Nucleic base having perfluoroalkyl group and synthesis method thereof

FIELD: chemistry.

SUBSTANCE: nucleic base (e.g. uracil, cytosine, adenine, guanine, hypoxanthine, xanthine or similar) reacts with perfluoroalkyl halide in the presence of sulphoxide, peroxide and an iron compound to obtain a perfluoroalkyl-substituted nucleic base.

EFFECT: high cost effectiveness as an intermediate compound for producing medicinal agents.

15 cl, 6 tbl

 

The scope of the invention

The present invention relates to a method of obtaining a nucleic base, having performanceline group.

The level of technology

Nucleic bases, substituted perforaciones group, are useful compounds as pharmaceuticals and intermediates for medical and agricultural chemicals, in this case, nucleic bases, with triptorelin group, are especially useful compounds. In this regard, there have been numerous studies of the processes of obtaining triftorperasin nucleic bases.

As for the method of producing 5-cryptomaterial, which is important as an intermediate connection to create an anticancer agent, an antiviral agent, or the like, for example, patent document 1 discloses a method of obtaining a 5-cryptomaterial the interaction of 5-trifluoromethyl-5,6-dihydrouracil, which is produced by the interaction of α-cryptomaterial acid and urea, dimethylsulfoxide and iodine in the presence of concentrated sulfuric acid as catalyst. In addition, Patent document 2 discloses a method of interaction between 5-iodouracil with copper iodide and methylbenzylphosphonate, with subsequent conversion of then 5-triftormyetil. Moreover, patent document 3 discloses a method of obtaining a 5-cryptomaterial, in which thymine hairout such as chlorine gas, to obtain 2,4-dichloro-5-trichloromethylpyridine, which is then foryouth anhydrous hydrofluoric acid or antimony TRIFLUORIDE in the presence of pentachloride antimony, followed by treatment with water. However, these methods have disadvantages, because they all are multi-stage and in the latter method uses anhydrous hydrofluoric acid and a compound of antimony, which is industrially difficult to operate. In addition, non-Patent document 1 discloses a method of triptoreline 3',5'-diacetyl-2'-dose irradiation on neurogenesis in the 5-position triperoxonane acid and diferida xenon. However, this method also uses a special reagent and is industrially difficult to implement.

In addition, as for the method of producing 5-triptoreline, non-Patent document 2 discloses a method of obtaining a 5-triptoreline hydrolysis of 4-amino-2-chloro-5-cryptomaterial obtained by the interaction of 2,4-dichloro-5-cryptomaterial and liquid ammonia, followed by treatment of its ion-exchange resin. However, this method has the disadvantage that is associated with multi-stage, including obtaining raw foods.

As for the method of obtaining such compounds as purine, having triptorelin group, for example, non-Patent document 3 discloses a method of obtaining 8-triptoreline, 2,6-diamino-8-triptorelin and 8-triftormetilfosfinov interaction 4,5-diaminopyrimidine with triperoxonane acid or triperoxonane anhydride. Non-patent document 4 discloses a method of obtaining 8-cryptomelane interaction of 2,4-diamino-5-triptorelin-6-oxo-1,6-dihydropyrimidine, which is produced by the interaction of 2,4,5-triamino-6-oxo-1,6-dihydropyrimidine and triperoxonane acid, with triperoxonane anhydride. However, all of these methods are not industrially because of mnogostadiinost, including obtaining raw foods.

Regarding direct perftoruglerodnye these nucleic bases, for example, Patent document 4 discloses a method of producing purines having performanceline group in the 8-position or 2-position, the interaction of purines with N,O-bis(trimethylsilyl)trifurcation in the presence of pyridine and trimethylchlorosilane as catalysts, followed by the interaction of the compounds with bis(perfluoroalkyl) peroxide. However, this method has drawbacks, since it uses peroxide, di(halogenated), which makes the industry the military implementation, as used harperperennial solvent and because it forms the regioisomers with the Deputy at various positions.

Non-patent documents 5 and 6 disclose a method of obtaining a 5-performatively, 8-performancelimiting and 8-performancerating salts by electrochemical formation of the anion of uracil, and subsequent interaction with performativity. However, this method has drawbacks, since it uses an electrochemical method, which is industrially difficult and which gives the final product, representing salt as a supporting electrolyte.

Non-patent document 7 discloses a method of obtaining 8-triptorelin interaction 8-triptorelin obtained by the interaction of 5,6-diamino-1,3-dimethyluracil and triperoxonane anhydride with potassium carbonate and methyliodide in N,N-dimethylformamide. However, this method does not include industrial because of mnogostadiinost, including obtaining raw foods.

As for perftoruglerodnye performanceevaluation, non-Patent document 8 discloses a method of producing triftormetilfosfinov the interaction of 2',3',5'-tri-O-acetylated odnoklassnikov with copper powder and triptoreline in hexamethylphosphoric triamide to obtain 2',3'5'-tri-O-acetylated cryptosociology, and subsequent removal of the protection. However, this method also has disadvantages associated with multi-stage and application hexamethylphosphoric triamide, which is difficult for industrial applications.

In addition, non-Patent documents 9 and 10 disclose a method of using performativity or performability, which is liquid at room temperature, by use of dimethyl sulfoxide, hydrogen peroxide and iron sulfate. However, the substrates are limited to pyrrole-indoles and substituted benzenes. In addition, not disclosed description triptoreline application performancerelated, which is at room temperature gas, such as cryptomaterial.

Patent document 1: JP-A-2001-247551

Patent document 2: JP-A-11-246590

Patent document 3: JP-A-6-73023

Non-patent document 1: Journal of Organic Chemistry, Vol. 53, pp. 4582-4585, in 1988

Non-patent document 2: Journal of Medicinal Chemistry, Vol. 13, pp. 151-152, in 1970

Non-patent document 3: Journal of American Chemical Society, Vol. 80, pp. 5744-5752, in 1957

Non-patent document 4: Justus Libigs Annalen der Chemie, Vol. 726, pp. 201-215, in 1969

Patent document 4: JP-A-5-1066

Non-patent document 5: Tetrahedron Letters, Vol. 33, pp. 7351-7354, in 1992

Non-patent document 6: Tetrahedron, Vol. 56, pp. 2655-2664, in 2000

Non-patent document 7: Journal of Medicinal Chemistry, Vol. 36, pp. 2639-2644, in 1993

Non-patent document 8: Journal of Chemical Society,Perkin Transaction 1, pp. 2755-2761, in 1980

Non-patent document 9: Tetrahedron Letters, Vol. 34, No. 23, pp. 3799-3800, in 1993

Non-patent document 10: the Journal of Organic Chemistry, Vol. 62, pp. 7128-7136, in 1997

Disclosure of invention

The object of the invention

The object of the present invention is the provision of a simple and effective method of obtaining a nucleic base, having performanceline group.

Means for accomplishing the object of the invention

In order to achieve the above object of the invention were conducted intensive and extensive studies and as a result it was found that the nucleic acid may be performancedriven in one stage, performanceevaluation in the presence of a sulfoxide, peroxide and compounds of iron, thus providing a very simple obtaining nucleic bases with performanceline group that determines the present invention.

Namely, the present invention includes the following aspects:

1. A method of obtaining a nucleic base, having performanceline group, comprising the reaction of nucleic bases with performancingads represented by the General formula (2)

where Rf represents a C1-C6performanceline group, and X represents a halogen atom, in the presence of a sulfoxide represented by the General forms of the Loy (1)

where each of R1aand R1brepresents a C1-C12alkyl group or optionally substituted phenyl group, peroxide and compounds of iron.

2. The method in accordance with the above aspect 1, where the reaction is carried out in the presence of acid.

3. The method in accordance with the above aspect 1 or 2, where the nucleic bases are orally represented by the General formula (3)

where R2represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R3represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and R4represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted C1-C4alkoxygroup, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; cytosine represented by the General formula (4)

where R5represents a hydrogen atom, optionally substituted C 1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R6represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; and each of R7and R8represents a hydrogen atom or a protective group for nitrogen; adenine represented by the General formula (5)

where R9represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R10represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; and each of R11and R12represents a hydrogen atom or a protective group for nitrogen; guanine represented by the General formula (6)

where R13represents a hydrogen atom, optionally substituted C1-C6Alki is inuu group or a protective group for the nitrogen, R14represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and each of R15and R16represents a hydrogen atom or a protective group for the nitrogen; the connection gipoksantina represented by the General formula (7)

where R17represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for the nitrogen, and R18represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues; or xantina represented by the General formula (8)

where R19represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R20represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and R21represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for the nitrogen.

4. The method in accordance with the above aspect 3, where the nucleic base before the hat is orally, represented by the General formula (3)

where R2, R3and R4are the same as defined above.

5. The method in accordance with any of the above aspects 1 to 4, where X represents iodine or bromine.

6. The method in accordance with any of the above aspects 1 to 5, where Rf represents triptorelin group or perforation group.

7. The method in accordance with any of the above aspects 1 to 6, where the composition of iron is a ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide, iodide of iron, iron acetate, iron oxalate, bis(acetylacetonate)iron, ferrocene, bis(η5-pentamethylcyclopentadienyl)iron or iron powder.

8. The method in accordance with the above aspect 7, where the composition of iron is a ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, ferrocene or iron powder.

9. The method in accordance with any of the above aspects 1 to 8, wherein the peroxide is hydrogen peroxide, the composite hydrogen peroxide-urea, tert-butyl peroxide or peroxidase acid.

10. The method in accordance with the above aspect 9, where the peroxide is hydrogen peroxide or a composite hydrogen peroxide-machev is on.

11. The method in accordance with any of the above aspects from 2 to 10, where acid is a sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetracarbonyl acid, formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid or triperoxonane acid.

12. The method in accordance with the above aspect 11, where the acid is a sulfuric acid, tetracarbonyl acid or triftormetilfullerenov acid.

13. The method in accordance with any of the above aspects 1 to 12, where each of R1aand R1brepresents a methyl group, boutelou group or phenyl group.

14. The method in accordance with any of the above aspects 1 to 13, where the reaction temperature is from 20 to 100°C.

15. The method in accordance with any of the above aspects 1 to 14, where the reaction is carried out at a pressure from atmospheric pressure (0.1 MPa) to 1.0 MPa.

