane for 64 h boiled under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 6:1). The result obtained 15.2 g (81%) of (RS)-2-(2-butene-1-yl)-4-chloro-1-indanone as a yellow oil.

C) a Solution of 2.08 g (10.0 mmol) of (RS)-2-(2-oxoethyl)-4-chloro-1 - indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified is 1-(5-chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.47 g (5.93 mmol) of (RS)-1-(5-chloro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3.3 ml (23.7 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 0.92 ml (11.9 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 50 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated of 0.77 g (11.9 mmol) of sodium azide and the reaction mixture was heated for 17 h under stirring to 60o. After cooling the solution was poured into 80 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil cleansing is)-1- (2-azithromy)-5-chloro-1,4-dihydroindeno [1,2-b] pyrrole as a pale yellow oil.

d) 1.0 g (3,66 mmole) of (RS)-1-(2-azithromy)-5-chloro-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 100 mg of platinum oxide for 5 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 80 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 212 mg (1,83 mmole) of fumaric acid in 16 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. The result has been of 1.05 g (94%) fumarata (RS)-2-(5-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 182o.

Example 38

a) a Solution of 1.8 g (of 8.25 mmol) (RS)-6-methoxy-2-(2-oxopropyl)-1-indanone and 70 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution 2,48 g (33 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 90 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been the VA, which is directly used in the subsequent reaction.

b) cooled to 0oa solution of 1.35 g (5.25 mmol) of (RS)-1-(7 - methoxy-2-methyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl) -propan-2-ol and of 2.92 ml (21,0 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise 0,81 ml (10.5 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 120 ml of dichloromethane, washed twice respectively with 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 90 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 40 ml of anhydrous dimethylformamide was treated with 0.68 g (10.5 mmol) of sodium azide and the reaction mixture under stirring was heated for 23 h to 80o. After cooling the solution was poured into 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated sodium chloride solution, dried over sulfate is ecografia on silica gel (toluene). The result has been 0,93 g (63%) of (RS)-1-(2-azithromy)-7-methoxy-2-methyl-1,4-dihydroindeno[1,2-b] pyrrole as a pale yellow oil.

in) 0,92 g (3,26 mmole) of (RS)-1-(2-azithromy)-7-methoxy-2-methyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 70 ml of anhydrous ethanol, was first made in the presence of 90 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained oil, lightly painted yellow, was dissolved in 70 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 189 mg (1,63 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered crystals, slightly colored in yellow. As a result received 800 mg (78%) fumarata (RS)-2-(7-methoxy-2-methyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) Art. pl. 187 - 188o.

Example 39

a) a Solution of 11.2 g (64.1 mol) of 6-isopropyl-1-indanone, and 13.3 ml (0,15 mol) C-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2 - dimethoxypropane boiled for 89 h under reflux in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in sakurado with 6.6 g of educt was obtained 5.6 g (38%) of (RS)-2-(2-butene-1-yl)-6-isopropyl-1-indanone as a yellow oil.

b) cooled to -70oa solution of 5.6 g (24.5 mmole) of (RS)- 2-(2-butene-1-yl)-6-isopropyl-1-indanone in 125 ml of anhydrous dichloromethane and 25 ml of anhydrous methanol under stirring missed during 50 min stream of ozone (2 g ozone/hour). Then the solution was purged for min oxygen for 10 minutes with argon. After the addition of 2.7 ml (36.8 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 60 ml of dichloromethane and, after addition of 10 ml water and 10 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 50 ml of water and neutralized with stirring, adding with a spatula sodium bicarbonate. Then add another 50 ml of water, separated phase and the aqueous phase was extracted twice respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been to 5.08 g (95%) of (RS)-2-(2-oxoethyl)-6-isopropyl-1-indanone as a yellow oil.

C) a Solution of 2.16 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-isopropyl-1-indanone and 80 mg of p-toluenesulfonic acid in 60 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 and boil for 45 min, moreover, the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result was obtained 1.4 g (55%) of (RS)-1-(7-isopropyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.38 g (5.4 mmol) of (RS)-1-(7 - isopropyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and a 3.01 ml (21.6 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise from 0.84 ml (10.8 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, and treated with 0.7 g (10.8 mmol) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 70 ml of water and dwai demo once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 1,08 g (72%) of (RS)-1-(2-azithromy)-7-isopropyl - 1,4-dihydroindeno [1,2-b] pyrrole in the form of oil, lightly colored in yellow.

d) 1.06 g (of 3.78 mmole) of (RS)-1-(2-azithromy)-7-isopropyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 110 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 80 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 219 mg (1.89 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered white crystals. As a result received 918 mg (78%) fumarata (RS)-2-(7 - isopropyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 203o.

Example 40

a) a Solution of 2.16 g (10 mmol) of (RS)-2- (2-oxoethyl)-6-isopropyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 myopathic for 45 min, moreover, the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been 1.78 g (70%) of (R)-1-(7-isopropyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

b) cooled to 0oa solution of 1.78 g (6,97 mmol) of (R)-1-(7 - isopropyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 3,86 ml (27.9 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise at 1.08 ml (13.9 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 70 ml of dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated of 0.91 g (13.9 mmol) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o. After cooling the solution was poured into 150 ml of water and two once respectively 100 ml of water and 100 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result obtained 1.12 g (57%) of (S)-1-(2 - azithromy)-7-isopropyl-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

in) 1.12 g (3,99 mmole) of (S)-1-(2-azithromy)-7-isopropyl-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 112 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 232 mg (2.0 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 5 h at room temperature, then was filtered white crystals. As a result received 371 mg (29%) fumarata (S)-2-(7-isopropyl - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,57) so pl. 179 - 181o.

Example 41

a) a Solution of 11.0 g (58,0 mmol) of 6-tert.-butyl-1-indanone, 12.5 ml (145 mmol) of Z-butene-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2 - dimethoxypropane boiled under reflux for 41 hours vodoohda was purified by column chromatography on silica gel (hexane/diethyl ether 6:1). The result has been to 7.35 g (53%) of (RS)-2-(2-butene-1-yl)-6-tert.-butyl-1 - indanone as a yellow oil.

b) cooled to -70oa solution of 7.35 g (30.5 mmol) of (RS)-2-(2 - butene-1-yl)-6-tert. -butyl-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed during 35 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After addition to 3.36 ml (45.8 mmol) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 100 ml of dichloromethane and, after addition of 15 ml water and 15 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, the phases were separated and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 6,44 g (92%) of (RS)-2-(2-oxoethyl)-6-tert.-butyl-1-indanone as a yellow oil.

C) a Solution of 2.3 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-tert.-butyl-1-indanone and 80 m the h was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been to 1.9 g (70%) of (R)-1-(7-tert.-butyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 1.9 g (7.05 mmol) of (R)-1-(7-tert.-butyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 3.9 ml (28,2 mmol) of triethylamine in 55 ml of dichloromethane under stirring was added dropwise 1.1 ml (14.1 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The resulting brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated 0,83 g (12.6 mmol) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o

d) of 0.82 g (2.8 mmole) of (S)-1-(2-azithromy)-7-tert.-butyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 80 mg of platinum oxide for 2 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 50 ml of anhydrous dietilovogo ether, filtered and with stirring, treated with a solution of 163 mg (1.4 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 15 h at room temperature, then was filtered crystals are pink. The result was obtained 0.33 g (36%) fumarata (S)-2-(7-tert.-butyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1 - methylethylamine (1:0,5) so pl. 188-190o.

Example 42

a) a Solution 9,73 g (45 mmol) of 5'-methoxy-2',3'-dihydroxypropane boiled under reflux for 90 h in the water separator, filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuo, then purified by column chromatography on silica gel (hexane/ethyl acetate 7:1). As a result, along with 4.0 g of educt received 6,24 g (51%) of (RS)-2'-(2-butene-1-yl)-5'-methoxy-2', 3'- dihydrospiro[cyclopentane-1,1'-[1H]inden]-3'-it is in the form of a yellow oil.

b) cooled to -70oa solution of 6.2 g (22.9 mmole) of (RS)-2'-(2-butene-1-yl)-5'-methoxy-2', 3'-dihydrospiro[cyclopentane-1,1'- [1H]inden]-3'-she's in 80 ml of anhydrous dichloromethane and 20 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (2.5 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 2,52 ml (34.4 mmole) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 100 ml of dichloromethane and, after addition of 15 ml water and 15 ml triperoxonane acid was stirred for 2.5 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, separated phase and the aqueous phase was twice extracted, respectively, is the Aquum. As a result, received a grade of 5.74 g (97%) of (RS)-2'-(2-oxoethyl)-5'-methoxy-2', 3'- dihydrospiro[cyclopentane-1,G-[1H]inden]-3'-it is in the form of a yellowish oil.

C) a Solution of 2.58 g (10 mmol) (RS)-2'-(2-oxoethyl)-5'-methoxy - 2',3'-dihydrospiro[cyclopentane-1, G-[1H] inden]-3'-she and 80 mg of p - toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:1). The result obtained 1.98 g (67%) of (R)-1-[7'-methoxy-1', 4'-dihydrospiro[cyclopentane-1,4'-indeno [1,2 - b]pyrrole]-1'-yl]propan-2-ol as a yellow oil.

g) cooled to 0oa solution of 1.95 g (6.6 mmol) of (R)-1-[7'- methoxy-1',4'-dihydrospiro[cyclopentane-1,4'-indeno [1,2-b]pyrrol-1'-yl] propan-2-ol and the 3.65 ml (26.2 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 1.02 ml (13.1 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice was songtexttgirl with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 50 ml of anhydrous dimethylformamide, treated 0,86 g (13.2 mmol) of sodium azide and the reaction mixture under stirring was heated for 5 h to 70o. After cooling the solution was poured into 70 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 80 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). The result obtained 1.45 g (68%) of (S)- 1'-(2-azithromy)-7'-methoxy-1',4'-dihydrospiro[cyclopentane] -1,4' -indeno [1,2-b] pyrrole in the form of a yellowish oil.

d) 1.45 g (4.5 mmole) of (S)-1'-(2-azithromy)-7'-methoxy-1',4'- dihydrospiro[cyclopentane]-1,4'-indeno[1,2-b]pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 145 mg of platinum oxide for 14 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. Poluchennaya solution of 522 mg (4.5 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 5 h at room temperature, then was filtered white crystals. The result has been 1.47 g (79%) fumarata (S)-1-methyl-2-(7'-methoxy-1', 4'- dihydrospiro[cyclopentane-1,4'- indeno[1,2-b]pyrrole]-1-yl)-ethylamine (1:1) with so pl. 183 - 185o.

Example 43

a) a Solution of 25.0 g (116 mmol) 5'-methyl-2',3'- dihydrospiro[cyclohexane - 1,1'-[1H] inden] -3'-she, 24,1 ml (280 mmol) of Z-butene-2-ol and 250 mg of p-toluenesulfonic acid in 250 ml of 2,2-dimethoxypropane boiled under reflux for 88 hours in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 6: 1). As a result, along with 8.4 g of educt received an 18.4 g (59%) of (RS)-2'-(2-butene-1-yl)-5'-methyl-2', 3'-dihydrospiro[cyclohexane - 1,1'-[1H]inden]-3'-it is in the form of a yellow oil.

b) cooled to -70oa solution of 18.4 g (68.5 mmol) of (RS)-2'-(2-butene-1-yl)-5'-methyl-2',3'-dihydrospiro[cyclohexane-1,1'-[1H]inden]-3'-she's in 300 ml of anhydrous dichloromethane and 60 ml of anhydrous methanol under stirring passed within 75 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After longprivate in vacuum, the residue was treated with 200 ml of dichloromethane and, after addition of 30 ml water and 30 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 200 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result obtained 17.0 g (97%) of (RS)-2'-(2-oxoethyl-5'-methyl-2',3'-dihydrospiro [cyclohexane-1,1'-[1H]inden] -3'-it is in the form of a yellow oil.