16. 5-Performquery represented by the General formula (9)

where Rf represents a C1-C6performanceline group, each of R22and R23represents a hydrogen atom or optionally substituted 1-C6alkyl group, and R24represents an optionally substituted C1-C6alkyl group, optionally substituted by an amino group or optionally substituted C2-C5alkoxycarbonyl group; provided that when each of R22and R23represents a hydrogen atom, R24represents an optionally substituted C2-C5alkoxycarbonyl group.

17. 8-Performancecenter represented by the General formula (10)

where Rf represents a C1-C6performanceline group and each of R25, R26and R27represents a hydrogen atom or optionally substituted C1-C6alkyl group, provided that R25, R26and R27all together are not a hydrogen atom.

The effectiveness of the invention

The present invention provides a high yield economical obtaining nucleic bases with performanceline group, which is a useful compound as a drug or intermediate compounds for medical and agricultural chemicals.

The best way of carrying out the invention

Further, the present invention will be described in detail in detail.

Each isoclinic grounds as the crude product and nucleic acid base, having performanceline group as the product of the present invention may be a mixture of tautomers, such as keto-form and enol form and the present invention includes tautomers. For the purpose of convenience in the description and claims of the present description presents the keto-form.

Concrete examples of C1-C12the alkyl group denoted by each of R1aand R1binclude methyl group, ethyl group, through the group, isopropyl group, cyclopropyl group, boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, cyclobutyl group, cyclopropylmethyl group, dodecyloxy group and so on. Specific examples of optionally substituted phenyl groups, designated as each of R1aand R1binclude phenyl group, p-taillow group, m-taillow group, o-taillow group and so on. Each of R1aand R1bpreferably represents a methyl group, boutelou group, dodecyloxy group, phenyl group or p-taillow group and more preferably a methyl group, boutelou group or a phenyl group from the viewpoint of good yield.

Concrete examples of C1-C6perforaciones group, denoted as Rf, include triptorelin group, perforation group, perft bromilow group, performapply group, partticularly group, performatrin group, perversonality group, PERFLUORO-sec-boutelou group, PERFLUORO-tert-boutelou group, perftortoluol group, perforcerepository group, performanceline group, PERFLUORO-1,1-dimethylpropylene group, PERFLUORO-1,2-dimethylpropylene group, peritoneovenous group, PERFLUORO-1-methylbutyl group, PERFLUORO-2-methylbutyl group, PERFLUORO-3-methylbutyl group, perperikonfortunately group, PERFLUORO-2-cyclopropylamino group, perftorsilanami group, performanceline group, PERFLUORO-1-methylpentyl group, PERFLUORO-2-methylpentyl group, PERFLUORO-3-methylpentyl group, performtheir group, PERFLUORO-1,1-dimethylbutyl group, PERFLUORO-1,2-dimethylbutyl group, PERFLUORO-2,2-dimethylbutyl group, PERFLUORO-1,3-dimethylbutyl group, PERFLUORO-2,3-dimethylbutyl group, PERFLUORO-3,3-dimethylbutyl group, PERFLUORO-1-ethylbutyl group, PERFLUORO-2-ethylbutyl group, PERFLUORO-1,1,2-trimethylpropyl group, PERFLUORO-1,2,2-trimethylpropyl group, PERFLUORO-1-ethyl-1-methylpropyloxy group, PERFLUORO-1-ethyl-2-methylpropyloxy group, perftorirovannogo group and so on.

From the viewpoint of a good implementation as a medical drug among the STV and good product yield, Rf preferably represents triptorelin group, perforation group, perferrably group, performapply group, performatrin group, perversonality group, PERFLUORO-sec-boutelou group, PERFLUORO-tert-boutelou group or performanceline group, more preferably triptorelin group or perforation group.

X represents a halogen atom, and specific examples include a fluorine atom, chlorine atom, bromine atom and iodine atom. From the viewpoint of good yield, X preferably represents an iodine atom or a bromine atom, and more preferably an iodine atom.

Examples of nucleic bases in the present invention include orally, pseudorutile, timiny, cytosine, adenine, guanine, hypoxanthine and xantina, whose basic structure represented by formula (N-1) to (N-8) respectively in table 1.

TABLE 1

Of these nucleic bases preferably represent orally, cytosine, adenine, guanine, hypoxanthine or xantina represented by the General formulas from (3) to (8), respectively, and particularly preferably orally, who expressed General formula (3) among other terms of good implementation of the process of obtaining medical drugs.

where R2represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R3represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R4represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted C1-C4alkoxygroup, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; R5represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R6represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxide onilne group; each of R7and R8represents a hydrogen atom or a protective group for a nitrogen, R9represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R10represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; each of R11and R12represents a hydrogen atom or a protective group for a nitrogen, R13represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R14represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, each of R15and R16represents a hydrogen atom or a protective group for a nitrogen, R17represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R18represents a hydrogen atom, optionally substituted C1-C6alkyl group, protective the th group for nitrogen, or one of pentony residues and their analogues, R19represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R20represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues and R21represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for the nitrogen.

Specific examples of optionally substituted C1-C6the alkyl group denoted by each of R2and R3in the General formula (3)include methyl group, ethyl group, through the group, isopropyl group, cyclopropyl group, boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, cyclobutyl group, cyclopropylmethyl group, pentelow group, neopentylene group, hexoloy group, tsiklogeksilnogo group and so on. In addition, each of these alkyl groups may be substituted by a halogen atom, and specific examples of substituted alkyl groups include chloromethylene group, 2-chloraniline group, 3-chloropropylene group, deformational group, 3-forproperty group, triptorelin group, 2-foretelling group, 2,2,2-triptorelin group, 2,2,2-trichlorethylene gruppi so on.

Specific examples of the protective group for the nitrogen atom marked each of R2and R3include acetyl group, propionyl group, pivaloyloxy group, propargyl group, benzoyloxy group, p-phenylbenzyl group, benzyl group, p-methoxybenzyloxy group, trityloxy group, 4,4'-dimethoxytrityl group, methoxyethoxymethyl group, phenoxycarbonyl group, benzyloxycarbonyl group, tert-butoxycarbonyl group, 9-fluorenylmethoxycarbonyl group, allyl group, n-metoksifenilny group, trifluoracetyl group, methoxymethyl group, 2-(trimethylsilyl)ethoxymethyl group, allyloxycarbonyl group, trichlorocarbanilide group and so on.

R2preferably represents a hydrogen atom or methyl group from the viewpoint of good yield.

Specific examples pentony residues and their analogs, designated as R3include formulae (P-1) to (P-401), are presented in tables 2-16. It should be noted that in formulas (P-1) (P-401) the shaded circle represents a nitrogen atom that is attached to the nucleic acid base, Me represents methyl group, Et represents an ethyl group, Pr represents a sawn groupiPr represents isopropyl gr the PPU, Bu is boutelou grouptBu represents a tert-boutelou group, Ph represents a phenyl group, TMS represents trimethylsilyl group, TBDPS represents a tert-butyldiphenylsilyl group, and Ts represents tonilou group.

In addition, the free hydroxyl group in pentose residue may be protected by a conventional protecting group, such as benzoline group, p-chlorbenzoyl group, toluylene group, benzyl group, tert-butylcellosolve group, tert-butyldimethylsilyl group, acetyl group, mesyl group, benzyloxycarbonyl group, tert-butyldiphenylsilyl group, trimethylsilyl group, Casilina group, tert-butylcellosolve group, p-methoxyphenylalanine group, p-monomethoxypolyethylene group, di(p-methoxy)triticina group, p-chlorophenylalanine group, m-triftormetilfullerenov group, pivellina group, (9-fluorenyl)methoxycarbonyl group (biphenyl-4-yl)carbonyl group, formyl group, (2-naphthyl)carbonyl group, tert-butyldimethylsilyl group, triisopropylsilyl group, Tripropylamine group, triphenylmethyl group, butylcellosolve group, acylcarnitine group, propellerblade group, monicamonica group or p-metoksifenilny group.

In addition, when hydroxyl groups are both in the 2'-position and 3'-position, they may be secured together isopropylidene group or the like, with the formation of rings. In addition, the free amino group may be protected by a conventional protecting group, such as triftormetilfullerenov group, 2,4-dinitroaniline group, Casilina group, acetyl group, benzyloxycarbonyl group, triphenylmethyl group, benzoline group, benzyl group, adamantylidene group, butylcellosolve group, calolina group or tetrabromophthalimide group. In addition, free mercaptopropyl may be protected by a conventional protecting group such as 2,4,6-triisopropylphenyl group, benzoline group, benzyl group or acetyl group.

TABLE 2

TABLE 3

TABLE 4

TABLE 5

TABLE 6

TABLE 7

TABLE 8

TABLE 9

TABLE 10

TABLE 11

TABLE 12

TABLE 13

TABLE 14

TABLE 15

TABLE 16

3preferably represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6alkyl groups designated as R4in the General formula (3)include optionally substituted C1-C6alkyl groups disclosed in the description for R2.

Specific examples of optionally substituted C1-C4alkoxygroup include a methoxy group, ethoxypropan, propoxylate, isopropylacetate, cyclopropylamino, butoxypropyl, isobutylacetate, sec-butylacrylate, tert-butylacrylate, cyclobutylamine, cyclopropylmethoxy and so on. In addition, each of these alkoxygroup may be substituted by a halogen atom, and specific examples include chlorotoxin, 2-chlorethoxyfos, 3-chloropropoxy, dipterocarp, 3-forproposals, cryptometer, 2-floridacheap, 2,2,2-triptracker, 2,2,2-trichlorethene and so on.

Examples of the optionally substituted amino group, designated as R4include an amino group which may be substituted C1-C4alkyl gr is POI and its specific examples include amino group, methylaminopropyl, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, N,N-dimethylaminopropyl, N,N-diethylaminopropyl, N,N-dipropylamino, N,N-diisopropylamino, N,N-dibutylamino, N,N-diisobutylamine, N,N-di-sec-butylamino, N,N-di-tert-butylamino and so on.

In addition, the amino group may be substituted by a protective group for the nitrogen and specific examples of substituted amino groups include acetylamino, propionamido, evaluieringsrapport, propargylamine, benzoylamino, p-phenylbenzophenone, benzylamine, p-methoxybenzylamine, titilating, 4,4'-dimethoxytrityl, methoxyethoxymethyl, phenoxycarbonylamino, benzyloxycarbonylamino, tert-butoxycarbonylamino, 9-fluorenylmethoxycarbonyloxy, allelomorph, p-methoxyphenylalanine, triptoreline, methoxyethylamine, 2-(trimethylsilyl)ethoxymethylene, allyloxycarbonyl, trichlorocarbanilide and so on.