C) a Solution of 2.56 g (10 mmol) (RS)-2'-(2-oxoethyl)-5'-metil-2',3'- dihydrospiro[cyclohexane-1,1'-[1H] inden] -3'-she and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 2:3). The result has been of 2.45 g (83%) of (R)-1-[7'-methyl-1', 4'-dihydrospiro[cyclohexane-1,Astor of 2.45 g (8.3 mmol) of (R)-1- [7'-methyl-G, 4'-dihydrospiro[cyclohexane-1,4'-indeno[1,2-b]pyrrole] -1'-yl]-propan-2-ol and 4.57 ml (33,2 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 1.3 ml (16.6 mmol) of methanesulfonamide and continued to stir for 2.5 h at this temperature. Then the reaction mixture was diluted in 100 ml of dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained yellow oil was dissolved in 75 ml of anhydrous dimethylformamide, and treated with 1.08 g (16.6 mmol) of sodium azide and the reaction mixture was heated with stirring for 16 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 90 ml of water and 90 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on with logician] -1,4'-indeno[1,2-b] pyrrole in the form of oil, lightly colored red.

d) of 1.76 g (5,49 mmol) (S)-1'-(2-azithromy)-7'-methyl-1',4'- dihydrospiro[cyclohexane] -1,4'-indeno[1,2-b] pyrrole dissolved in 100 ml of anhydrous ethanol, was first made in the presence of 170 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The resulting brownish oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 637 mg (5,49 mmol) of fumaric acid in 10 ml of methanol. Then was stirred for 22 h at room temperature, then was filtered white crystals. The result was obtained 1.7 g (76%) fumarata (S)-1-methyl-2-(7'-methyl-1', 4'-dihydrospiro[cyclohexane-1,4'- indeno[1,2-b]pyrrole]-1-yl)-ethylamine (1:1) with so pl. 195 - 196o.

Example 44

a) a Solution of 17.0 g (84,8 mmole) of 5'-methyl-2',3'-dihydrospiro [cyclopentane-1,1'-[1H] inden] -3'-she, of 17.5 ml (204 mmole) of Z - butene-2-ol and 170 mg of p-toluenesulfonic acid in 170 ml of 2,2-dimethoxypropane boiled under reflux for 71 hours in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on Sealy is,3'-dihydrospiro [cyclopentane-1,1'-[1H]inden]-3'-it is in the form of a yellow oil.

b) cooled to -70oa solution of 12.7 g (50.1 mmol) of (RS)-2'- (2 - butene-1-yl)-5'-methyl-2',3'-dihydrospiro[cyclopentane-1,G-[1H] inden]-3'-it in 250 ml of anhydrous dichloromethane and 50 ml of anhydrous methanol was passed with stirring for 60 minutes a stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 5,54 ml (75.5 mmol) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 160 ml of dichloromethane and, after addition of 15 ml water and 15 ml triperoxonane acid was stirred for 2.5 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result obtained 12 g (99%) of (RS)-2'-(2-oxoethyl)-5'-methyl-2', 3'- dihydrospiro[cyclopentane-1,1'-[1H]inden]-3'-it is in the form of oil, lightly colored red.

C) the Solution to 2.42 g (10 mmol) (RS)-2'-(2-oxoethyl)-5'-methyl-2',3'-dihydrospiro[CIE. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (R)-1 - amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of the Reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 3: 2). The result has been to 2.06 g (73%) of (R)-1-[7'-methyl-1',4'-dihydrospiro[cyclopentane-1,4'-indeno [1,2-b] pyrrole] -1'-yl]-propan-2-ol as a red oil.

g) cooled to 0oa solution of 2.06 g (to 7.32 mmol) of (R)-1-[7'-methyl-1', 4'-dihydrospiro[cyclopentane-1,4'-indeno[1,2-b] pyrrole]-1'-yl]-propan-2-ol and a 4.03 ml (14.6 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise to 1.15 ml (14.6 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 75 ml of be is eshiwani for 5 h to 70o. After cooling the solution was poured into 100 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). The result has been of 1.34 g (60%) (S)-1'- (2-azithromy)-7'-methyl-1,4'-dihydrospiro[cyclopentane] -1,4'- indeno[1,2-b]pyrrole in the form of oil, lightly colored red.

d) of 1.34 g (4,37 mmole) of (S)-1'-(2-azithromy)-7'-methyl-1',4'- dihydrospiro[cyclopentane]-1,4'-indeno[1,2-b]pyrrole dissolved in 75 ml of anhydrous ethanol, was first made in the presence of 135 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 80 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 507 mg (4,37 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for hours at room temperature and was filtered white crystals. The result has been to 1.23 g (71%) fumarata (S)-tx2">

Example 45

a) a Solution of 1.05 g (4,13 mmole) of (RS)-1-(2-azithromy)-7-hydroxy-1,4-dihydroindeno[1,2-b]pyrrol and 0.77 ml (compared to 8.26 mmol) of Isopropylamine, 1,14 g (compared to 8.26 mmol) of potassium carbonate in 30 ml of N,N-dimethylformamide was heated for 48 h before 50o. After cooling the solution was poured into 150 ml of water and was extracted twice respectively in portions of 150 ml of ethyl acetate. The combined organic phases are washed once with 70 ml Polynesians solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The crude product was purified by column chromatography on silica gel (toluene). The result was obtained 0.35 g (28%) of (RS)-1-(2-azithromy)-7-isopropoxy-1,4-dihydroindeno[1,2-b] pyrrole in the form of an orange oil, which was directly used in the subsequent reaction.

b) 0.35 g (1,17 mmole) of (RS)-1-(2-azithromy)-7-isopropoxy-1,4 - dihydroindeno[1,2-b] pyrrole dissolved in 40 ml of anhydrous ethanol, was first made in the presence of 40 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 70 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 68 mg (0, which it was filtered white crystals. The result was obtained 0.22 mg (57%) fumarata (RS)-2-(7-isopropoxy-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 192o.

Example 46

a) a Solution of 8.0 g (54 mmole) of 6-hydroxy-1-indanone, 6.3 ml (59.4 mmol) of cyclopentylamine, and 16.4 g (119 mmol) of potassium carbonate and 10 ml of N,N-dimethylformamide in 100 ml of acetone was heated for 35 h to 75o. After cooling the solution was poured into 150 ml of water and was extracted twice respectively in portions of 200 ml of ethyl acetate. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The crude product was purified by column chromatography on silica gel (hexane/ethyl acetate 3: 1). The result has been to 9.45 g (81%) 6 cyclopentane-1-indanone in the form of an orange oil, which was directly used in the subsequent reaction.

b) a Solution of 9.45 g (43,7 mmole) 6-cyclopentane-1-indanone, 9,0 ml (105 mmol) of Z-butene-2-ol and 100 mg of p-toluenesulfonic acid in 100 ml of 2,2-dimethoxypropane boiled under reflux for 63 hours in a water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture conc the Il 6:1). The result has been to 8.1 g (69%) of (RS)-2-(2-butene-1-yl)-6-cyclopentyloxy-1-indanone as a yellow oil.

C) After cooled to -70oa solution of 8.1 g (29.9 mmol) of (RS)-2-(2-butene-1-yl)-6-cyclopentyloxy-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol was passed with stirring for 60 minutes a stream of ozone (1.5 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 3,29 ml (44,9 mmole) of dimethyl sulfide was stirred for 21 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 75 ml of dichloromethane and, after addition of 12.5 ml of water and 12.5 ml triperoxonane acid was stirred for 5 h at room temperature. Then the mixture was poured into 150 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 5,63 g (73%) of (RS)-2-(2-oxoethyl)-6 - cyclopentyloxy-1-indanone in the form of an orange oil.

g) a Solution of 2.58 g (10 mmol) of (RS)-2-(2-oxoethyl)-6-Cyclops is the first solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7: 3). The result obtained 1.44 g (48%) of (RS)-1-(7-cyclopentane-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a pale yellow oil.

d) cooled to 0oa solution of 1.44 g (4.8 mmole) of (RS)-1-(7 - cyclopentane-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 2.66 ml (19.3 mmol) of triethylamine in 55 ml of dichloromethane under stirring was added dropwise 0.75 ml (9.6 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 30 ml of anhydrous dimethylformamide, treated of 0.62 g (9.6 mmol) of sodium azide and the reaction mixture was heated with stirring for 16 h to 60o

e) 1.27 g (3,93 mmole) of (RS)-1-(2-azithromy)-7-cyclopentane-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 75 ml of anhydrous ethanol, was first made in the presence of 125 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained oil, lightly colored red, was dissolved in 80 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 198 mg (1.7 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered crystals, slightly colored in pink. The result obtained 926 mg (80%) fumarata (RS)-2-(7-cyclopentane - 1,4 - dihydr the 0oa solution of 12.0 g (81 mmol) of 6-hydroxy-1-indanone and 45,2 ml (162 mmole) of triethylamine in 350 ml of dichloromethane under stirring was added dropwise of 12.6 ml (162 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml dichloromethane, washed twice respectively in portions of 150 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 100 ml dichloromethane. The combined organic phases are washed with 200 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The result has been to 18.3 g (99%) 6-mesilate-1-indanone as a brown solid, which was directly used in the subsequent reaction.

b) a Solution of 18.5 g (of $ 80.9 mmol) 6-mesilate-1-indanone, and 16.7 ml (194 mmole) of Z-butene-2-ol and 300 mg of p-toluenesulfonic acid in 400 ml of 2,2 - dimethoxypropane boiled under reflux for 46 h in the water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). As a result, along with 8,31 g of educt was obtained 11.3 g is actor 11.3 g (40.3 mmol) of (RS)-2-(2-butene-2-yl)-6-mesilate-1-indanone in 300 ml of anhydrous dichloromethane and 60 ml of anhydrous methanol under stirring missed during 55 min stream of ozone (2 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 4,51 ml (61.5 mmole) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 250 ml of dichloromethane and, after addition of 25 ml water and 25 ml triperoxonane acid was stirred for 4 h at room temperature. Then the mixture was poured into 200 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then add another 50 ml of water, separated phase and the aqueous phase was extracted twice respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result has been 9,38 g (85%) of (RS)-2-(2-oxoethyl)-6-mesilate-1-indanone in the form of a light-brown solid with so pl. 85 - 87o.

g) Solution 2,31 g (8,59 mmol) (RS)-2-(2-oxoethyl)-6 - mesilate-1-indanone and 110 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.58 g (34.4 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of rustikale (ethyl acetate/hexane 2:3). The result has been 0.74 g (28%) of (RS)-1-(7-mesilate-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a solid substance of a brownish color, which is directly used in the subsequent reaction.

d) cooled to 0othe solution to 0.72 g (of 2.38 mmole) of (RS)-1-(7 - mesilate-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol and of 1.33 ml (at 9.53 mmol) of triethylamine in 30 ml of dichloromethane under stirring was added dropwise and 0.37 ml (4,77 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. Received green oil was dissolved in 30 ml of anhydrous dimethylformamide, treated of 0.62 g (of 4.77 mmole) of sodium azide and the reaction mixture under stirring was heated for 16 h to 60o. After cooling the solution was poured into 70 ml of water and was extracted twice respectively portions 70 ml of ethyl acetate. United organsie over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (ethyl acetate/hexane 1: 4). The result was obtained 0.68 g (86%) of (RS)-1-(2-azithromy)-7-mesilate-1,4-dihydroindeno [1,2-b] pyrrole in the form of a slightly yellow color solid, which was directly used in the subsequent reaction.

e) 0.66 g (2.0 mmole) of (RS)-1-(2-azithromy)-7-mesilate-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 66 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The resulting brownish oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 116 mg (1.0 mmol) of fumaric acid in 10 ml of methanol. Then was stirred for 17 h at room temperature, then was filtered crystals, slightly colored in pink. The result obtained 400 mg (55%) fumarata (RS)-2-(7-mesilate-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1: 0,5) so pl. 201o.

Example 48

a) cooled to -70othe solution 3,24 g (20.0 mmol) of 5-methoxy-1-indanone in 350 ml of anhydrous tetrahydrofuran at prigotovlennyi of of 4.25 ml (30.0 mmol) of Diisopropylamine and 18.7 ml (30.0 mmol) of 1.6 H n-utility in hexane. Then continued to stir for 45 min at this temperature, and then for 15 min was added dropwise a solution of 1.6 ml (20.0 mmol) of chloroacetone in 60 ml of anhydrous tetrahydrofuran. The reaction mixture for 100 min, allowed to cool to room temperature and continued to stir for 45 min at this temperature. Then the reaction mixture was poured into 150 ml of ice was added 150 ml of a saturated solution of sodium chloride and separated the organic phase. The aqueous phase is once was extracted with 400 ml of diethyl ether, the combined organic phases are once washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The obtained red oil was purified by column chromatography on silica gel (hexane/diethyl ether 3:7). The result has been 1,67 g crude product, which was recrystallized from diethyl ether/hexane. After crystallization got to 1.21 g (56%) of (RS)-5-methoxy-2-(2-oxopropyl)-1-indanone as a yellowish solid substance, so pl. 73o.

b) a Solution of 1.2 g (5.5 mmol) of (RS)-5-methoxy-2-(2-oxopropyl)-1-indanone and 60 mg p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In boiling rest the same time continued to boil for 90 min, moreover, the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been 1,17 g (82%) of (RS)-1-(6-methoxy-2 - methyl-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol as a yellow solid, which without further recrystallization was used in subsequent reactions.

in) cooled to 0oa solution of 1.16 g (4,51 mmole) of (RS)-1-(6 - methoxy-2-methyl-1,4-dihydroindeno[1,2-b] -pyrrol-1-yl)-propan-2-ol and 2.5 ml (18.0 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 0.7 ml (9.0 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 100 ml dichloromethane, washed twice respectively in portions of 60 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 60 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.58 g (9.0 mmol) of sodium azide and the reaction mixture was perigiali respectively 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 0,86 g (68%) of (RS)-1-(2-azithromy)-6-methoxy - 2 - methyl-1,4-dihydroindeno[1,2-b] pyrrole as a yellow oil,

g) of 0.85 g (a 3.01 mmole) of (RS)-1-(2-azithromy)-6-methoxy-2 - methyl-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 85 mg of platinum oxide for 17 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained yellowish oil was dissolved in 70 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 175 mg (1,51 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 19 h at room temperature and was filtered whitish crystals. As a result received 779 mg (82%) fumarata (RS)-2-(6-methoxy - 2-methyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1: 0,5) so pl. 218o.

Example 49

a) a Solution of 12.3 g (61,2 mmole) of 5,6-dichloro-1-indanone of 12.6 ml (0,15 mol) C-Bute in the water separator, filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). As a result, along with 4.3 g of educt was obtained 10.8 g (69%) of (RS)-2-(2-butene-1-yl) -5,6-dichloro-1-indanone as a yellow oil.

b) cooled to -70oa solution of 10.8 g (42,4 mmole) of (RS)-2-(2 - butene-1-yl)-5,6-dichloro-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol under stirring missed for 45 min stream of ozone (3.5 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 4.66 ml (63,6 mmole) of dimethyl sulfide was stirred for 3 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 150 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, separated phase and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over soul from hexane/ethyl acetate. After crystallization got to 7.59 g (73%) of (RS)-2-(2-oxoethyl)-5,6-dichloro-1-indanone in a solid yellow color with so pl. 93-96o.

C) a Solution of 2.0 g (8.23 mmol) of (RS)-2-(2-oxoethyl)-5,6-dichloro-1-indanone and 70 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2,47 g (32,9 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 4:1). The result has been to 0.62 g (27%) of (RS)-1-(6,7-dichloro-1,4 - dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol as a brown oil.

g) cooled to 0oa solution of 0.6 g (2.12 mmole) of (RS)-1-(6,7-dichloro - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 1.18 ml (8.5 mmol) of triethylamine in 30 ml of dichloromethane under stirring was added dropwise 0.33 ml (4.25 mmole) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 50 ml dichloromethane, washed twice respectively portions 70 ml of a saturated solution of bicarbonate Natrii washed with 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, treated 275 mg (4,24 mmole) of sodium azide and the reaction mixture under stirring was heated for 17 h to 60o. After cooling the solution was poured into 60 ml of water and was extracted three times respectively portions 90 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.45 g (69%) of (RS)-1-(2-azithromy)-6,7 - dichloro-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

d) of 0.44 g (1,43 mmole) of (RS)-1-(2-azithromy)-6,7-dichloro-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 45 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 30 ml of anhydrous dietilovogo ether, filtered and with stirring, treated with a solution of 83 mg (0.72 mmole) of fumaric and white crystals. As a result received 395 mg (81%) fumarata (RS)-2-(6,7 - dichloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (12:0,5) so pl. 203o.

Example 50

a) a Solution of 13.0 g (89 mmol) of 4-methyl-1-indanone, and 19.2 ml (to 0.22 mole) of 3-butene-2-ol and 170 mg of p-toluenesulfonic acid in 170 ml of 2,2 - dimethoxypropane boiled under reflux for 46 h in the water separator filled with molecular sieve (0.4 nm, granules 2 mm). Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result obtained 12.0 g (67%) of (RS)-2-(2-butene-1-yl)-4-methyl-1-indanone as a yellow oil.

b) cooled to -70oa solution of 12.0 g (60 mmol) of (RS)-2-(2 - butene-1-yl)-4-methyl-1-indanone in 220 ml of anhydrous dichloromethane and 45 ml of anhydrous methanol under stirring missed over 90 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 6.6 ml (90 mmol) of dimethyl sulfide was stirred for 15 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 160 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 2 h at room the El, sodium bicarbonate. After this was added 50 ml of water, are of the same phase and aqueous phase. twice were extracted respectively in portions of 200 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result was obtained 10.6 g (94%) of (RS)-2-(2-oxoethyl)-4-methyl-1-indanone in the form of oil is pale yellow in color.

C) a Solution of 1.9 g (10.0 mmol) of (RS)-2- (2-oxoethyl)-4-methyl-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 45 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been to 0.63 g (28%) of (RS)-1-(5-methyl-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-propan-2-ol as a white solid, which was directly used in the subsequent reaction.

g) cooled to 0othe solution to 0.63 g (2.8 mmole) of (RS)-1-(5-methyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 1.6 ml (11.2 mmol) of triethylamine in 25 ml of dichloromethane under stirring domainator. Then the reaction mixture was diluted with 50 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained solid green color was dissolved in 30 ml of anhydrous dimethylformamide, and treated with 0.36 g (5.6 mmol) of sodium azide and the reaction mixture was heated with stirring for 16 h to 60o. After cooling the solution was poured into 80 ml of water and was extracted three times respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70. ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 0,69 g (98%) of (RS)-1-(2-azithromy)-5-methyl-1,4-dihydroindeno [1,2-b] pyrrole in the form of a yellowish oil.

d) 0,69 g (2.7 mmole) of (RS)-1-(2-azithromy)-5-methyl-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 30 ml without the Torah, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 80 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 157 mg (of 1.35 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. The result obtained 0.34 g (44%) fumarata (RS)-2-(5-methyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 214o.

Example 51

a) Through cooled to -70oa solution of 10.1 g (50 mmol) of (RS)-2-(2-butene-1-yl)-4-chromanone in 100 ml of anhydrous dichloromethane and 300 ml of anhydrous methanol under stirring missed during 55 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and within 15 minutes was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue together with 5,62 g (55 mmol) of N - acetylethylenediamine was dissolved in 100 ml of concentrated acetic acid and boiled for 45 min under reflux. Then the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (ethyl acetate). The result was obtained 5.7 g (45%) of N-[2-(1,4-Digi the second recrystallization was used in subsequent reactions.

b) a Mixture of 2.5 g (9.7 mmol) of N-[2-(l, 4-dihydro-[1]benzopyrano[4,3-b] pyrrol-1-yl)-ethyl] -acetamide", she 3.28 g (58 mmol) of potassium hydroxide, 20 ml of water and 40 ml of ethylene glycol was heated with stirring for 23 h to 110o. After cooling, the reaction mixture was poured into 100 ml saturated sodium chloride solution and was extracted three times respectively in portions of 200 ml of ethyl acetate. The organic phase once washed with 200 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica gel (dichloromethane/methanol/ammonia 200:10:1). The resulting oil was dissolved in 110 ml of anhydrous diethyl ether, filtered and treated with a solution of 436 mg (3.8 mmole) of fumaric acid in 20 ml of anhydrous methanol. Then was stirred for 18 h at room temperature, then was filtered by suction white crystals. As a result received 812 mg (31%) fumarata 2-(1,4-dihydro-[1]benzopyrano[4,3-b]pyrrol-1-yl)-ethylamine (1:0,5) so pl. 180o.

Example 52

a) a Solution of 1.9 g (10.0 mmol) of (RS)-2-(2-oxoethyl)-4-chromanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added p is for 35 min, moreover, the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2: 3). The result has been to 1.9 g (83%) of (R)-1-(1,4-dihydro-[1] benzopyrano[4,3-b] pyrrol-1-yl)-propan-2-ol as a yellow oil.

b) cooled to 0oa solution of 1.88 g (8.2 mmol) of (R)-1-(1,4 - dihydro-[1] benzopyrano[4,3-b] pyrrol-1-yl)-propan-2-ol and 4.57 ml (32,8 mmole) of triethylamine in 50 ml of anhydrous dichloromethane under stirring was added dropwise to 1.27 ml (16.4 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 280 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases are washed with 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained solid brown was dissolved in 50 ml of anhydrous dimethylformamide, and treated with 1.0 g (15.2 mmol) of sodium azide and the reaction mixture was heated with stirring for 18 h to 60o. After cooling rest what's the organic phase was washed once each respectively 100 ml of water and 100 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil In the received 1,67 g (80%) of (S)-1-(2-azithromy)-1,4 - dihydro-[1]benzopyrano[4,3-b]pyrrole as a colorless oil.

in) of 1.65 g (6.5 mmol) of (S)-1-(2-azithromy)-1,4-dihydro- [1]benzopyrano[4,3-b] pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 170 mg of platinum oxide for 4 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. Thus obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 309 mg (or 2.67 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. The result obtained 1.35 g (73%) fumarata (S)-1-(1,4 - dihydro-[1] benzopyrano[4,3-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 194 - 195o.

Example 53

a) a Solution of 25 grams (0.15 mole) of 5-chloro-1-indanone, 31 ml of 0.36 mole) of 3 - butene-2-ol and 250 mg of p-toluenesulfonic acid in 31 ml of 2,2 - dimethoxypropane and 250 ml of anhydrous toluene was heated for 17 h under reflux. Then the reaction mixture was concentrated in vacuum and purified pore-butene-1-yl)-5-chloro-1-indanone as a yellow oil.

b) cooled to -70oa solution of 11.9 g (53,9 mmole) of (RS)-2-(2-.butene-1-yl)-5-chloro-1-indanone in 200 ml of anhydrous dichloromethane and 100 ml of anhydrous methanol was passed with stirring for 60 minutes a stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 5.9 ml (for 80.9 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 50 ml of dichloromethane and, after addition of 12 ml of water and 12 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was extracted with portions respectively 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from ethyl acetate/hexane. The result has been 8,98 g (80%) of (RS)-2-(2-oxoethyl)-6-chloro-1-indanone as a white solid with so pl. 66o.

C) a Solution of 2 g (9.6 mmol) of (RS)-2-(2-oxoethyl)-5-chloro-1-indanone and 100 mg p-toluenesulfonic acid in 90 PR 2,88 g (38.3 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 30 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). The result has been to 1.9 g (80%) of (RS)-1-(6-chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

g) cooled to 0oa solution of 1.9 g (7.7 mmol) of (RS)-1-(6-chloro-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 4.3 ml (30.6 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise 1.2 ml (15.3 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml dichloromethane, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, and treated with 1.0 g (15.3 mmol) of sodium azide and the reaction mixture when Perelli respectively portions 140 ml of diethyl ether and once with 140 ml of ethyl acetate. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.8 g (38%) of (RS)-1- (2-azithromy)-6-chloro-1,4-dihydroindeno [1,2-b] pyrrole in the form of a yellowish oil.

d) 0.8 g (2.9 mmole) of (RS)-1-(2-azithromy)-6-chloro-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 80 ml of anhydrous ethanol, was first made in the presence of 80 mg of platinum oxide for 3 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 150 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 170 mg (1,46 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 4 h at room temperature, then was filtered white crystals. As a result received 780 mg (87%) fumarata (RS)-2-(6-chloro-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 212o.