Example optionally substituted carbamoyl groups designated as R4includes carbamoyl group which may be substituted C1-C4alkyl the Oh group on the nitrogen atom, and specific examples include karbamoilnuyu group, N-methylcarbamoyl group, N-ethylcarbazole group, N-profilirovannuju group, N-isopropylcarbamate group, N-butylcarbamoyl group, N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group, N,N-dipropylamino group, N,N-diisopropylcarbodiimide group, N,N-dibutylamino group and so on.

Specific examples of optionally substituted C2-C5alkoxycarbonyl groups designated as R4include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butyloxycarbonyl group, isobutylacetophenone group, sec-butyloxycarbonyl group, tert-butyloxycarbonyl group and so on. In addition, each of these alkoxycarbonyl groups may be substituted by a halogen atom, and specific examples of substituted alkoxycarbonyl groups include 2-chlorocarbonates group, 3-chloropropionitrile group, deformationally group, 3-ferroelectronics group, triphtalocyaninine group, 2-forecastable group, 2,2,2-triftoratsetofenona group, 2,2,2-trichlorocarbanilide group and so on.

R4preferably represents a hydrogen atom, 2-chloraniline group, amino group, tert-butox is carbonylation or carboxyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R5in the General formula (4)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R5include protective group for the nitrogen disclosed in the description for R2. Specific examples pentony residues and their analogues, denoted by R5including from (P-1) to (P-401), disclosed in the description of R3. R5preferably represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6alkyl groups designated as R6in the General formula (4)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the optionally substituted amino group, designated as R6include optionally substituted amino group disclosed in the description for R4. Specific examples of optionally substituted carbamoyl groups designated as R6include optional substituted to ramornie group, disclosed in the description for R4. Specific examples of optionally substituted C2-C5alkoxycarbonyl groups designated as R6include optionally substituted C2-C5alkoxycarbonyl group disclosed in the description for R4. Preferably R6represents a hydrogen atom, 2-chloraniline group, amino group, tert-butoxycarbonylamino or carboxyl group from the viewpoint of good yield.

Specific examples of the protective group for the nitrogen designated as each of R7and R8in the General formula (4)include a protective group for the nitrogen disclosed in the description for R2. Each of R7and R8preferably represents a hydrogen atom or acetyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R9in the General formula (5)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R9include protective group for the nitrogen disclosed in the description for R2. Specific examples pentony residues and their analogues, denoted by R9including from (P-1) to (P-401), disclosed in the description of R3. R9 preferably represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6alkyl groups designated as R10in the General formula (5)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the optionally substituted amino group, designated as R10include optionally substituted amino group disclosed in the description for R4. Specific examples of optionally substituted carbamoyl groups designated as R10include optionally substituted carbamoyl group disclosed in the description for R4. Specific examples of optionally substituted C2-C5alkoxycarbonyl groups designated as R10include optionally substituted C2-C5alkoxycarbonyl group disclosed in the description for R4. Preferably R10represents a hydrogen atom, 2-chloraniline group, amino group, tert-butoxycarbonylamino or carboxyl group from the viewpoint of good yield.

Specific examples of the protection is based groups for nitrogen, designated as each of R11and R12in the General formula (5)include a protective group for the nitrogen disclosed in the description for R2. Each of R11and R12preferably represents a hydrogen atom or acetyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R13in the General formula (6)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R13include protective group for the nitrogen disclosed in the description for R2. R13preferably represents a hydrogen atom or methyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R14in the General formula (6)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R14include protective group for the nitrogen disclosed in the description for R2. Specific examples pentony residues and their analogues, denoted by R14including from (P-1) to (P-401), disclosed in the description of R3. Predpochtitel what about the R 14represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical lekarstvennogo tools or agricultural chemical, or an intermediate connection.

Specific examples of the protective group for the nitrogen designated as each of R15and R16in the General formula (6)include a protective group for the nitrogen disclosed in the description for R2. Each of R15and R16preferably represents a hydrogen atom or acetyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R17in the General formula (7)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R17include protective group for the nitrogen disclosed in the description for R2. Preferably R17represents a hydrogen atom or methyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R18in the General formula (7)include optionally substituted C1-C6alkyl group, rusk is ytie in the description for R 2. Specific examples of the protective group for the nitrogen, denoted as R18include protective group for the nitrogen disclosed in the description for R2. Specific examples pentony residues and their analogues, denoted by R18including from (P-1) to (P-401), disclosed in the description of R3. Preferably R18represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6alkyl groups designated as R19in the General formula (8)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R19include protective group for the nitrogen disclosed in the description for R2. Preferably R19represents a hydrogen atom or methyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6alkyl groups designated as R20in the General formula (8)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of protection of the Noah group for nitrogen, designated as R20include protective group for the nitrogen disclosed in the description for R2. Specific examples pentony residues and their analogues, denoted by R20including from (P-1) to (P-401), disclosed in the description of R3. Preferably R20represents a hydrogen atom, methyl group, (P-34), (P-35), (P-75), (P-100), (P-101), (P-123), (P-152), (P-153), (P-314) or (P-315) from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6alkyl groups designated as R21in the General formula (8)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the protective group for the nitrogen, denoted as R21include protective group for the nitrogen disclosed in the description for R2. Preferably R21represents a hydrogen atom or methyl group from the viewpoint of good yield.

Specific examples of optionally substituted C1-C6the alkyl group denoted by each of R22or R23in the General formula (9)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Each of R22and R23can be any of the Ala is through groups, described above, and preferably represents a methyl group or ethyl group from the point of view of the expected physiological activity. Specific examples of optionally substituted C1-C6alkyl groups designated as R24in the General formula (9)include optionally substituted C1-C6alkyl groups disclosed in the description for R2. Specific examples of the optionally substituted amino group, designated as R24include optionally substituted amino group disclosed in the description for R4. Specific examples of optionally substituted C2-C5alkoxycarbonyl groups designated as R24include optionally substituted C2-C5alkoxycarbonyl group disclosed in the description for R4. Preferably R24represents a methyl group, ethyl group, amino group or the amino group, substituted by a protective group from the point of view of useful life as a medical or agricultural chemical, or an intermediate connection.

Specific examples of optionally substituted C1-C6the alkyl group denoted by each of R25, R26and R27in the General formula (10)include optionally substituted C1-C6alkyl groups disclosed in the description of the AI for R 2. Each of R25, R26and R27preferably represents a methyl group or ethyl group from the point of view of the expected functioning to obtain a stable output.

Next will be described the method of obtaining of the present invention.

For the case when the use orally General formula (3) as the source, presents a method of obtaining [Method A], and thus receive 5-performquery represented by the General formula (11).

[Method A]

where R2, R3, R4, Rf and X are the same as described above.

[Method a] sulfoxidov (1) can be used as such as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. The solvent preferably is a water, sulfoxidov (1) or solvent is, consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio of orallow (3) and sulfoxide (1) is preferably from 1:1 to 1:200 and more preferably from 1:10 to 1:100 from the viewpoint of good yield.

The molar ratio of orallow (3) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide or composite hydrogen peroxide-urea from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use a hydrogen peroxide concentration of 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio of orallow (3) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield prod the KTA.

Connection, iron preferably is a salt of iron from the viewpoint of good yield and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron, ferrocene and bis(η5-pentamethylcyclopentadienyl)iron and they can be used acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II) in the system. In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, ferrocene or iron powder from the viewpoint of good yield.

These iron compounds can be used as such in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and the water is before occhialini among them. In this case, the concentration of the solution of iron compounds is preferably from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/l from the viewpoint of good yield.

The molar ratio of orallow (3) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction is carried out in a closed system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) the composition is scored from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this case, the pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction is effective even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 ml/min, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane the acid. They can be used acceptable in combination. It is preferable to use sulfuric acid, terraforming acid or triftormetilfullerenov acid from the viewpoint of good yield.

In addition, there may be used an acid salt of sulfuric acid. Examples of acid salts include hydrosulphate of Tetramethylammonium, hydrosulphate of tetraethylammonium, tetrabutylammonium hydrosulfate, hydrosulfate tetraphenylporphine and so on.

These acids may be used after dilution. The solvent in this case can be selected from sulfoxidov (1) and the solvents described above, and water, sulfoxide compounds (1) or solvent mixtures of water and sulfoxide compounds (1), which predpochtitelnei among them.

The molar ratio of orallow (3) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the viewpoint of good yield.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction and the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

For having the best, when cytosine General formula (4) is used as the source, below is a way to obtain as [Method B], and you get a 5-performancesin represented by the General formula (12).

[Method B]

where R5, R6, R7, R8, Rf and X are the same as described above.

[Method B], sulfoxidov (1) as such can be used as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. The solvent preferably is a water, sulfoxidov (1) or a solvent consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio of cytosine (4) and sulfoxidov (1) is preferably from 1:1 to 1:200 and more preferably from 1:10 to 1:100 from the viewpoint of good yield.

Molar with the compared of cytosines (4) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use a hydrogen peroxide concentration of 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio of cytosine (4) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield.

Connection, iron preferably is a salt of iron(II) from the viewpoint of good yield and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene and bis(η5-pentamethylcyclopentadienyl)iron and they can be IP is alsomany acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II). In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate from the viewpoint of good yield.

These iron compounds can be used as such in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and water is preferable among them. In this case, the concentration of the solution of iron compounds is preferably from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/L.

The molar ratio of cytosine (4) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction is carried out in closed the th system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) is from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this case, the pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction is effective even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 mlmin, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia acid and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane acid. They can be used acceptable in combination. It is preferable to use sulfuric acid from the viewpoint of good yield.

These acids may be used after dilution. The solvent in this case can be selected from sulfoxidov (1) and the solvents described above, as well as water, sulfoxidov (1) or solvent mixtures of water and sulfoxidov (1), which predpochtitelnei among them.

The molar ratio of cytosine (4) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the viewpoint of good yield PR the product.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction and the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

For the case when adenine General formula (5) is used as the source, below is a way to obtain as [Method C] and 8-perftoruglerodnye represented by the General formula (13).