Example 54

a) a Solution of 11.9 g (66,7 mmol) 7-methoxy-4-chromanone for 13.8 ml (0,16 mol) C-butene-2-ol and 120 mg of p-that is dildocam. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). The result obtained 6.3 g (41%) of (RS)- 2-(2 butene-1-yl)-7-methoxy-4-chromanone in the form of a yellow oil.

b) cooled to -70oa solution of 6.25 g (26.9 mmol) of (RS)-2-(2-butene-1-yl)-7-methoxy-4-chromanone in 90 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol was passed with stirring for 1 h the flow of the ozone

(3 g ozone/hour). Then the solution was purged for 5 min with oxygen for 15 min with argon. After addition of 3 ml (40.5 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. Then the reaction mixture was evaporated in vacuo, the residue was treated with 60 ml of dichloromethane and, after addition of 15 ml water and 15 ml triperoxonane acid was stirred for 3 h at room temperature. Then the reaction mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then was added 70 ml of water, separated phase and the aqueous phase was twice extracted with respectively 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. In financial p is Olga) (RS)-2-(2-oxoethyl)-7-methoxy-4 - chromanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.25 g (43,2 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2:3). The result has been 1,95 g (70%) of (RS)-1-(1,4-dihydro-8 - methoxy-[1]benzopyrano[4,3-b]pyrrol-1-yl)-propan-2-ol in the form of a brown oil.

g) cooled to 0oa solution of 1.92 g (7.4 mmol) of (RS)-1-(1,4-dihydro-8-methoxy- [1]benzopyrano[4,3-b]pyrrol-1-yl)-propan-2-ol and 4.13 ml (up 29.6 mmol) of triethylamine in 50 ml of anhydrous dichloromethane under stirring was added dropwise to 1.15 ml (14.8 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 280 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases are washed with 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil rastormazhivanie was heated for 18 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 1,58 g (75%) of (RS)-1-(2-azithromy)-1,4-dihydro-8-methoxy-[1] benzopyrano [4,3-b] pyrrole as a colorless oil.

d) of 1.57 g (5.5 mmol) of (RS)-1-(2-azithromy)-1,4-dihydro-8-methoxy-[1] benzopyrano [4,3-b] pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 160 mg of platinum oxide for 17 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 281 mg (of 2.45 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. As a result received 1.42 g (86%) fumarata (RS)-1-(1,4 - dihydro-[1] benzopyrano[4,3-b]pyrrol-1-yl) - Rev. and 80 ml (0,92 mole) of 3-butene-2-ol, 132 ml (1,08 mole) of 2,2-dimethoxypropane and 600 mg of p - toluenesulfonic acid in 500 ml of toluene was heated to boiling. The resulting mixture of methanol/acetone drove away, and then the reaction solution was kept boiling for 48 h under reflux. After cooling, the solution was evaporated in vacuum. After purification on silica gel (hexane/diethyl ether 5:1) received 19,2 g (31%) of (RS)-2-(2-butene-1-yl)-5-methoxy-1-indanone in the form of oil is light yellow in color.

b) cooled to -70oa solution of 19.2 g (89 mmol) of (RS)-2-(2-butene-1-yl)-5-methoxy-1-indanone in 600 ml of anhydrous methanol under stirring missed within 85 min ozone (3 g ozone/hour). Then the solution was purged with oxygen, after which the cold solution was added 9.1 ml (0.12 moles) of dimethyl sulfide. During the night, the solution was cooled to room temperature, after which it was evaporated in vacuum. The residue was chromatographically (dichloromethane) column using adsorbed on silica gel solution of oxalic acid (600 g silica gel/100 ml of a 10% solution of oxalic acid). The result has been 14.1 g (78%) of (RS)-2-(2-oxoethyl)-5-methoxy-1-indanone as a yellow oil.

C) After cooled to -70oa solution of 13.3 g (61.5 mmole) of (RS)-2-(2-butene-1-yl for 60 minutes a stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition 6,82 ml (92,2 mmole) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 200 ml of dichloromethane and, after addition of 25 ml water and 25 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. Then was added 100 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result obtained 11.6 g (92%) of (RS)-2-(2-oxoethyl)-5 - methoxy-1-indanone as a yellow oil, which without further purification was used in subsequent reactions.

g) a Solution of 2 g (9.8 mmol) of (RS)-2-(2-oxoethyl)-5-methoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution to 2.94 g (39.2 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of rattlecage (ethyl acetate/toluene 1:1). The result was obtained 1.6 g (67%) of (RS)-1-(6-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

d) cooled to 0oa solution of 1.41 g (5.8 mmol) of (RS)-1-(6 - methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol or 3.24 ml (23,2 mmole) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 1.9 ml (11.6 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 150 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated 558 mg (8.6 mmol) of sodium azide and the reaction mixture was heated with stirring for 7 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. United organisasi over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.75 g (48%) of (RS)-1-(2-azithromy)-6-methoxy-1,4-dihydroindeno[1,2-b] pyrrole as a colorless oil.

e) 0.75 g (2.8 mmole) of (RS)-1-(2-azithromy)-6-methoxy-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 30 ml of anhydrous ethanol, was first made in the presence of 60 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 324 mg (2,79 mmole) of fumaric acid in 50 ml of methanol. Then was stirred for 16 h at room temperature, then was filtered white crystals. As a result received 530 mg (63%) fumarata (RS)-2-(6 - methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 189o.

Example 56

a) a Solution of 1.9 g (10.0 mmol) of (RS)-2-(2-oxoethyl)-4-chromanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) (8)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continue ciali by column chromatography on silica gel (ethyl acetate/toluene 2:3). As a result received 1.73 g (76%) of (S)-1-(1,4-dihydro-[1] benzopyrano[4,3-b] pyrrol-1-yl)-propan-2-ol as a yellow oil.

b) cooled to 0oa solution of 1.7 g (7.4 mmol) of (S)-1-(1,4-dihydro-[1] benzopyrano[4,3-b]pyrrol-1-yl)- propan-2-ol and 4.13 ml (29.7 mmol) of triethylamine in 50 ml of anhydrous dichloromethane under stirring was added dropwise to 1.15 ml (14.8 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases are washed with 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained solid brown was dissolved in 50 ml of anhydrous dimethylformamide was treated with 0.88 g (13.5 mmol) of sodium azide and the reaction mixture was heated with stirring for 18 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once COO is Ali solution in vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 1,49 g (79%) of (R)-1-(2-azithromy)-1,4-dihydro-[1] benzopyrano [4,3-b] pyrrole as a colorless oil.

in) 1.47 g (5.8 mmol) of (R)-1-(2-azithromy)-1,4-dihydro- [1]benzopyrano[4,3-b] pyrrole dissolved in 60 ml of anhydrous ethanol, was first made in the presence of 150 mg of platinum oxide for 18 h Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 294 mg (2,53 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 18 h at room temperature, then was filtered white crystals. The result was obtained 1.3 g (79%) fumarata (R)-1-(1,4-dihydro- [1]benzopyrano[4,3-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 194 - 195o.

Example 57

0.5 g (1.8 mmole) of N-[2-(4,5-dihydro-7-methoxy-1H-Benz[g]indol-1-yl)ethyl] -ndimethylacetamide was heated in an argon atmosphere in 21 ml of ethylene glycol/water 2:1 in the presence of 0.60 g (10.7 mmol) of potassium hydroxide for 23 h to 140o. After cooling, the reaction mixture was poured into 100 ml polycentricity once washed with a saturated solution of sodium chloride, was dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 20 ml diethyl ether and was added dropwise into a solution of 245 mg (2,11 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 1 h, then was filtered crystals are yellowish. As a result received 241 mg (38%) fumarata 2-(4,5-dihydro-7-methoxy-1H-Benz[g]indol-1-yl)-ethylamine (1:0,8) so pl. 195o.

Example 58

a) 35,25 g (0.2 mol) of 5-methoxy-1-tetralone and 61 ml of 0.8 mol) of N,N-dimethyl hydrazine was heated in an argon atmosphere for 5 h to approximately 80o. After cooling, was added 200 ml of a 10% aqueous solution of sodium chloride and was extracted several times with diethyl ether. Then was dried over sodium sulfate, filtered and evaporated. Oily residue drove using a vigreux column (10 cm). The result was obtained at 85 - 95 /0.1 mbar of 36.4 g (83%) of 5-methoxy-1-tetralone-N',N'-dimethylhydrazine in the form of a yellow oil.

b) 3.12 g (14.3 mmol) of 5-methoxy-1-tetralone-N',N'- dimethylhydrazine and 4,15 ml SLE was dissolved in argon atmosphere in 70 ml of absolute THF and cooled to -75o. Then was added dropwise to 10.7 ml of a 1.6 M solution of n-utility in hexane. Then for 1 h and was stirred at 75oafter which mediatory and was stirred for 26 hours At approximately 0owas added 20 ml of water and was extracted three times with ethyl acetate. After drying over sodium sulfate was filtered, evaporated, then the residue was chromatographically on silica gel first with toluene, then toluene/ethyl acetate 9:1. The result has been of 1.62 g (37%) of 2-(2,2-dimethoxy-1-ethyl)-5-methoxy-1-tetralone-N',N'- dimethylhydrazine in the form of butter.

in) 280 mg (0.9 mmole) of 2-(2,2-dimethoxy-1-ethyl)-5-methoxy-1 - tetralone-N', N'-dimethylhydrazine was dissolved in 12.5 ml THF, and then added 5 ml of phosphate buffer (obtained from 2 ml of 1/15 M potassium hydrogen phosphate and 3 ml of 1/15 M disodium hydrogen phosphate) and 156 mg (0.9 mmole) chloride dihydrate, copper (II). After stirring for 3.5 g at room temperature, the reaction was ended. Then was treated with 10 ml of 20% aqueous solution of ammonium chloride and 0.8 ml of concentrated ammonia. After this was extracted several times using ethyl acetate, dried over sodium sulfate, filtered and evaporated. The residue was chromatographically on silica gel first with toluene, then toluene/ethyl acetate 9: 1. As a result received 180 mg (80%) of 2-(2-oxoethyl)-5-methoxy-1-tetralone in the form of a yellowish oil (Rf=0.31, silica gel (toluene/ethyl acetate 9:1)).

g) 1 is adalnikam in the atmosphere of argon in 4 ml of acetic acid for 1.5 hours The solvent was removed in vacuo, the residue was dissolved in 25 ml of water and was extracted several times with dichloromethane. After chromatography on 20 g of silica gel using ethyl acetate had been painted a greenish oil. Cleaning was led from toluene. As a result received 91 mg (46%) of N-[2-(4,5-dihydro-6-methoxy-1H-Benz[g]indol-1-yl)ethyl] -ndimethylacetamide with so pl. 133o.

d) 3,34 g (11,7 mmole) of N-[2-(4,5-dihydro-6-methoxy-1H-Benz[g]indol-1-yl)ethyl]-ndimethylacetamide was heated in an argon atmosphere in 75 ml of ethylene glycol/water 2:1 in the presence 3,93 g (58.8 mmol) of potassium hydroxide for 23 h to 140o. After cooling, the reaction mixture was poured into 300 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 30 ml of methanol and treated to 1.61 g (13.8 mmol) of fumaric acid. The precipitated crystals are recrystallized from a total of 140 ml of methanol. The result was obtained 3.8 g (90%) fumarata 2-(4,5-dihydro-6-methoxy-1H-Benz[g]indol-1-yl)-ethylamine (1:1) in the form of yellowish crystals with so pl. 198o.

Example 59

6,30 g (22,2 mmole) of N-[2-(4,5-dihydro-8-methoxy-1H-Benz[g] indol-1-yl)ethyl] -acetone is an increase of 21 h to 140o. After cooling, the reaction mixture was poured into 250 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 100 ml of methanol and was treated with 2.6 g (22.4 mmole) of fumaric acid. The precipitated crystals are recrystallized from a total of 340 ml of methanol. The result was obtained 3.8 g (48%) fumarata 2-(4,5-dihydro-8-methoxy-1H-Benz[g] indol-1-yl)-ethylamine (1: 1) in the form of yellowish crystals with so pl. 183 - 185o.

Example 60

a) cent to 8.85 g (49,0 mmol) of 8-chloro-1-tetralone was dissolved in argon atmosphere in 90 ml of carbon tetrachloride, after which was added to 21.0 ml (245 mmol) of 3-butanol and 190 mg of p-toluenesulfonic acid. The reaction mixture was heated under reflux in a water separator for 9 days. The solvent was removed in vacuo and the residue was chromatographically on 200 g of silica gel using first hexane/ethyl acetate in a ratio of 9:1 and then with hexane/ethyl acetate in the ratio of 4:1. As a result, along with a significant amount of non-reacted educt (8,3 g) was obtained 4.1 g (35%) of 2-(2-butene-1-yl)-8-chloro-1-from 220 ml of dichloromethane and 60 ml of methanol and cooled to -75o, after which the double bond in the usual way was ozonirovanie. After purging the reaction mixture with oxygen and argon was added dropwise 4.8 ml (65,6 mmol) of dimethyl sulfide. Then the mixture was let to slowly warm to room temperature, then stirred for 15 hours the Crude product (10.8 g) was dissolved in about 100 ml of dichloromethane and added to a mixture of 12 ml of 10% aqueous oxalic acid, 120 g of silica gel and 300 ml of dichloromethane. Then was stirred for 2 h at room temperature. After washing with dichloromethane was obtained 6.4 g (83%) of 8-chloro-2-(2 - oxoethyl)-1-tetralone in the form of butter a light brown color.

in) 325 mg (1,46 mmole) of 8-chloro-2-(2-oxoethyl)-1-tetralone and 290 mg (2,84 mmole) of N-acetylethylenediamine was heated under reflux in an argon atmosphere in 14 ml of acetic acid for 1 h the Solvent was removed in vacuo, the residue was dissolved in 10 ml of water and was extracted several times using ethyl acetate. After chromatography on 20 g of silica gel using first hexane/ethyl acetate 1: 1 and then ethyl acetate was obtained 190 mg (45%) of N-[2-(9-chloro-4,5-dihydro-1H-benzo[g] indol-1-yl)ethyl] -ndimethylacetamide in the form of yellowish crystals with so pl. 146-147o.

g) 1.55 g (5.3 mmole) of N-[2-(9-chloro-4,5-dihydro-1H-benzo[g]and the I) of potassium hydroxide for 21 h to 140o. After cooling, the reaction mixture was poured into 60 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 10 ml of methanol and treated to 0.62 g (5.3 mmole) of fumaric acid. The precipitated crystals are recrystallized from a total of 20 ml of methanol. The result obtained 1.26 g (65%) fumarata 2-(9-chloro-4,5-dihydro-1H-benzo[g]indol-1-yl)-ethylamine (4:5) in the form of yellowish crystals with so pl. 181-183o.

Example 61

of 1.80 g (6.2 mmol) of N-[6-chloro-2-(4,5-dihydro-1H-benzo[g]indol-1-yl) ethyl] -ndimethylacetamide was heated in an argon atmosphere in 17 ml of ethylene glycol/water 12:5 in the presence of 0.9 g (16.1 mmol) of potassium hydroxide for 20 h to 140o. After cooling, was treated with 140 ml Polynesians solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The brown oil was chromatographically 50 mg of silica gel using dichloromethane/methanol (first in sootnoshienii acid. The solvent was removed in vacuum and the residue was recrystallized from 50 ml of chloroform/ethanol 4:1. The result has been of 1.41 g (62%) fumarata 2-(6-chloro-4,5-dihydro-1H-benzo[g]indol-1-yl)-ethylamine (1:1) with so pl. 187-188o.

Example 62

0.5 g (1.7 mmole) of N-[7-chloro-2-(4,5-dihydro-1H-benzo[g]indol-1-yl)-ethyl] -ndimethylacetamide was heated in an argon atmosphere in 4.5 ml of ethylene glycol/water 2:1 in the presence of 0.25 g (4.5 mmole) of potassium hydroxide for 22 h to 140o. After cooling, was treated with 40 ml of water and 10 ml of saturated solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 30 ml of diethyl ether was added dropwise to a suspension of 208 mg (1,79 mmole) of fumaric acid in 30 ml of diethyl ether. The solvent was removed in vacuum and the residue was recrystallized from 75 ml of ethanol/ethyl acetate 3: 2. As a result received 355 mg (58%) fumarata 2-(7-chloro-4,5-dihydro-1H-benzo[g]indol-1-yl)-ethylamine (1:1) with so pl. 176-177oin the form of white crystals.

Example 63

1.0 g (3.4 mmole) of N-[8-chloro-2-(4,5-dihydro-1H-benzo[g]indol-1-yl)ethyl] -ndimethylacetamide was heated in an argon atmosphere in 7.5 ml of Oia, the mixture was poured into 75 ml of ice water. After addition of 25 ml of saturated sodium chloride solution was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 20 ml of diethyl ether was added dropwise to a suspension of 406 mg (3,5 mol) of fumaric acid in 80 ml of diethyl ether. The solvent was removed in vacuum and the residue was recrystallized from 90 ml of ethanol/ethyl acetate 5:4. As a result received 556 mg (45%) fumarata 2-(8-chloro-4,5-dihydro-1H-benzo[g] indol-1-yl)-ethylamine (1:1) with so pl. 179 - 180oin the form of white crystals.

Example 64

a) a Solution of 23.9 g (0,145 mole) 4-thiochroman, 30 ml of 0.35 mole) of 3-butene-2-ol and 240 mg of p-toluenesulfonic acid in 30 ml of 2,2-dimethoxypropane and 240 ml of anhydrous toluene was boiled for 20 hours under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result has been of 15.3 g (48%) of (RS)-2-(2-butene-1-yl)-4-thiochroman in the form of a yellow oil.

b) cooled to -70oa solution of 3 g (13.7 mmol) of (RS)-2-(2-butene-1-yl)-4-thiochroman in 100 ml of anhydrous dichloromethane and 30 ml betwo the R for 5 min oxygen for 10 minutes with argon. After addition of 2 ml (20.5 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. After the reaction mixture was evaporated in vacuo, the residue was treated with 50 ml of dichloromethane and, after addition of 5 ml water and 5 ml triperoxonane acid was stirred for 1 h at room temperature. Then the mixture was poured into 50 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 50 ml of water, separated phase and the aqueous phase was extracted twice respectively with 80 ml dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result was obtained 2.8 g (99%) 2-(2 - oxoethyl)-4-thiochroman in the form of a yellow oil, which without further recrystallization was used in subsequent reactions.

C) a Solution of 2 g (9.7 mmol) of (RS)-2-(2-oxoethyl)-4-thiochroman and 120 mg of p-toluenesulfonic acid in 100 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.9 g (38.6 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 20 ml of Cooled reaction mixture of cleansing is-1-(1,4-dihydro-[1]benzothiophene [4,3-b]pyrrol-1-yl)-propan-2-ol in the form of a light brown solid, which without further recrystallization was used in subsequent reactions.

g) cooled to 0oa solution of 1.8 g (7.3 mmol) of (RS)-1-(1,4-dihydro -[1] benzothiophene[4,3-b] pyrrol-1-yl)-propan-2-ol and 4.1 ml (29.3 mmol) of triethylamine in 50 ml of anhydrous dichloromethane under stirring was added dropwise to 1.15 ml (14.7 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 180 ml of diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once were extracted with 70 ml of diethyl ether. The combined organic phases are washed with 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 50 ml of anhydrous dimethylformamide, and treated with 0.96 g (14.7 mmol) of sodium azide and the reaction mixture was heated with stirring for 17 h to 60o. After cooling the solution was poured into 100 ml of water and was extracted twice respectively portions 120 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 100 ml saturated Ichnevogo color was purified by column chromatography on silica gel (toluene). The result has been 1,17 g (59%) of (RS)-1-(2-azithromy)-1,4-dihydro-[1] benzothiophene[4,3-b] pyrrole in the form of a yellowish oil.

d) suspension of 247 mg (of 6.49 mmol) lydialydia in 30 ml of anhydrous tetrahydrofuran under stirring was added dropwise 1,17 g (4.3 mmole) of (RS)-1-(2-azithromy)-1,4-dihydro- [1]benzothiophene[4,3-b] pyrrole dissolved in 30 ml of anhydrous tetrahydrofuran. Then boiled for 2 hours under reflux, after which carried out the hydrolysis with 20% aqueous tetrahydrofuran. The liquid phase was isolated and the residue re-boiled for 15 min with 50 ml of 20% aqueous tetrahydrofuran. United solutions was treated with 100 ml of diethyl ether, the organic phase was isolated and the aqueous phase was twice extracted with respectively 50 ml of diethyl ether. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. As a result received 970 mg (92%) of colorless oil, which was dissolved in 100 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 461 mg (of 3.97 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 3 h at room temperature, patierno[4,3-b]pyrrol-1-yl)-1-methylethylamine (1:1) with so pl. 201o.

Example 65

a) a Solution of 29.5 g (0,22 mole) of 1-indanone is 73.5 ml of 0.85 mole) of Z - butene-2-ol, 77.0 ml (0,63 mole) of 2,2-dimethoxypropane and 400 mg p - toluenesulfonic acid in 400 ml of toluene was heated for 24 h under reflux. After cooling, the solution was washed with 100 ml of saturated solution of sodium bicarbonate. Wash water was extracted with 150 ml of ethyl acetate, the organic phases were combined, dried over magnesium sulfate and evaporated in vacuum. After purification on silica gel (hexane/diethyl ether 7:1) got to 19.8 g (48%) of (RS)-2-(2-butene-1-yl)-1-indanone in the form of oil is light yellow in color.

b) cooled to -70oa solution of 19.8 g (of 0.11 mol) of (RS)-2-(2-butene-1-yl)-1-indanone in 700 ml of anhydrous dichloromethane and 200 ml of anhydrous methanol under stirring missed during 120 min ozone (3 g ozone/hour). Then the solution was purged with oxygen, after which the cold solution was added 11,0 ml of 0.15 mol) of dimethyl sulfide. During the night, the solution was warmed to room temperature and then was evaporated in vacuum. The residue was purified on silica gel (ethyl acetate). The result has been to 10.1 g (43%) of (RS)-2-(2,2-dimethoxymethyl)-1-indanone as a yellow oil.

C) a Solution of 1.7 g (7.7 mmol) of (RS)-2-(2,2-dimethoxymethyl)-1 - indanone, nick within 96 hours After cooling and additives of 21.5 g of sodium hydroxide in 100 ml of water was evaporated to a volume of approximately 100 ml and the Mixture was treated with 200 ml of ethyl acetate and washed successively with 100 ml of saturated solution of sodium chloride, 1H hydrochloric acid (4x100 ml), 2H sodium hydroxide (4x100 ml) and 100 ml of water. The aqueous phase was extracted with 100 ml of ethyl acetate, the combined organic phases were dried over magnesium sulfate and evaporated in vacuum. The residue was purified first basic alumina (111, dichloromethane), and then on silica gel (ethyl acetate). The result was obtained 0.4 g (22%) of N-[2-(1,4-dihydroindeno[1,2-b]pyrrol-1-yl)ethyl]- ndimethylacetamide in the form of a colorless solid.

g) 385 mg (1.6 mmole) of M-[2-(1,4-dihydroindeno[1,2-b]pyrrol-1 - yl)ethyl] -ndimethylacetamide was heated in an argon atmosphere, 6 ml of ethylene glycol/water 2:1 in the presence of 540 mg (9.6 mmol) of potassium hydroxide for 22 h to 140o. After cooling, was treated with 20 ml Polynesians solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts were dried over sodium sulfate, filtered and evaporated. The brown oil was dissolved in 5 ml of methanol and treated 185 (1.59 mmole) of fumaric acid and precipitated light brown crystals, These Wali slow addition of 50 ml of diethyl ether. The resulting product was heated for 1 h in 15 ml of tert.-butyl methyl ether, filtered and dried in vacuum. The result was obtained 220 mg (53%) fumarata 2-(1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-ethylamine (1:0,5) so pl. 201 - 202o.