[Method C]

where R9, R10, R11, R12, Rf and X are the same as described above.

[Method C] sulfoxidov (1) as such can be used as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. actuarial preferably represents water, the sulfoxidov (1) or a solvent consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio of adenine (5) and sulfoxidov (1) is preferably from 1:1 to 1:200 and more preferably from 1:10 to 1:100 from the viewpoint of good yield.

The molar ratio of adenine (5) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use a hydrogen peroxide concentration of 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio of adenine (5) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield.

Connection, iron preferably is a salt of iron(II) from the viewpoint of good yield and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene and bis(η5-pentamethylcyclopentadienyl)iron and they can be used acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II). In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate from the viewpoint of good yield.

These iron compounds can be used as such in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and water is preferable among them. In this case, the concentration of the solution of iron compounds preference is sustained fashion ranges from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/L.

The molar ratio of adenine (5) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction is carried out in a closed system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) is from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this text the tea pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction effectively takes place even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 ml/min, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane acid. They can be used acceptable in combination. It is preferable to use sulfuric acid from the viewpoint of good yield.

These acids may be used after dilution. The solvent in this case may be the pre-selected from sulfoxidov (1) and solvents, described above, as well as water, sulfoxidov (1) or solvent mixtures of water and sulfoxidov (1), which predpochtitelnei among them.

The molar ratio of adenine (5) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the viewpoint of good yield.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction and the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

For the case where the guanine General formula (6) is used as the source, below is a way to obtain as [Method D] and 8-perforaciones represented by the General formula (14).

[Method D]

where R13, R14, R15, R16, Rf and X are the same as described above.

[Method D] sulfoxidov (1) as such can be used as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, Tetra is hydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. The solvent preferably is a water, sulfoxidov (1) or a solvent consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio of guanine (6) and sulfoxidov (1) is preferably from 1:1 to 1:5000 and more preferably from 1:10 to 1:3000 with the viewpoint of good yield.

The molar ratio of guanine (6) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use the concentration of the hydrogen peroxide 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio of guanine (6) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield.

Connection, iron preferably is a salt of iron(II) from the viewpoint of good yield and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene and bis(η5-pentamethylcyclopentadienyl)iron, and they can be used acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II). In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate from the viewpoint of good yield.

These iron compounds can be used as the new in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and water is preferable among them. In this case, the concentration of the solution of iron compounds is preferably from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/L.

The molar ratio of guanine (6) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction is carried out in a closed system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state is AI. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) is from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this case, the pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction is effective even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 ml/min, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia Isleta, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane acid. They can be used acceptable in combination. It is preferable to use sulfuric acid from the viewpoint of good yield.

These acids may be used after dilution. The solvent in this case can be selected from sulfoxidov (1) and the solvents described above, as well as water, sulfoxidov (1) or solvent mixtures of water and sulfoxidov (1), which predpochtitelnei among them.

The molar ratio of guanine (6) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the viewpoint of good yield.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction and the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

For the case when hypoxanthine General formula (7) is used as the source, below is a way to obtain as [Method E] and 8-PERFLUORO lilypadmartinez, represented by the General formula (15).

[Method E]

where R17, R18, Rf and X are the same as described above.

[Method E] sulfoxidov (1) as such can be used as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. The solvent preferably is a water, sulfoxidov (1) or a solvent consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio of hypoxanthine (7) and sulfoxidov (1) is preferably from 1:1 to 1:200 and more preferably from 1:10 to 1:100 from the viewpoint of good yield.

The molar ratio of hypoxanthine (7) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

<> Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use a hydrogen peroxide concentration of 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio of hypoxanthine (7) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield.

Connection, iron preferably is a salt of iron(II) from the viewpoint of good yield, and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene and bis(η5-pentamethylcyclopentadienyl)iron, and they can be used too acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II). In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate or ferrocene from the viewpoint of good yield.

These iron compounds can be used as such in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and water is preferable among them. In this case, the concentration of the solution of iron compounds is preferably from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/L.

The molar ratio of hypoxanthine (7) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction p is avodat in a closed system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) is from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this case, the pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction is effective even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 mlmin, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane acid. They can be used acceptable in combination. It is preferable to use sulfuric acid from the viewpoint of good yield.

These acids may be used after dilution. The solvent in this case can be selected from sulfoxidov (1) and the solvents described above, as well as water, sulfoxidov (1) or solvent mixtures of water and sulfoxidov (1), which predpochtitelnei among them.

The molar ratio of hypoxanthine (7) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the point of view of the good output is a product.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction and the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

For the case when xantina General formula (8) is used as the source, below is a way to obtain as [Method F] and 8-performancecenter represented by the General formula (16).

[Method F]

where R19, R20, R21, Rf and X are the same as described above.

[Method F] sulfoxidov (1) as such can be used as a solvent, but it is also possible to use a solvent which does not adversely affect the course of the reaction. Specific examples of solvents include water, N,N-dimethylformamide, acetic acid, triperoxonane acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4 dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl alcohol, triptorelin, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N,N,N',N'-tetramethylrhodamine, N,N'-dimethylpropyleneurea and so forth, and they are acceptable can be used in combination. The solution is tel preferably represents water, the sulfoxidov (1) or a solvent consisting of a mixture of water and sulfoxidov (1) from the viewpoint of good yield.

The molar ratio xantina (8) and sulfoxidov (1) is preferably from 1:1 to 1:5000 and more preferably from 1:10 to 1:1000 from the viewpoint of good yield.

The molar ratio xantina (8) and performanceevaluation (2) is preferably from 1:1 to 1:100 and more preferably from 1:1.5 to 1:10 from the viewpoint of good yield.

Examples of peroxides include hydrogen peroxide, composite hydrogen peroxide-urea, tert-butyl peroxide, peroxyoctanoic acid and so forth, and they can be used acceptable in combination. Peroxide preferably represents hydrogen peroxide from the viewpoint of good yield.

Hydrogen peroxide can be used after diluting it with water. In this case, the concentration can range from 3 to 70% by weight, but commercially it is permissible to use a hydrogen peroxide concentration of 35% by weight. More preferred is the dilution of the hydrogen peroxide water for 10 to 30 mass% from the viewpoint of good yield and security.

The molar ratio xantina (8) and peroxides is preferably from 1:0.1 to 1:10 and more preferably from 1:1.5 to 1:3 from the viewpoint of good yield.

Connection, iron preferably is a salt of iron(II) from the viewpoint of good yield and its examples include inorganic salts such as ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, iron chloride, iron bromide and iodide of iron, and ORGANOMETALLIC compounds such as iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene and bis(η5-pentamethylcyclopentadienyl)iron, and they can be used acceptable in combination. Additionally, there may be used a powder of iron, a compound of iron(0) or iron salts(I) in combination with chemical oxidation, such as peroxide, in order to generate a salt of iron(II). In this case, the hydrogen peroxide used in the reaction, can also be used as a reagent for the oxidation of as such. The connection is preferably iron is a ferrous sulfate, tetrafluoroborate iron, ferrocene or iron powder from the viewpoint of good yield.

These iron compounds can be used as such in the solid state, but they can also be used in the form of a solution. When used in the form of a solution, the solvent used may be any of the sulfoxidov (1) and the solvents described above, and water is preferable among them. With the learn the solution concentration of iron compounds is preferably from 0.1 to 10 mol/l and more preferably from 0.5 to 5 mol/L.

The molar ratio xantina (8) and iron compounds is preferably from 1:0.01 to 1:10 and more preferably from 1:0.1 to 1:1 from the viewpoint of good yield.

The reaction can be carried out at a temperature, optionally selected in the range from 20 to 100°C. the temperature Interval is preferably from 20 to 70°C from the viewpoint of good yield.

When the reaction is carried out in a closed system, the reaction can be conducted under pressure, optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, and the reaction effectively takes place even at atmospheric pressure. In addition, the surrounding atmosphere when carrying out the reaction may be an inert gas, such as argon or nitrogen, the reaction effectively takes place even in an atmosphere of air.

When performancerelated General formula (2) is a gas at room temperature, they can be used as such in the gaseous state. In this case, they can be applied in the form of the gas mixture after dilution gas, such as argon, nitrogen, air, helium or oxygen, where the molar fraction of performanceevaluation (2) is from 1 to 100%. When the reaction is carried out in a closed system, performancerelated (2) or gas mixture can be used as the reaction atmosphere. In this text the tea pressure can be optionally selected in the range from atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction effectively takes place even at atmospheric pressure. On the other hand, performancerelated (2) or gas mixture in an open system can be introduced into the reaction solution by borbatirovaniya. In this case, enter the value of performanceevaluation (2) or gas mixture can be selected in the range from 1 to 200 ml/min, although this choice depends on the level of reaction, amount of catalyst, the temperature of the reaction mixture and the molar fraction of performanceevaluation (2) in the gas mixture.

In accordance with the method of the present invention, the yield of the desired product can be increased by adding acid. Examples of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetraberlinia acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid and triperoxonane acid. They can be used acceptable in combination. It is preferable to use sulfuric acid or terraforming acid from the viewpoint of good yield.

These acids may be used after dilution. Dissolve the fir in this case can be selected from sulfoxidov (1) and solvents, described above, as well as water, sulfoxidov (1) or solvent mixtures of water and sulfoxide compounds (1), which is preferred among them.

The molar ratio xantina (8) and acid is preferably from 1:0.001 to 1:5 and more preferably from 1:0.01 to 1:2 from the viewpoint of good yield.

There are no particular restrictions on the method of separating the desired product from the solution after the reaction, the desired product can be obtained by one of the usual methods, such as extraction solvent, chromatography on a column, preparative thin-layer chromatography, preparative liquid chromatography, recrystallization and sublimation.

The compounds obtained according to the production method, described above, 5-performquery represented by the General formula (9), and 8-performancecenter represented by the General formula (10)are new compounds and intend to be used as medical drugs or intermediates for medical and agricultural chemicals.

EXAMPLES

Further, the present invention will be described in detail with reference to examples, but it should be clear that the present invention is by no means the case is not limited to these examples.

EXAMPLE 1

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 94%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Cryptomaterial get in a solid white color (0.17 g, yield: 93%) using preparative thin-layer chromatography.

1H-NMR (deuterated acetone): δ of 8.09 (s, 1H), 10,5 (users, 2H).

13C-NMR (deuterated acetone): δ 104,0 (sq, s, JCF=32,4 Hz), 123,6 (sq, s, JCF=268,2 Hz), 144,2 (sq, s, JCF=5,9 Hz), 150,9, 160,2.

19F-NMR (deuterated acetone): δ-64,1.

MS (m/z): 180[M]+.

EXAMPLE 2

The formation of 5-cryptomaterial (19F-NMR yield: 80%) confirmed in accordance with a technique similar to the method presented in example 1, except that 1.0 mol/l aqueous solution of sulfate is ammonia used instead of 1.0 mol/l aqueous solution of ferric sulfate.

EXAMPLE 3

0.11 g (1.0 mmol) of Uracil and 0,028 g (0.5 mmol) of iron powder are weighed and placed in a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 32%) confirm in accordance with a technique similar to the method presented in example 1.

EXAMPLE 4

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: of 0.21 ml of a 42% aqueous solution terraforming acid, 2.0 ml of dimethylsulfoxide, 3.0 ml of 2.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of tetrafluoroborate iron and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to on the th temperature. The formation of 5-cryptomaterial (19F-NMR yield: 94%) confirmed in accordance with a technique similar to the method presented in example 1.

EXAMPLE 5

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethylsulfoxide, 3.0 ml of 2.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.12 g composite of the hydrogen peroxide-urea and 0.3 ml of 1 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 70%) confirmed in accordance with a technique similar to the method presented in example 1.

EXAMPLE 6

The formation of 5-cryptomaterial (19F-NMR yield: 38%) confirm exactly in accordance with the method similar to the method presented in example 1, except that dimethyl sulfoxide is used instead of 1H. sulfuric acid solution in dimethyl sulfoxide.

EXAMPLE 7

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask for escaut cryptomaterial. Then in the specified flask add the following products: 5,0 ml dibutylsebacate, 0,053 ml of concentrated sulfuric acid, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR output: 0,2%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 8

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced by cryptomaterial. Then in the specified flask add the following products: 5.0 g of diphenylsulfone, 0,053 ml of concentrated sulfuric acid, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR output: 0,5%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 9

The formation of 5-cryptomaterial (19F-NMR yield: 76%) confirm exactly in accordance with methods similar to the methods of the e, in Example 1, except that the reaction is carried out in an atmosphere of air without replacement with argon.

EXAMPLE 10

1.1 g (10 mmol) of Uracil weighed and placed into a 2-necked flask of 100 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following ingredients: 20 ml of 1N. solution of sulfuric acid in dimethyl sulfoxide, 22.5 ml of dimethyl sulfoxide, 7.5 ml of 2.0 mol/l solution of triptoreline in dimethyl sulfoxide, 2.0 ml of 30% aqueous hydrogen peroxide solution and 3.0 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 30 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 94%) confirmed in accordance with a technique similar to the method presented in example 1.

EXAMPLE 11

1.1 g (10 mmol) of Uracil weighed and placed into a 2-necked flask of 100 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: by 0.055 ml of concentrated sulfuric acid, 9 ml of dimethyl sulfoxide, 24.5 mmol of triptoreline, 2.0 ml of 30% aqueous hydrogen peroxide solution and 1.5 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 60 d is 70°C for 10 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 97%) confirm in accordance with a technique similar to the method presented in example 1.

EXAMPLE 12

11.2 g (100 mmol) of Uracil weighed and placed into a 2-necked flask of 300 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 80 ml of dimethyl sulfoxide, with 0.55 ml of concentrated sulfuric acid, 245 mmol of triptoreline, 20 ml of 30% aqueous hydrogen peroxide solution and 10 ml of 1.5 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 60 to 70°C for 100 minutes and then the resulting solution is cooled to room temperature. The formation of 5-cryptomaterial (19F-NMR yield: 97%) confirm in accordance with a technique similar to the method presented in example 1.

EXAMPLE 13

0.11 g (1.0 mmol) of Uracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1,3 ml traducator-1-hodgekin, 1.2 ml of DMSO, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. A mixture of TRANS who mesilat in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-perftorgeksilsilanami (19F-NMR yield: 29%) confirmed19F-NMR with benzotrifluoride as an internal standard. 5-Perftorgeksil get in a solid white color (0,107 g, yield: 25%) using chromatography on a column.

1H-NMR (deuterated chloroform): δ 8,01 (l, JHF=5.7 Hz, 1H), 11,59 (users, 1H), 11,80 (l, JHF=4,8 Hz, 1H).

19F-NMR (deuterated chloroform): δ-126,1 (sq, s, JFF=7,0 Hz, 2F), -122,8 (users, 2F), -122,1 (users, 2F), -121,2 (users, 2F), -108,5 (m, 2F), -80,5 (t, JFF=9.5 Hz, 3F)

MS (m/z): 430[M]+.

EXAMPLE 14

0.18 g (1.0 mmol) of 6-Cryptomaterial and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5,6-bis(trifluoromethyl)uracil (19F-NMR yield: 63%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5,6-is IP(trifluoromethyl)uracil get in a solid white color (0.12 g, yield: 48%) using preparative thin-layer chromatography.

1H-NMR (deuterated acetone): δ of 10.73 (users, 2H).

13C-NMR (deuterated acetone): δ102,5 (sq, s, JCF=32.7 Hz), 120,6 (sq, s, JCF=making up 277.3 Hz), of 123.2 (sq, s, JCF=270,2 Hz), 147,0 (sq, s, JCF=37,0 Hz), shall be 152.3, 161,2.

19F-NMR (deuterated acetone): δ-64,8 (sq, s, JFF=14.6 Hz), -58,4 (sq, s, JFF=14.6 Hz).

MS (m/z): 248[M]+.

EXAMPLE 15

0.17 g (1.0 mmol) of 6-Methoxycarbonylmethyl and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. Education 6-methoxycarbonyl-5-cryptomaterial (19F-NMR yield: 84%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 6-Methoxycarbonyl-5-cryptomaterial get in a solid white color (0.20 g, yield: 80%) using chromatography on Colo is Kyo.

1H-NMR (deuterated acetone): δ of 3.94 (s, 3H), 10,70 (s, 1H), 11,10 (users, 1H).

13C-NMR (deuterated acetone): δ 54,5, 100,8 (square, JCF=32,2 Hz), 123,1 (square, JCF=269,7 Hz), USD 147.4 (square, JCF=3,52 Hz), 149,9, 160,1, 161,6.

19F-NMR (deuterated acetone): δ-60,6.

MS (m/z): 238[M]+.

EXAMPLE 16

0.14 g (1.0 mmol) of 1,3-Dimethyluracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 1,3-dimethyl-5-cryptomaterial (19F-NMR yield: 78%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 1,3-Dimethyl-5-cryptomaterial get in a solid white color (0.12 g, yield: 44%) using preparative thin-layer chromatography.

1H-NMR (deuterated acetone): δ of 3.25 (s, 3H), 3,51 (s, 3H), 8,23 (sq, s, JHF=1,05 Hz, 1H).

13C-NMR (deuterated AC is tone): δ 27,8, 37,6, 102,9 (square, JCF=32,3 Hz), 123,8 (square, JCF=268,4 Hz), 146,4 (square, JCF=5,91 Hz), 151,9, 159,5.

19F-NMR (deuterated acetone): δ-60,6.

MS (m/z): 208[M]+.

EXAMPLE 17

0.16 g (1.0 mmol) 6-Amino-1,3-dimethyluracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 6-amino-1,3-dimethyl-5-cryptomaterial (19F-NMR yield: 95%) confirm19F-NMR with 2,2,2-triptoreline as an internal standard. 6-Amino-1,3-dimethyl-5-cryptomaterial get in a solid white color (0.20 g, yield: 95%) using chromatography on a column.

1H-NMR (deuterated chloroform): δ 3,29 (s, 3H), 3,53 (s, 3H), of 6.20 (s, 2H).

13C-NMR (deuterated chloroform): δ 28,0, 29,7, 80,5 (square, JCF=30,2 Hz), output reached 125.5 (square, JCF=269,1 Hz), 150,4, 153,2, 159,8.

19F-NMR (deuterated chloroform): δ-54,9.

MS m/z: 223[M] +.

EXAMPLE 18

0.26 g (1.0 mmol) of 6-tert-Butoxycarbonylamino-1,3-dimethyluracil weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 6-tert-butoxycarbonylamino-1,3-dimethyl-5-cryptomaterial (19F-NMR yield: 95%) confirm19F-NMR with 2,2,2-triptoreline as an internal standard. 6-tert-Butoxycarbonylamino-1,3-dimethyl-5-cryptomaterial get in a solid white color (0,30 g, yield: 93%) by chromatography on a column.

1H-NMR (deuterated chloroform): δ is 1.51 (s, 9H), of 3.32 (s, 3H), 3.46 in (s, 3H), 6.89 in (users, 1H).

13C-NMR (deuterated chloroform): δ 27,9, 28,5, 32,2, 84,2, 98,4 (square, with JCF=22,8 Hz), 122,8 (sq, s, JCF=to 271.5 Hz), 147,5, 150,6, 151,3, 158,6.

19F-NMR (deuterated chloroform): δ -54,8.

MS (m/z): 250[M-OC4H9]+.

EXAMPLE 19

0.16 g (1.0 mmol) 6-(2-Chloromethyl)uracil and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 6-(2-chloromethyl)-5-cryptomaterial (19F-NMR yield: 55%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 6-(2-chloromethyl)-5-cryptomaterial get in a solid white color (0.10 g, yield: 45%) using preparative thin-layer chromatography.

1H-NMR (deuterated dimethyl sulfoxide): δ4,47(s, 2H), 11,78(users, 1H), 11,82(users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ38,8, 100,9(sq, s, JCF=30,7 Hz), 123,6(sq, s, JCF=270,9 Hz), 150,3, 153,9, 160,9.

19F-NMR (deuterated dimethyl sulfoxide): δ-56,5.

MS (m/z): 228[M]+.

EXAMPLE 20

0.17 g (1.0 mmol) of 6-Carboxymethyl and 0,058 g (0.3 mmol) of ferrocene is weighed and placed in 2-mountains the second flask of 50 ml volume, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 6-carboxy-5-cryptomaterial (19F-NMR yield: 95%) confirm19F-NMR with 2,2,2-triptoreline as an internal standard. 6-Carboxy-5-cryptomaterial get (0,076 g, yield: 34%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 11,71 (users, 1H), 12,13 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 97,2 (square, JCF=31,5 Hz), 122,9 (square, JCF=269,9 Hz), 149,8, 150,3, 160,6, 162,3.