Example 66

a) a Solution of 29.6 g (of 0.20 mole) of benzoapyrene and 60.9 ml (to 0.80 mole) of N,N-dimethyl hydrazine in 150 ml of anhydrous ethanol was boiled for 3 days under reflux. The ethanol and excess N,N-dimethylhydrazine was removed in vacuo, the residue was dissolved in dichloromethane and dried with magnesium sulfate. After distillation on a column of Vigro (10 cm) was obtained from 32.9 g (83%) benzocoumarin-N',N'-dimethylhydrazine in the form of a yellow oil. So pl. 78 - 81oC/0,210-3the ATM.

b) In an argon atmosphere a solution of 33.6 g (to 0.17 mole) of benzocoumarin - N',N'-dimethylhydrazine and 29.9 ml of 0.20 mol) of tetramethylethylenediamine in 400 ml of absolute tetrahydrofuran was cooled to -70oand for 15 min was added dropwise 106 ml of a 1.6 M solution of n-utility in hexane. Then was stirred for 30 min at -70owas allowed to warm to -30oand to the mixture at this temperature for drops added bromoacetaldehyde in the amount of 23.4 ml of 0.20 mol). After stirring for 1.5 h at -30othe mixture was allowed to heat up the m (h, 2x500 stretch-forming press ml), the organic phases were combined, dried with magnesium sulfate and evaporated in vacuum. After chromatography on silicagel column (hexane/ethyl acetate 10: 1-3: 1) received of 37.7 g (78%) of (RS)-2-(2,2-dimethoxymethyl)- benzocoumarin-N', N'-dimethylhydrazine in the form of oil of orange-yellow color.

C) Suspension of 37.7 g (0,13 mol) of (RS)-2-(2,2-dimethoxymethyl)- benzocoumarin-N',N'-dimethylhydrazine, 30,2 g (of 0.37 mole) of sodium acetate and 78.8 g (of 0.37 mole) of periodate sodium in 2000 ml of tetrahydrofuran was treated with 300 ml of acetic acid and was stirred over night at 50o. Then the mixture was cooled, poured into 3000 ml of water and was extracted with dichloromethane (h, h ml). The organic phases were combined, dried with magnesium sulfate and concentrated in vacuum. After chromatography on silicagel column (hexane/ethyl acetate 2:1) along with 9.7 g (26%) of the original substance was received of 8.2 g (25%) (RS)-2-(2,2-dimethoxymethyl)-benzocoumarin in the form of oil red.

g) of 8.2 g of (RS)-2-(2,2-dimethoxymethyl)-benzocoumarin was chromatographically on a column with adsorbed on silica gel solution of oxalic acid (180 g of silica gel/20 ml 10% aqueous solution of oxalic acid). The result was obtained 6.2 g (90%) of (RS)-2-(2-oxoethyl)-benzocoumarin in the form of oil Krasniy in 50 ml of anhydrous dichloromethane was treated with 50 g of molecular sieve 4 and during the night boiled under reflux. After cooling, filtered through Celite, evaporated in vacuo and the residue was recrystallized from hexane/ethyl acetate 2:1. The result was obtained 4.0 g (50%) N-[2-(1,4,5,6 - tetrahydrobenzo[6,7]cyclohepta[1,2-b]pyrrol-1-yl)ethyl]-ndimethylacetamide in the form of a colorless solid.

e) of 1.80 g (6.7 mmol) of N-[2-(1,4,5,6 - tetrahydrobenzo[6,7]cyclohepta[1,2-b] pyrrol-1-yl)ethyl] - ndimethylacetamide was heated in an argon atmosphere in 18 ml of ethylene glycol/water 2:1 in the presence of 1.0 g (17.8 mmol) of potassium hydroxide for 24 h to 140o. After cooling, the reaction mixture was poured into 140 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts once washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. Thus obtained oil was chromatographically on 60 g of silica gel using methylene chloride/methanol 19:1. The crude product was dissolved in 5 ml diethyl ether and treated 505 mg (4.35 mmole) of fumaric acid in 10 ml of diethyl ether. The crystals were filtered off and recrystallized from 50 ml of ethyl acetate/ethanol 2:1. The result has been of 1.65 g (72%) fumarata 2-(1,4,5,6 - tetrahydrobenzo[6,7]cyclohepta[1,2-b]pyrrol-1-yl)-ethylamine (1: 1) in a V is, 3.6 ml (to 0.39 mol) C-butene-2-ol and 265 mg of p-toluenesulfonic acid in 33.6 ml of 2,2 - dimethoxypropane and 265 ml of anhydrous toluene was heated for 17 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). The result has been to 9.9 g (28%) of (RS)-2- (2-butene-1-yl)-7-methoxy-1-indanone as a yellow oil.

b) cooled to -70oa solution of 9.9 g (45.8 mmol) of (RS)-2-(2-butene-1-yl)-7-methoxy-1-indanone in 200 ml of anhydrous dichloromethane and 100 ml of anhydrous methanol was passed with stirring for 45 min the flow of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After addition of 5 ml (67.7 mmol) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 200 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 3 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was extracted twice sooooo in vacuum and the resulting crude product was led from ethyl acetate/hexane. The result obtained 6.6 g (71%) of (RS)-2-(2-oxoethyl)- 7-methoxy-1-indanone as a white solid with so pl. 102o.

C) the Solution 2,04 g (10 mmol) of (RS)-2-(2-oxoethyl)-7-methoxy-1 - indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.0 g (40 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 25 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2:3). The result was obtained 1.1 g (45%) of (RS)-1-(8-methoxy-1,4-dihydroindeno[1,2 - b]pyrrol-1-yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

g) cooled to 0oa solution of 1.1 g (4.5 mmole) of (RS)-1-(8-methoxy - 1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.5 ml (18.0 mmol) of triethylamine in 25 ml of dichloromethane under stirring was added dropwise 0.7 ml (9.0 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml Nasyrova ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated 526 mg (8.1 mmol) of sodium azide and the reaction mixture was heated with stirring for 29 h 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.68 g (56%) of (RS)-1-(2-azithromy)-8-methoxy-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

d) of 0.67 g (2.5 mmole) of (RS)-1-(2-azithromy)-8-methoxy-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 25 ml of anhydrous ethanol, was first made in the presence of 67 mg of platinum oxide for 5 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 70 ml of anhydrous ditillio is Nola. Then was stirred for 22 h at room temperature, then was filtered white crystals. The result obtained 559 mg (74%) fumarata (RS)-2- (8-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 193o.

Example 68

a) a Solution of 23.3 g (0,105 mol) of (RS)-3-phenyl-1-tetralone, to 21.6 ml of 0.25 mol) C-butene-2-ol and 230 mg of p-toluenesulfonic acid in 21.6 ml of 2,2-dimethoxypropane and 230 ml of anhydrous toluene was heated for 30 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4: 1). The result has been to 11.8 g (41%) of (2RS/3RS)-2-(2-butene-1-yl)-3-phenyl-1-tetralone in the form of oil red.

b) cooled to -70oa solution of 11.8 g (42,7 mmole) of (2RS/3RS)-2-(2-butene-1-yl)-3-phenyl-1-tetralone in 300 ml of anhydrous dichloromethane and 100 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 4.45 ml (60.8 mmol) of dimethyl sulfide was stirred for 17 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 300 ml of dichloromethane and after doby was poured into 100 ml of water and with stirring, neutralized, adding with a spatula sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was purified by column chromatography on silica gel (toluene/ethyl acetate 9: 1). The result obtained 9.7 g (86%) of (2RS/3RS)-2-(2-oxoethyl)-3-phenyl-1-tetralone as a yellow oil.

C) a Solution of 2 g (7.6 mmol) of (2RS/3RS)-2-(2-oxoethyl)-3-phenyl-1 - tetralone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2.18 g (29,0 mmol) (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then kept boiling for 30 min, and the volume of solvent was reduced to 25 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:9). The result was obtained 1.04 g (45%) of (2RS/4RS)-1- (4,5-dihydro-4-phenyl-1H-benzo[g]indol-1-yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

g) cooled to 0oa solution of 1.04 g (3.4 mmole) of (2RS/4RS)-1-(4,5 - digital dropwise of 0.53 ml (6.8 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 130 ml of diethyl ether. The combined organic phases are washed with 100 ml saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 25 ml of anhydrous dimethylformamide was treated with 0.45 g (6.8 mmol) of sodium azide and the reaction mixture was heated under stirring for 6 hours to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 100 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). As a result received 473 mg (42%) of (2RS/4RS)-1-(2-azithromy)-4,5-dihydro-4-phenyl-1H-benzo[g] indole as a colorless oil.

d) 473 mg (1.44 mmole) of (2RS/4RS)-1-(2-azithromy)-4,5-dihydro-4-phenyl-1H-benzo[g] indole dissolved in 20 ml besod is a, washed with ethanol and the solvent is kept in vacuum. The obtained colorless oil was dissolved in 40 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 148 mg (1,28 mmole) of fumaric acid in 5 ml of methanol. Then was stirred for 7 h at room temperature, then was filtered white crystals. As a result received 446 mg (74%) fumarata (2RS/4RS)-2-(4,5-5 dihydro-4-phenyl-1H-benzo[g] indol-1-yl)-1-methylethylamine (1:1) with so pl. 187o.

Example 69

a) a Solution of 20 g (96 mmol) of (RS)-3-phenyl-1-indanone, 20 ml (to 0.23 mole) of Z-butene-2-ol and 200 mg of p-toluenesulfonic acid in 20 ml of 2,2 - dimethoxypropane and 200 ml of anhydrous toluene was heated for 22 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 5:1). As a result received 10 g (40%) of (2RS/3RS)-2-(2-butene-1-yl)-3-phenyl-1 - indanone as a yellow oil.

b) cooled to -70oa solution of 10 g (38.1 mmol) of (2RS/3RS)-2-(2-butene-1-yl)-3-phenyl-1-indanone in 200 ml of anhydrous dichloromethane and 70 ml of anhydrous methanol under stirring missed for 40 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and techoperators. The reaction mixture was evaporated in vacuo, the residue was treated with 150 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 1 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated in vacuum. The result was obtained 9.5 g (99%) of (2RS/3RS)-2-(2-oxoethyl)-3-phenyl-1-indanone in the form of oil, which without further recrystallization was used in subsequent reactions.

C) a Solution of 3.0 g (12 mmol) of (2RS/3RS)-2-(2-oxoethyl)-3-phenyl-1-indanone and 100 mg p-toluenesulfonic acid in 100 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 3.6 g (48 mmol) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 25 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl - zett/toluene 1:1). The result was obtained 2.4 g of the Wali in subsequent reactions.

g) cooled to 0oa solution of 2.3 g (7.9 mmol) of (2RS/4RS)-1-(4 - phenyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and of 4.46 ml (to 31.8 mmol) of triethylamine in 60 ml of dichloromethane under stirring was added dropwise to 1.24 ml (15.9 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 140 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 60 ml of anhydrous dimethylformamide, treated 884 mg (13.6 mmol) of sodium azide and the reaction mixture was heated with stirring for 16 h to 60o. After cooling the solution was poured into 140 ml of water and was extracted twice respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. Received the 1.22 g (49%) of (2RS/4RS)-1-(2-azithromy)-4-phenyl-1,4-dihydroindeno[1,2-b] pyrrole in the form of oil, slightly stained in brown color.

d) 1.2 g (3.8 mmole) of (2RS/4RS)-1-(2-azithromy)-4-phenyl-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 120 mg of platinum oxide for 5 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 100 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 480 mg (4,13 mmole) of fumaric acid in 20 ml of methanol. Then was stirred for 16 h at room temperature, then was filtered crystals. The result was obtained 1.04 g (65%) fumarata (2RS/4RS)-2- (4-phenyl-1,4-dihydroindeno [1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,86) so pl. 191o.