19F-NMR (deuterated dimethyl sulfoxide): δ-58,6.

MS (m/z): 223[M-H]+.

EXAMPLE 21

0.24 g (1.0 mmol) Uridine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following ingredients: 1.5 ml of DMSO, 2 ml of 1N. solution of sulfuric acid in dimethylsulfate the IDA, 1 ml of a 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-triptorelin (19F-NMR yield: 51%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Triptorelin get (0,071 g, yield: 23%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 2,84 (users, 3H), 3,88 (m, 3H), 4,60 (m, 1H), 4,32 (d, J=13,6 Hz, 2H), 4,60 (users, 1H), 5,88 (d, J=13,6 Hz, 1H), 8,88 (s, 1H).

19F-NMR (deuterated dimethyl sulfoxide): δ-61,8.

EXAMPLE 22

of 0.37 g (1.0 mmol) 2',3',5'-Three-O-acetylornithine and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled on the room temperature. The formation of 5-trifluoromethyl-2',3',5'-three-O-acetylornithine (19F-NMR yield: 45%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Trifluoromethyl-2',3',5'-three-O-acetylurea get in a solid white color (0.17 g, yield: 40%) by chromatography on a column.

1H-NMR (deuterated chloroform): δ 2,11 (s, 3H), 2.13 and (s, 3H), and 2.14 (s, 3H), 4,34 (d, J=13,6 Hz, 1H), 4,43 (m, 1H), 4,43 (DD, J=3.2 Hz, to 13.6 Hz, 1H), of 5.34 (t, J=5.4 Hz, 1H), lower than the 5.37 (t, J=5.4 Hz, 1H), 6,07 (d, J=5.4 Hz, 1H), 8,01 (s, 1H), 9,48 (s, 1H).

13C-NMR (deuterated chloroform): δ 20,3, 20,4, 62,7, 69,9, 73,2, 80,5, 87,7, 106,2 (square, JCF=33.3 Hz), to 121.6 (square, JCF=270,3 Hz), 140,2 (square, JCF=6,0 Hz), 149,3, 158,0, 169,6, 169,7, 170,2.

19F-NMR (deuterated chloroform): δ-64,0.

EXAMPLE 23

to 0.23 g (1.0 mmol) of 2'-dose irradiation on neurogenesis is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-reformer-2'-dose irradiation on neurogenesis ( 19F-NMR yield: 85%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Trifluoromethyl-2'-deoxyuridine get in a solid white color (0.17 g, yield: 58%) using chromatography on a column.

1H-NMR (deuterated chloroform): δ 2,35 (DDD, J=6,10 Hz 6.25 Hz, 13,53 Hz, 1H), 2,39 (DDD, J=3,61 Hz 6.25 Hz, 13,53 Hz, 1H), 3,86 (DD, J=11.7 Hz, 15.3 Hz, 2H), was 4.02 (DD, J=3,61 Hz, 6,10 Hz, 1H), 4,46 (users, 2H), 4.53-in (users, 1H), 6,27 (t, J=6.25 Hz, 1H), 8,84 (s, 1H), 10,45 (s, 1H).

13C-NMR (deuterated chloroform): δ 42,0, 62,0, 71,4, 86,9, 89,0, 104,5 (square, JCF=32,4 Hz), 123,7 (square, JCF=268,6 Hz), 143,1 (square, JCF=5,66 Hz), 150,5, 159,4.

19F-NMR (deuterated chloroform): δ-63,7.

EXAMPLE 24

0.32 g (1.0 mmol) of 3',5'-di-O-acetyl-2'-dose irradiation on neurogenesis and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 1.8 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of a 2.1 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-trifluoromethyl-3',5'-di-O-acetyl-2'-ethoxyaniline ( 19F-NMR yield: 75%) confirmed19F-NMR with triptorelin as an internal standard. 5-Trifluoromethyl-3',5'-di-O-acetyl-2'-deoxyuridine get in a solid white color (0,19 g, yield: 50%) by chromatography on a column.

1H-NMR (deuterated chloroform): δ 2,10 (s, 3H), 2.13 and (s, 3H), 2,19 (DDD, J=6,63 Hz, 8,00 Hz, 14,34 Hz, 1H), 2.63 in (DDD, J=1,96 Hz, 5,72 Hz, 14,34 Hz, 1H), 4,28-4,37 (m, 2H), of 4.44 (DD, J=2.66 Hz, 11,77 Hz, 1H), 5,23 (TD, J=1,96 Hz, 6,63 Hz, 1H), 6,28 (DD, J=5,72 Hz, 8,00 Hz, 1H), of 8.09 (s, 1H), 9,27 (s, 1H).

13C-NMR (deuterated chloroform): δ 20,5, 20,9, 38,7, 63,7, 74,0, 83,1, 86,1, 105,7 (square, with JCF=33.3 Hz), 121,7 (sq, s, JCF=270,2 Hz), 140,0 (sq, s, JCF=5,91 Hz), 149,2, 158,1, 170,2, 170,4.

19F-NMR (deuterated chloroform): δ -63,7.

EXAMPLE 25

0.11 g (1.0 mmol) of Cytosine is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Arr is irreducible 5-triptoreline ( 19F-NMR yield: 27%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Cryptometrics get in a solid white color (0,010 g, yield: 5.6 per cent) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 6,95 (users, 2H), 7,72 (users, 2H), 7,95 (s, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 94,3 (sq, s, JCF=33,5 Hz), 124,2 (sq, s, JCF=268,7 Hz), 145,8, 156,0, 161,5.

19F-NMR (deuterated dimethyl sulfoxide): δ -60,8.

MS (m/z): 181[M]+.

EXAMPLE 26

0.15 g (1.0 mmol) of N4-Acetylcytosine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 17 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of N4-acetyl-5-triptoreline (19F-NMR yield: 35%) confirmed19F-NMR with 2,2,2-triptoreline as an internal art is ngarta. N4-acetyl-5-cryptometrics get in a solid white color (0,067 g, yield: 30%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ of 2.56 (s, 3H), of 8.04 (s, 1H), 11,58 (users, 2H).

13C-NMR (deuterated dimethyl sulfoxide): δ 23,0, to 102.3(sq, s, JCF=31,9 Hz), 123,4 (sq, s, JCF=268,8 Hz), 144,7 (sq, s, JCF=5,6 Hz), 151,2, 160,5, 172,1.

19F-NMR (deuterated dimethyl sulfoxide): δ-61,8.
MS (m/z): 224[M+H]+.

EXAMPLE 27

0.24 g (1.0 mmol) of Cytidine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 4,0 ml of dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-triftormetilfullerenov (19F-NMR yield: 24%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Triptorelin get (0,034 g, yield: 11%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 3,2 (m, 1H), 3,70 (m, 1H), 3.96 points (m, 3H), 5,00 (d, J=13,6 Hz, 1H), 5,28 (t, J=5.4 Hz, 1H), 5,48 (d, J=13,6 Hz, 1H), USD 5.76 (m, 1H), 7,16 (users, 1H), 7,72 (users, 2H), 8,84 (s, 1H).

19F-NMR (deuterated dimethyl sulfoxide): δ -60,9.

EXAMPLE 28

0.15 g (1.0 mmol) of 2'-Deoxycytidine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 5-trifluoromethyl-2'-deoxycytidine (19F-NMR yield: 11%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 5-Trifluoromethyl-2'-deoxycytidine get in a solid white color (0.01 g, output: 3,3%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ of 2.16 (m, 2H), 3,62 (m, 2H), 3,82 (m, 1H), 4,20 (m, 1H), is 5.06 (d, J=12,5 Hz, 1H), 5,19 (d, J=12,5 Hz, 1H), 6,04 (t, J=5.6 Hz, 1H),? 7.04 baby mortality (users, 1H), to 7.64 (users, 2H), at 8.60 (s, 1H).

19F-NMR (deuterated of dimethylsulfate is): δ-60,8.

EXAMPLE 29

of 0.13 g (1.0 mmol) of Adenine are weighed and placed in a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptoreline (19F-NMR yield: 26%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Triptorelin get in a solid white color (0.02 g, yield: 10%) using preparative thin-layer chromatography.

1H-NMR (deuterated dimethyl sulfoxide): δ 8,31 (s, 1H), 14,08 (users, 2H).

13C-NMR (deuterated dimethyl sulfoxide): δ 119,9, to 121.0 (square, JCF=270,2 Hz), 147,1, 147,1, 150,9, 156,8.

19F-NMR (deuterated dimethyl sulfoxide): δ-62,9.

MS (m/z): 203[M]+

EXAMPLE 30

0.27 g (1.0 mmol) of Adenosine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with m gnanam rotor, and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 4,0 ml of dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triftormetilfosfinov (19F-NMR yield: 6.7 per cent) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Tripteroides get in a solid white color (0.01 g, yield: 3.1 per cent) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 3,62 (m, 2H), Android 4.04 (m, 1H), 4,23 (m, 1H), of 5.05 (DD, 1H), 5,24 (m, 1H), 5,52 (m, 2H), of 5.81 (d, 1H), 7,92 (users, 2H), 8,24 (s, 1H).

19F-NMR (deuterated dimethyl sulfoxide): δ-60,2.

EXAMPLE 31

0.15 g (1.0 mmol) of 2,6-Diaminopurine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 4,0 ml of dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous solution of the peroxide is hydrogen. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 2,6-diamino-8-triptorelin (19F-NMR yield: 45%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 2,6-Diamino-8-triptorelin get in a solid white color (0,050 g, yield: 23%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ of 6.17 (s, 2H), 7,26 (s, 2H), 12,2 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 114,8, 116,0 (square, JCF=269,1 Hz), 144,3, 152,7, 157,0, 161,7.

19F-NMR (deuterated dimethyl sulfoxide): δ-62,6.

MS (m/z): 218[M]+.

EXAMPLE 32

0.15 g (1.0 mmol) of 2,6-Diaminopurine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 3.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1,3 ml traducator-1-hodgekin, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. The formation of 2,6-diamino-8-PE is perhexiline ( 19F-NMR yield: 10%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 2,6-Diamino-8-PerformancePoint get in a solid white color (0,018 g, output: 4,0%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ of 6.20 (s, 2H), 7,31 (s, 2H), 12,2 (users, 1H).

19F-NMR (deuterated dimethyl sulfoxide): δ -126,2 (sq, JFF=4,7 Hz, 2F), -122,9 (users, 2F), -121,9 (m, 4F), -108,9 (m, 2F), -80,7 (t, JFF=9.5 Hz, 3F)

MS (m/z): 469[M+H]+.

EXAMPLE 33

0.15 g (1.0 mmol) of Guanine weighed and placed in a 500 ml 2-necked flask equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 197 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-cryptomelane (19F-NMR yield: 46%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Cryptomelane get in a solid white color 0,019 g, yield: 9%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 6,60 (users, 2H), 10,81 (users, 1H), 13,73 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 116,3, 119,2 (square, JCF=269,3 Hz), 134,9 (square, JCF=40,7 Hz), 152,8, 154,7, 156,6.

19F-NMR (deuterated dimethyl sulfoxide): δ-63,0.

MS (m/z): 218[M-H]-.

EXAMPLE 34

0,41 g (1.0 mmol) 2',3',5'-Three-O-acetylcarnosine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-trifluoromethyl-2',3',5'-three-O-acetylcarnosine (19F-NMR yield: 51%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Trifluoromethyl-2',3',5'-three-O-acetylcarnosine is obtained as a solid yellow (0,22 g, yield: 47%) using chromatography on a column of silica gel.

1H-NMR (deuterated chloroform): δ 2,03 (s, 3H), 2.13 and (s, 3H), of 2.16 (s, 3H), 4,30 (m, 1H), of 4.44 (m, 2H), by 5.87 (t, J=5.0 Hz, 1H), 5,94 (d, J=5.0 Hz, 1H), 6,47 (users, 2H), 12,1 (s, 1H).

13C-NMR (deuterated chloroform): δ 20,3, 20,5, 20,6, 62,9, 70,6, 71,6, 77,2, 80,6, 87,6, 116,4, 118,3 (square, JCF=270,5 Hz), 152,6, 154,6, 158,9, 169,5, 169,5, 170,8.

19F-NMR (deuterated chloroform): δ -61,5.

EXAMPLE 35

0.39 g (1.0 mmol) 2',3',5'-Three-O-acetyltyrosine weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 5,0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-trifluoromethyl-2',3',5'-three-O-acetyltyrosine (19F-NMR yield: 7.0 percent) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Trifluoromethyl-2',3',5'-three-O-acetaminopen get (0,018 g, output: 4,0%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ of 2.08 (s, 6H), of 2.16 (s, 3H), 4,35 is 4.45 (m, 2H), 4,51 (DD, J3,6, 11.3 Hz, 1H), 5,73 (DD, J=a 5.5, and 5.6 Hz, 1H), between 6.08 (d, J=5.5 Hz, 1H), 6,27 (DD, J=5.6 Hz, 1H), compared to 8.26 (s, 1H), 12,49 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 20,2, 20,5, 20,7, 62,8, 70,3, 72,0, 80,7, 88,0, 118,1 (square, JCF=271,7 Hz), 124,2, 138,2 (square, JCF=40,7 Hz), 147,2, 150,1, 158,6, 169,2, 169,5, 170,5.

19F-NMR (deuterated dimethyl sulfoxide): δ-61,5.

EXAMPLE 36

0.14 g (1.0 mmol) Gipoksantina and 0,058 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 60 to 70°C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triftormetilfosfinov (19F-NMR yield: 24%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Triftormetilfosfinov get (0,026 g, yield: 13%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 8,13 (s, 1H), to 12.52 (s, 1H), 14,89 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 119,0 (square, JCF=270,1 Hz), 22,6, 138,0 (square, JCF=41,2 Hz), 147,6, 152,3, 156,4.

19F-NMR (deuterated dimethyl sulfoxide): δ -63,2.

MS (m/z): 205[M+H]+.

EXAMPLE 37

to 0.19 g (1.0 mmol) Xanthine weighed and placed into a 2-necked flask of 100 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 47 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triftormetilfosfinov (19F-NMR yield: 44%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Triptoreline get (0,044 g, yield: 20%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 11,16 (s, 1H), 11,83 (s, 1H), 15,07 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 110,0, 118,7 (square, JCF=269,9 Hz), 138,0 (square, JCF=41,1 Hz), 148,1, 151,7, 156,2.

19F-NMR (deuterated dimethyl sulfoxide): δ -63,1.

MS (m/z): 221[M+H]+.

EXAMPLE 38

to 0.19 g (1.0 mmol) of Caffeine is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 17%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Triptorelin get in a solid white color (0,033 g, yield: 13%) using chromatography on a column.

1H-NMR (deuterated acetone): δ of 3.33 (s, 3H), 3,52 (s, 3H), 4,21 (sq, JHF=1,25 Hz, 3H).

13C-NMR (deuterated acetone): δ 27,8, 29,7, 33,3 (square, JCF=1,98 Hz), 110,3, 119,2 (square, JCF=270,2 Hz), 138,4 (square, JCF=39,6 Hz), 147,0.

19F-NMR (deuterated acetone): δ -62,1 (l, JHF=1,25 Hz)

MS (m/z): 262[M]+.

EXAMPLE 39

Education 8-triptorelin (19F-NMR yield: 48%) confirm in accordance with a technique similar to the method presented in the Application is e 38, except that 0.5 ml of 1N. solution of sulfuric acid in dimethyl sulfoxide is used instead of 2.0 ml of 1N. sulfuric acid solution in dimethyl sulfoxide.

EXAMPLE 40

of 1.94 g (10 mmol) of Caffeine is weighed and placed into a 2-necked flask of 100 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following ingredients: 20 ml of dimethyl sulfoxide, 20 ml of 1N. solution of sulfuric acid in dimethyl sulfoxide, 10 ml of a 3.0 mol/l solution of triptoreline in dimethylsulfoxide, 3.0 ml of 1.0 mol/l aqueous solution of ferric sulfate and 2.0 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 50 to 60°C for 60 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 20%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 41

of 1.94 g (10 mmol) of Caffeine is weighed and placed into a 2-necked flask of 300 ml equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following ingredients: 50 ml of dimethyl sulfoxide, to 0.055 ml of concentrated sulfuric acid, 30 mmol gaseous triptoreline, 3.0 ml of 1.0 mol/l aqueous solution of ferric sulfate and 2.0 ml of 30% aqueous hydrogen peroxide solution, the Mixture is stirred in the temperature range from 50 to 60°C for 60 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 23%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 42

Education 8-triptorelin (19F-NMR yield: 15%) is confirmed in accordance with methods similar to the methods described in Example 41, except that 1.0 mol/l aqueous solution of ammonium ferric sulfate is used instead of 1.0 mol/l aqueous solution of ferric sulfate.

EXAMPLE 43

to 0.19 g (1.0 mmol) of Caffeine is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: of 0.21 ml of a 42% aqueous solution terraforming acid, 4.0 ml of dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of tetrafluoroborate iron and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 11%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 44

to 0.19 g (1.0 mmol) of Caffeine is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magni is the principal rotor, and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 0,016 g (0.3 mmol) of iron powder, 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 37%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard.

EXAMPLE 45

to 0.19 g (1.0 mmol) of Caffeine and 0,056 g (0.3 mmol) of ferrocene is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of an aqueous solution of hydrogen peroxide. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 17%) confirmed19F-NMR with 2,2,2-trifluoroethane is scrap as an internal standard.

EXAMPLE 46

Education 8-triptorelin (19F-NMR yield: 13%) confirm in accordance with a technique similar to the method presented in Example 41 except that the reaction is carried out in an atmosphere of air without replacement with argon.

EXAMPLE 47

0.18 g (1.0 mmol) of Caffeine is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 3.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1,3 ml traducator-1-hodgekin, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-perftorgeksilsilanami (19F-NMR yield: 30%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Perftorgeksil get in a solid white color (0,077 g, yield: 15%) using chromatography on a column.

1H-NMR (deuterated acetone): δ of 3.33 (s, 3H), 3,52 (s, 3H), 4,21 (s, 3H).

19F-NMR (deuterated acetone): δ -125,9 (m, 2F), -122,8 (s, 2F), -122,0 (m, 2F), -114,2 (m, 4F), -80,5 (sq, JFF=9.4 Hz, 3F).

MS (m/z): 513[M+H]+.

EXAMPLE 48

0.18 g (1.0 mmol) of Theobromide weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 17 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triftormetilfullerenov (19F-NMR yield: 12%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Cryptomaterial get in a solid white color (0,024 g, yield: 10%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ to 3.34 (s, 3H), Android 4.04 (s, J=1.7 Hz, 3H), 11,48 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 33,1 (square, JCF=1.9 Hz), 42,1, 109,9 (square, JCF=1.9 Hz), 118,2 (square, JCF=270,7 Hz), 137,0 (square, JCF=39,2 Hz), 147,5, 150,6, 155,2.

19F-NMR (deuterated dimethyl sulfoxide): δ -61,6.

MS (m/z): 248[M]+.

EXAMPLE 49

0.18 g (1.0 mmol) Theo is Illina weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following products: 2.0 ml of dimethyl sulfoxide, 2.0 ml, 1N. solution of sulfuric acid in dimethyl sulfoxide, 1.0 ml of 3.0 mol/l solution of triptoreline in dimethyl sulfoxide, 0.2 ml of 30% aqueous hydrogen peroxide solution and 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-triptorelin (19F-NMR yield: 48%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Trifloromethyl get in a solid white color (0,086 g, yield: 35%) using chromatography on a column.

1H-NMR (deuterated dimethyl sulfoxide): δ 3.24 in (s, 3H), 3,42 (s, 3H), 15,2 (users, 1H).

13C-NMR (deuterated dimethyl sulfoxide): δ 27,9, 29,9, 109,1, 118,2 (square, JCF=270,0 Hz), 137,3 (square, JCF=37,2 Hz), 146,8, 150,9, 154,6.

19F-NMR (deuterated dimethyl sulfoxide): δ -62,3.

MS (m/z): 248[M]+.