Example 70

a) of 13.7 g (77,0 mmol) of 8-methoxy-1-tetralone was dissolved in argon atmosphere in 140 ml of toluene, then added to 13.3 ml (155 mmol) of 3-butene-2-ol, of 14.2 ml (116 mmol) of 2,2-dimethoxypropane and 300 mg of p-toluenesulfonic acid. The solution was heated for 90 hours under reflux. The solvent was removed in vacuo and the residue was chromatographically on 500 g of silica gel using first hexane/ethyl acetate in a ratio of 9:1, then hexane/ ethyl acetate in the ratio of 4:1 and, finally, the product (8,3 g) received 3,95 g (22%) of 2-(2-butene-1-yl)- 8-methoxy-1-tetralone as a yellow oil.

b) 11.4 g (49.5 mmol) of 2-(2-butene-1-yl)-8-methoxy-1-tetralone was dissolved in a mixture of 340 ml of dichloromethane and 100 ml of methanol, then was cooled to -75oand ozonirovanie double bond in the usual manner. After purging the reaction mixture with oxygen and argon was added dropwise to 7.2 ml (a 99.0 mmol) of dimethyl sulfide. The mixture was allowed to warm to room temperature and was stirred for 17 hours, the Solvent was removed in vacuo, the residue was dissolved in 200 ml diethyl ether and washed with water. Then was dried with sodium sulfate, filtered and evaporated, and receive 10.6 g of a mixture of dimethylacetal and aldehyde. 7.0 g of this mixture was dissolved in 70 ml of methylene chloride and added to a mixture of 8.4 ml of 10% aqueous oxalic acid, 80 g of silica gel and 210 ml of dichloromethane. Then was stirred for 2 h at room temperature. As a result of leaching using dichloromethane /diethyl ether 9:1 was obtained 5.6 g of 8-methoxy-2-(2 - oxoethyl)-1-tetralone in the form of a light brown oil.

in) 400 mg (1.8 mmole) of 8-methoxy-2-(2-oxoethyl)-1-tetralone was heated under reflux in an argon atmosphere with 205 mg (2.0 mmole) N-acetylethylenediamine in 8 ml of toluene for 15 minutes Then the solvent was removed in vacuo and the residue was chromatographically no 280 mg (54%) of N-[2-(4,5-dihydro-9-methoxy-1H-Benz[g]indol-1-yl)ethyl]-ndimethylacetamide in the form of yellowish crystals with so pl. 132-133o.

g) 2.3 g (8.0 mmol) of N-[2-(4,5-dihydro-9-methoxy-1H-Benz[g]indol-1-yl) ethyl] -ndimethylacetamide was heated in an argon atmosphere in 23 ml of ethylene glycol/water 2:1 in the presence of 2.70 g (48.2 mmol) of potassium hydroxide for 16 h to 140o. After cooling, the reaction mixture was poured into 200 ml policecontributing solution of sodium chloride. Then was extracted three times with diethyl ether, the United extracts were washed once with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated. The crude product was dissolved in 20 ml of methanol and treated with 0.93 g (8.0 mmol) of fumaric acid. The precipitated crystals are recrystallized from a total of 70 ml of methanol. The result has been 1,76 g (61%) fumarata 2-(4,5-dihydro-9-methoxy-1H - Benz[g]indol-1-yl)-ethylamine (1:1) in the form of yellowish crystals with so pl. 184 - 185o.

Example 71

a) a Solution of 21.5 g (0,13 mol) of 4-methoxy-1-indanone, a 27.4 ml of 0.32 mol) C-butene-2-ol and 210 mg of p-toluenesulfonic acid in a 27.4 ml of 2,2 - dimethoxypropane and 210 ml of anhydrous toluene was heated for 16 h under reflux. Then the reaction mixture was concentrated in vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 9:1). In Jdenny to -70oa solution of 6.42 per g (29.7 mmol) of (RS)-2-(2-butene-1-yl)-4-methoxy-1-indanone in 180 ml of anhydrous dichloromethane and 60 ml of anhydrous methanol under stirring missed during 35 min stream of ozone (3 g ozone/hour). Then the solution was purged for 5 min with oxygen and for 10 min with argon. After the addition of 3.3 ml (44,7 mmole) of dimethyl sulfide was stirred for 16 h at room temperature. The reaction mixture was evaporated in vacuo, the residue was treated with 200 ml of dichloromethane and, after addition of 20 ml water and 20 ml triperoxonane acid was stirred for 2 h at room temperature. Then the mixture was poured into 100 ml of water and with stirring, neutralized by adding with a spatula sodium bicarbonate. After this was added 100 ml of water, separated phase and the aqueous phase was twice extracted respectively by portions of 150 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and the resulting crude product was led from ethyl acetate/hexane. The result has been to 5.1 g (84%) of (RS)-2-(2-oxoethyl)-4-methoxy-1-indanone as a white solid with so pl. 71o.

C) the Solution 2,04 g (10 mmol) of (RS)-2-(2-oxoethyl)-4-methoxy-1-indanone and 80 mg of p-toluenesulfonic acid in 90 ml of anhydrous t is) (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for 35 min, and the volume of solvent was reduced to 25 ml of Cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 1:4). The result was obtained 0.7 g (29%) of (RS)-1-(5-methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1 - yl)-propan-2-ol as a brown oil, which was directly used in the subsequent reaction.

g) cooled to 0oa solution of 0.7 g (2.9 mmole) of (RS)-1-(5-methoxy-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)- propan-2-ol and 1.6 ml (11.5 mmol) of triethylamine in 20 ml of dichloromethane under stirring was added dropwise to 0.45 ml (5,77 mmol) methanesulfonanilide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was diluted with 200 ml diethyl ether, washed twice respectively portions 70 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases once was extracted with 140 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 20 ml of anhydrous dimethylformamide, treated 366 mg (5.6 mmol) of sodium azide and reacciona who was twice extracted respectively portions 140 ml of diethyl ether. The combined organic phases are washed once respectively 140 ml of water and 140 ml of a saturated solution of sodium chloride, dried over magnesium sulfate and the solution was concentrated in vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result was obtained 0.55 g (73%) of (RS)-1-(2-azithromy)-5-methoxy - 1,4-dihydroindeno[1,2-b] pyrrole as a colorless oil.

d) of 0.54 g (2.0 mmole) of (RS)-1-(2-azithromy)-5-methoxy-1,4 - dihydroindeno [1,2-b] pyrrole dissolved in 20 ml of anhydrous ethanol, was first made in the presence of 54 mg of platinum oxide for 17 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 50 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 110 mg (0.95 mmole) of fumaric acid in 10 ml of methanol. Then was stirred for 22 h at room temperature, then was filtered white crystals. As a result received 500 mg (83%) fumarata (RS)-2-(5 - methoxy - 1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 194o.

Example 72

a) a Solution of 0.95 g (3.1 mmole) of (2RS/4RS)-2-(4,5-dihydro-4-phenyl-1H - benzo[g]indol-1-yl)-1-mutilate is within 30 min to 50o. Then the reaction mixture was poured on ice and treated with 70 ml of saturated solution of sodium bicarbonate. Then was extracted twice respectively with 100 ml dichloromethane, the combined organic phases are once washed with cold 3H sulfuric acid and once with cold saturated solution of sodium bicarbonate. After drying the solution over magnesium sulfate, the solvent is kept in vacuum and the residue was dissolved in 40 ml of anhydrous dioxane. Then added 729 mg (3,21 mmole) BCH and boiled for 1 h under reflux, after which the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (dichloromethane/methanol 20: 1). The result has been 0,69 g (64%) of (RS)-N-[2-(4-(phenyl-1H-benzo[g]indol-1-yl)-1-methylethyl]-ndimethylacetamide in the form of a light brown solid, which without further recrystallization use in subsequent reactions.

b) a Mixture of 670 mg (1,96 mmole) of (RS)-N-[2-(4-phenyl-1H-benzo[g]indol-1 - yl)-1-methylethyl] -ndimethylacetamide, 1,32 g (23.4 mmol) of potassium hydroxide in 15 ml of water and 30 ml of ethylene glycol was heated for 46 h under reflux. Then the reaction mixture was poured into 80 ml of a saturated solution of sodium chloride and was extracted twice on solution of sodium chloride and dried over magnesium sulfate. After concentration in vacuo the residue was purified by column chromatography on silica gel (dichloromethane/methanol 9:1) and the oil obtained [308 mg (equivalent to 1.03 mmole)] was dissolved in 30 ml of anhydrous diethyl ether, filtered and with stirring, treated with a solution of 119 mg (equivalent to 1.03 mmole) of fumaric acid in 6 ml of methanol. Then was stirred for 20 h at room temperature, then was filtered white crystals. As a result received 308 mg (41%) fumarata (RS)-2-(4-phenyl-1H-benzo[g] indol-1-yl)-1 - methylethylamine (1:0,7) so pl. > 230o.

Example 73

a) cooled to -70othe solution 2,96 g (18.3 mmol) of 6-methoxy-1-indanone in 300 ml of anhydrous tetrahydrofuran under stirring was added dropwise within 10 min prepared at 0ofrom 3,12 ml (22 mmole) of Diisopropylamine and 13.8 ml (22 mmole) n-utility (1.6 N in hexane) solution of LDA (sitedisability) in 40 ml of anhydrous tetrahydrofuran. After 30 minutes in this solution for 5 min was added dropwise a solution of 1.62 ml (20.2 mmol) of chloroacetone in 40 ml of anhydrous tetrahydrofuran, and then was stirred for 2 h at room temperature. Then the reaction mixture was poured into 150 ml of ice was added 150 ml of a saturated solution of sodium chloride and twice is washed with 200 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and concentrated in vacuum. The resulting crude product was purified by column chromatography on silica gel (hexane/diethyl ether first in the ratio 3:2, and then 2:3). The result was obtained 1.8 g (45%) of (RS)-6-methoxy-2-(2-oxopropyl)-1-indanone in the form of oil red.

b) a Solution of 1.8 g (8.3 mmol) of (RS)-6-methoxy-2-(2-oxopropyl)-1-indanone and 70 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 2,48 g (33 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for another 3 h, and the volume of solvent was reduced to 30 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been to 1.37 g (65%) of (RS)-1-(7-methoxy-2-methyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of a solid substance with so pl. 110o.

in) cooled to 0oa solution of 1.35 g (5.3 mmol) of (RS)-1-(7 - methoxy-2-methyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.9 ml (20.9 mmol) of triethylamine in 40 ml of dichloromethane under stirring was added dropwise 0,81 ml (10.5 mmol) of methanesulfonamide and continued plumage is listed respectively in portions of 100 ml of dichloromethane and the combined organic phases are washed once respectively 70 ml of saturated sodium hydrogen carbonate solution and 70 ml of saturated solution of sodium chloride, was dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide was treated with 0.68 g (10.5 mmol) of sodium azide and the reaction mixture was heated with stirring for 23 h to 80o. After cooling the solution was poured into 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 0,93 g (62%) of (RS)-1-(2-azithromy)-7-methoxy-2-methyl-1,4-dihydroindeno [1,2-b] pyrrole as a colorless oil.

g) to 0.92 g (3.3 mmole) of (RS)-1-(2-azithromy)-7-methoxy-2-methyl-1,4-dihydroindeno [1,2-b] pyrrole dissolved in 70 ml of anhydrous ethanol, was first made in the presence of 90 mg of platinum oxide for 16 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 70 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 160 mg (1.4 mm which was filtered white crystals. As a result received 800 mg (78%) fumarata (RS)-2-(7 - methoxy-2-methyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 187 - 188o.

Example 74

a) cooled to -70othe solution 3,24 g (20 mmol) 5-methoxy-1-indanone in 350 ml of anhydrous tetrahydrofuran under stirring was added dropwise within 15 min prepared at 0ofrom 4,25 ml (30 mmol) of Diisopropylamine and 18.8 ml (30 mmol) n-utility (1.6 N in hexane) solution of LDA in 60 ml of anhydrous tetrahydrofuran. After 45 min in this solution for 15 min was added dropwise a solution of 1.6 ml (20 mmol) of chloroacetone in 60 ml of anhydrous tetrahydrofuran, and then was stirred for 2 h at room temperature. Then the reaction mixture was poured into 150 ml of ice was added 150 ml of a saturated solution of sodium chloride and was extracted twice respectively in portions of 300 ml of diethyl ether. The combined organic phases are once washed with 200 ml saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuum. The resulting crude product was purified by column chromatography on silica gel (hexane/diethyl ether 3:7). The result was obtained 1.4 g (32%) of (RS)-5-methoxy-2-(2-oxopropyl)-1-indanone in the form of solid persulphate in 70 ml of anhydrous toluene was heated in a water separator. In the boiling solution for 5 min was added dropwise a solution of 1.65 g (22 mmole) of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene. Then continued to boil for another 3 h, and the volume of solvent was reduced to 30 ml of Cooled reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). The result has been 1,17 g (82%) of (RS)-1-(6-methoxy-2 - methyl-1,4 - dihydroindeno[1,2-b]pyrrol-1-yl)-propan-2-ol in the form of butter.

in) cooled to 0oa solution of 1.16 g (4.5 mmole) of (RS)-1-(6 - methoxy-2-methyl-1,4-dihydroindeno[1,2-b] pyrrol-1-yl)-propan-2-ol and 2.5 ml (18 mmol) of triethylamine in 50 ml of dichloromethane under stirring was added dropwise 0.7 ml (9.0 mmol) of methanesulfonamide and continued to stir for 1.5 h at this temperature. Then the reaction mixture was poured into 70 ml of water, was extracted twice respectively with 100 ml dichloromethane and the combined organic phases are washed once respectively 70 ml of saturated sodium hydrogen carbonate solution and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and evaporated in vacuum. The obtained brown oil was dissolved in 40 ml of anhydrous dimethylformamide, treated of 0.58 g (9.0 mmol) asydayslovalm in 70 ml of water and was extracted twice respectively with 100 ml of ethyl acetate. The combined organic phases are washed once respectively 70 ml of water and 70 ml of saturated solution of sodium chloride, dried over magnesium sulfate and concentrated solution in a vacuum. The obtained brown oil was purified by column chromatography on silica gel (toluene). The result has been 0,86 g (55%) of (RS)-1-(2-azithromy)-6-methoxy-2-methyl-1,4-dihydroindeno [1,2-b]pyrrole as a colorless oil.

g) of 0.85 g (3.0 mmole) of (RS)-1-(2-azithromy)-6-methoxy-2 - methyl-1,4-dihydroindeno[1,2-b] pyrrole dissolved in 50 ml of anhydrous ethanol, was first made in the presence of 85 mg of platinum oxide for 17 hours and Then was filtered from the catalyst, washed with ethanol and drove the solvent in vacuo. The obtained colorless oil was dissolved in 70 ml of anhydrous diethyl ether, filtered and treated with stirring with a solution of 155 mg (1.3 mmole) of fumaric acid in 15 ml of methanol. Then was stirred for 19 h at room temperature, then was filtered white crystals. As a result received 780 mg (83%) fumarata (RS)-2-(6-methoxy - 2-methyl-1,4-dihydroindeno [1,2-b] pyrrol-1-yl)-1-methylethylamine (1:0,5) so pl. 215o.

An example of A

The usual procedure is to produce tablets next SOS the rod, specified in the table. 5.

The example IN

The production of capsules of the following composition, given in table. 6.

The active substance with the appropriate particle size, crystalline lactose and microcrystalline cellulose are thoroughly mixed to obtain a homogeneous mass, pass through a sieve, then add talc and magnesium stearate and mix. Then the resulting mixture is made tverdoplamennoe capsules of appropriate size.

1. Tricyclic derivatives of pyrrole of the formula I

< / BR>
where R1- R4denotes hydrogen, halogen, lower alkyl, phenyl, cycloalkyl or lower alkoxy, R2means are also lower alkoxycarbonyl, acyloxy or mesilate;

R5denotes lower alkyl;

R6and R7represent hydrogen or lower alkyl;

X denotes-CH2CH(C6H5)-, -CH= C(C6H5), USN2-, -CH= CH - or -(CR11R12)p;

R11and R12denote hydrogen, phenyl or lower alkyl;

n denotes 1 - 3;

Y represents 0 or S,

and their pharmaceutically acceptable acid additive salt.

2. Connection on p. 1, where R5on the Sabbath. denotes halogen, lower alkyl or methoxy.

4. Connection on p. 1, which represents the (S)-2-(4,4,7-trimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methyl-ethylamine.

5. Connection on p. 1, which represents the (S)-2-(7-methoxy-4,4-dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl-methyl-ethylamine.

6. Connection on p. 1, which represents the (S)-2-(7-ethyl-4,4-dimethyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methyl-ethylamine.

7. Connection on p. 1, which represents the (S)-2-(7-methyl-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)1-methyl-ethylamine.

8. Connection on p. 1, which represents the (S)-2-(7-bromo-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methyl-ethylamine.

9. Connection on p. 1, which represents the (S)-2-(7-methoxy-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methyl-ethylamine.

10. Connection on p. 1, which represents the (S)-2-(7-chloro-1,4-dihydroindeno[1,2-b]pyrrol-1-yl)-1-methyl-ethylamine.

11. Connection on p. 1, which represents the (S)-2-(8-methoxy-1H-Benz(e)indol-1-yl)-1-methyl-ethylamine.

12. Pharmaceutical drug that is capable of binding to serotonin receptors containing the active substance, one or more therapeutically acceptable fillers and possible additives, characterized in that as the active R>
17.08.94 - PP.4 - 7.

 

Same patents:

The invention relates to new compounds having pharmacological activity, to a method of their preparation and use as pharmaceuticals

The invention relates to new chemical substances, which have valuable pharmacological properties, more particularly to a nitrogen-containing heterocyclic compounds of General formula I

< / BR>
where X is oxygen or sulfur;

Y is carbon or nitrogen;

Z is carbon or nitrogen, and Y and Z are not simultaneously mean nitrogen;

R1and R2independent from each other and denote hydrogen, alkyl with 1 to 6 carbon atoms, halogen, trifluoromethyl, nitrile, alkoxy with 1 to 6 carbon atoms, a group of CO2R7where R7means hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)NR8R9where R8and R9not dependent from each other and denote hydrogen, alkyl with 1 to 3 carbon atoms, methoxy or together with the nitrogen form a morpholine, pyrrolidine or piperidine-NR10R11where R10and R11denote hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)R12where R12means alkyl with 1 to 6 carbon atoms, group-SO2R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has a specified value, and-SO2NR13R14where R13and R142R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has the specified value, -SO2NR13R14where R13and R14have a specified value, a nitrogroup, 1-piperidinyl, 2-, 3 - or 4-pyridine, morpholine, thiomorpholine, pyrrolidine, imidazole, unsubstituted or substituted at the nitrogen by alkyl with 1 to 4 carbon atoms, 2-thiazole, 2-methyl-4-thiazole, dialkylamino with 1 to 4 carbon atoms in each alkyl group, or alkilany ether with 1 to 4 carbon atoms;

R4an ester of formula-CO2R16where R16means alkyl with 1 to 4 carbon atoms, the amide of formula C(O)NR17R18where R17and R18independent from each other and denote hydrogen, alkyl with 1 to 2 carbon atoms, methoxy or together with the nitrogen form a morpholine, piperidine or pyrrolidine, phenyl, unsubstituted or substituted by residues from the group comprising halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, 3-methyl-1,2,4-oxadiazol-5-yl, 2 - or 3-thienyl, 2-, 3 - or 4-pyridyl, 4-pyrazolylborate 4 stands, the ketone of the formula C(O)R19'where R19means alkyl with 1 to 3 carbon atoms, phenyl or 1-Mei-2-yl, a simple ester of the formula-CH2OR20where R20means alkyl with 1 to 3 carbon atoms, thioether formula-CH2SR20where R20has the specified value, the group CH2SO2CH3amines of the formula-CH2N(R20)2where R20has the specified value, the remainder of the formula-CH2NHC(O)R21where R21means methyl, amino or methylamino - group-CH2NHSO2Me2where Me denotes methyl carbamate of the formula CH2OC(O)NHCH3;

R5and R6independent from each other and denote hydrogen or methyl;

n is 0,1 or 2,

Provided that the substituents are not simultaneously have the following meanings: Y and Z is carbon, R1or R2hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, cyano, nitro, trifluoromethyl, R3unsubstituted phenyl and R4group-C(O)OR16'where R16'means hydrogen, alkyl, alkenyl or quinil, group-C(O)N(R18')(R19'), where R18'and R19'denote hydrogen, alkyl with 1 to 6 carbon atoms, phenyl, alkoxy or together with the nitrogen form pyrrolidine, piperidine or morpholine, cyanotic, unsubstituted phenyl and 4-imidazole,

in the form of a racemate or an individual enantiomers and their salts, are inhibitors of leukotriene biosynthesis

The invention relates to new cephalosporins, namely to derive 1-zetia-diazaphosphorines General formula 1:

(I)

where the wavy line represents a CIS - or TRANS-configuration; R1-C1-C4alkyl, if necessary, replaced by carboxypropyl;

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The invention relates to chemical compounds with valuable properties, in particular derivatives of 2,3-dihydropyrano[2,3-b] pyridine of General formula

< / BR>
(I) where a lower alkylene;

R is a hydrogen atom or a group

A< / BR>
or their salts

The invention relates to methods for tetrahydrobenzo(C, d) antolovich derivatives of General formula Iwhere R1- hydrogen Ilai1- C4-alkyl,

R2- C1-C4-alkyl

The invention relates to new derivatives of Anthranilic acid of General formula (1) or their pharmacologically acceptable salts, where R1, R2, R3and R4- same or different and mean a hydrogen atom, halogen atom, optionally halogenated lower alkoxygroup, nitro, cyano, pyrazolidine group, a group of the formula (II), where R9and R10are the same or different and mean a hydrogen atom, a lower alkyl group and p is an integer from 0 to 6, a group of the formula (III), where R13represents a hydrogen atom, a lower alkyl group, q is an integer from 0 to 2; and R2may be 1,2,4-triazoline group; R5and R6are the same or different and represent a hydrogen atom, halogen atom, cyano, lower alkoxygroup, or R5and R6together with the carbon atoms to which they are attached, form oxolane ring, 1,3-dioxolane or 1,4-dioxane ring; W represents a group - N = or-CH=; R7and R8are the same or different and represent a hydrogen atom, a lower alkyl group, or R1and R7together with the carbon atoms and nitrogen, respectively, to which they are attached, form the second alkyl group or a group of the formula-X-(CH2)m-Z, where X represents-CO-, -CH2- or-S(O)2-; Z represents hydrogen, halogen, phenyl group which may be substituted by lower alkyl, lower alkoxygroup, carboxypropyl or lower alkoxycarbonyl group, pyridyloxy group, a group of the formula NR11R12where R11and R12together with the nitrogen atom to which they are attached, form piperidino or pyrolidine ring which may be substituted by a lower alkyl group, actigraphy, carboxypropyl, lower alkoxycarbonyl group, cycloalkyl group containing 3-8 carbon atoms which may be substituted by actigraphy, cyano, lower alkylcarboxylic, carboxypropyl or lower alkoxycarbonyl group, piperidino group, m is an integer from 0 to 6, Y is an oxygen atom; n is an integer from 0 to 6
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