EXAMPLE 50

0.18 g (1.0 mmol) of theophylline is weighed and placed into a 2-necked flask with a volume of 50 ml, equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. Then in the specified flask add the following shall roducti: 3.0 ml of dimethyl sulfoxide, 2.0 ml 1N. solution of sulfuric acid in dimethyl sulfoxide, 1,3 ml traducator-1-hodgekin, 0.3 ml of 1.0 mol/l aqueous solution of ferric sulfate and 0.2 ml of 30% aqueous hydrogen peroxide solution. The mixture is stirred in the temperature range from 40°to 50 ° C for 20 minutes and then the resulting solution is cooled to room temperature. Education 8-perftorgeksilsilanami (19F-NMR yield: 12%) confirmed19F-NMR with 2,2,2-triptoreline as an internal standard. 8-Performancelevel get in a solid white color (0.02 g, yield: 4.0 per cent) using chromatography on a column.

1H-NMR (deuterated acetone): δ to 3.34 (s, 3H), of 3.57 (s, 3H), 14,2 (users, 1H).

19F-NMR (deuterated acetone): δ -127,0 (m, 2F), -123,6 (users, 2F), -122,9 (m, 2F), -122,4 (users, 2F), -112,3 (m, 2F), -81,9 (t, JFF=7,1 Hz, 3F).

MS (m/z): 499[M+H]+.

EXAMPLE 51

The formation of 6-(2-chloroethyl)-5-cryptomaterial (19F-NMR yield: 55%) confirm in accordance with methods similar to the methods described in Example 22, except that 0.16 g of 6-(2-chloroethyl)uracil is used instead of 0.37 g of 2',3',5'-tri-O-acetylornithine. Then 6-(2-chloroethyl)-5-cryptomaterial get in a solid white color (0.10 g, yield: 45%) using preparative thin-layer chromatography.

Industrial application

<> Nucleic acid base having performanceline group in accordance with the present invention, is useful as a drug, intermediate compounds for medical and agricultural chemicals, and so forth.

Full disclosure of the patent application of Japan No. 2005-324943 registered 9 November 2005, including the description, the claims and the invention included in this application by reference in its entirety.

1. A method of obtaining a nucleic base, having performanceline group, including: carrying out a reaction of nucleic bases with performancingads represented by the General formula (2):

where Rf represents a C1-C6performanceline group and X represents a halogen atom, in the presence of a sulfoxide represented by the General formula (I)

where each of R1aand R1brepresents a C1-C12alkyl group or optionally substituted phenyl group, peroxide and compounds of iron.

2. The method according to claim 1, characterized in that the reaction is carried out in the presence of acid.

3. The method according to claim 1 or 2, characterized in that the nucleic acid base is orally represented by the General formula (3)

DG is R 2represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R3represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and R4represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted C1-C4alkoxygroup, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; cytosine represented by the General formula (4)

where R5represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R6represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; and each of R7and R8represents a hydrogen atom or a protective group for nitrogen; Aden the us, represented by the General formula (5)

where R9represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, R represents a hydrogen atom, optionally substituted C1-C6alkyl group, optionally substituted by an amino group, carboxyl group, optionally substituted karbamoilnuyu group or optionally substituted C2-C5alkoxycarbonyl group; and each of R11and R12represents a hydrogen atom or a protective group for nitrogen; guanine represented by the General formula (6)

where R13represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R14represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and each of R15and R16represents a hydrogen atom or a protective group for nitrogen; hypoxanthine represented by the General formula (7)

where R17represents a hydrogen atom, optionally substituted C1-C6alkyl group and the protective group for the nitrogen, and R18represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues; or xantina represented by the General formula (8)

where R19represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for a nitrogen, R20represents a hydrogen atom, optionally substituted C1-C6alkyl group, a protective group for nitrogen, or one of pentony residues and their analogues, and R21represents a hydrogen atom, optionally substituted C1-C6alkyl group or a protective group for the nitrogen.

4. The method according to claim 3, characterized in that the nucleic acid base is orally represented by the General formula (3)

where R2, R3and R4are the same as defined above.

5. The method according to claim 1, characterized in that X represents iodine or bromine.

6. The method according to claim 1, wherein Rf represents triptorelin group or perforation group.

7. The method according to claim 1, characterized in that the compound of iron is a ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, ferric chloride, bromide is elesa, iodide of iron, iron acetate, iron oxalate, bis(acetylacetonate)iron(II), ferrocene, bis (η5-pentamethylcyclopentadienyl)iron or iron powder.

8. The method according to claim 7, characterized in that the compound of iron is a ferrous sulfate, ammonium ferrous sulfate, tetrafluoroborate iron, ferrocene or iron powder.

9. The method according to claim 1, characterized in that the peroxide is hydrogen peroxide, the composite hydrogen peroxide-urea, tert-butyl peroxide or peroxidase acid.

10. The method according to claim 9, characterized in that the peroxide is hydrogen peroxide or a composite hydrogen peroxide-urea.

11. The method according to claim 2, characterized in that the acid is a sulfuric acid, hydrochloric acid, hydrogen bromide, hydrogen iodide, nitric acid, phosphoric acid, hexaphosphoric acid, tetracarbonyl acid, formic acid, acetic acid, propionic acid, oxalic acid, p-toluensulfonate acid, triftormetilfullerenov acid or triperoxonane acid.

12. The method according to claim 11, characterized in that the acid is a sulfuric acid, tetracarbonyl acid or triftormetilfullerenov acid.

13. The method according to claim 1, wherein each of R1aand R1brepresents a methyl group, boutelou groups is or phenyl group.

14. The method according to claim 1, characterized in that the temperature of the reaction mixture is in the range from 20 to 100°C.

15. The method according to claim 1, characterized in that the pressure of the reaction is in the range from atmospheric pressure to 0.1 MPa to 1.0 MPa.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to phosphoramidite derivatives of general formula where Bx denotes adenine, guanine, cytosine, thymine or uracil, where the amine group of adenine, guanine and cytosine can be optionally protected by a protective group selected from acetyl and phenoxyacetyl; R1 is a substitute of general formula in which R11, R12 and R13 are identical or different, and each denotes hydrogen or alkoxy; R2a and R2b are identical or different, and each denotes alkyl; and WG1, WG2 denote a cyano group. The invention also pertains to a multistep method of producing the said compounds. The invention also relates to intermediate compounds of the said method, namely: an intermediate ether compound of general formula where L is a halogen or a C1-C5alkylthio group; WG1 is a cyano group; an intermediate compound of general formula where Bx denotes adenine, guanine, cytosine, thymine or uracil, where the amine group of adesine, guanine and cytosine can be optionally protected by a protective group selected from an acetyl group and a phenoxyacetyl group; and WG1 denotes a cyano group; an intermediate compound of general formula where Bx is as described above; R1 is a substitute of general formula (2); an intermediate compound of general formula where Bx is as described above; A is a silicon-containing substitute of general formula or where R6 denotes alkyl and WG1 denotes a cyano group. The invention also relates to a method of producing an oligonucleotide of general formula where each B independently denotes adenine, guanine, cytosine, uracil or thymine; each R independently denotes H or hydroxyl and at least one of R denotes hydroxyl; Z denotes H or a phosphate group; and n is an integer between 1 and 100, involving steps A-G, characterised by use of said phosphoramidite derivatives as a monomer compound of nucleic acid at step B.

EFFECT: high yield.

7 cl, 1 dwg, 21 ex

FIELD: chemistry.

SUBSTANCE: in compound of formula (I): , R1 represents C1-4-alkoxy C3-6cycloalkyl optionally substituted with atom of halogen, hydroxyl, trifluoromethyl, optionally substituted with halogen atom 5-6-member heterocyclyl, in which heteroatoms are selected from oxygen, optionally substituted with halogen atoms phenyl or optionally substituted with halogen atoms 5-6-member heteroaryl, in which heteroatoms are selected from nitrogen and/or sulfur; R2 represents hydrogen or trifluoromethyl; R3 represents hydrogen, optionally substituted with atom of halogen, C3-6cycloalkyl, optionally substituted with atom of halogen, trifluoromethyl, C1-4-alkyl phenyl, optionally substituted with atom of halogen, trifluoromethyl, C1-4-alkoxy heterocyclyl, which has in ring 1-2 heteroatoms, selected from nitrogen, oxygen or sulfur, or optionally substituted with C1-4-alkyl 5-6-member heterocyclyl, which has in ring 1-2 heteroatoms, selected from nitrogen or oxygen, R4 and R5 independently represent hydrogen; X represents covalent bond or lower alkylene; X1 represents covalent bond or lower alkylene, Y represents covalent bond or lower alkylene, optionally substituted with hydroxy or cycloalkyl; and Z represents -C=C-, -R6C=CR7- or -CHR6CHR7-, where R6 and R7 in each position represent hydrogen or lower alkyl.

EFFECT: antilipolytic effect of compounds.

30 cl, 7 dwg, 31 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to the method of obtaining 2-amino-6-azido-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine and can be used in organic chemistry and pharmaceutical industry. The method lies in that, 2-amino-6-azido-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine and sodium azide interact in the presence of the above mentioned tetrametylammonium chloride boiled for 4 hours in absolute acetonitrile. The obtained compound is cleaned by elution of benzol. The residue is dissolved in chloroform and the desired product is separated during precipitation using hexane.

EFFECT: high degree of purity with high output.

1 ex

FIELD: chemistry.

SUBSTANCE: method implies that suspension 2-amino-6-azido-9-(2,3,5-tri-O-acetyl-β-D-ribofuranozile)purine in 60% anhydrous hydrogen fluoride solution of pyridine is diazotizied with tert-butylnitrite during 1 hour at (-18) - (-22)°C. Reaction mixture is decomposed with cut ice. Reaction product is purified by, flash-chromatography on aluminum oxide. Then produced 2-fluorine-6-azido-9-(2,3,5-tri-O-acetyl-β-D-ribofuranozile)purine is hydrogenated at air pressure in 10% acetic acid solution of absolute ethyl acetate with 10% palladium on carbon solution occurrence during 18 hours. Reaction product is purified in acetonitrile solution by flash-chromatography on aluminum oxide at 50-55°C and crystallized from alcohol.

EFFECT: production of compound of high purity with high output.

2 ex

FIELD: chemistry.

SUBSTANCE: invention applied for relates to process of obtaining 2,6- dichlor-9-(2,3,5-tru-O-acetyl-β-D-ribofuranozyl) purine and may be used in organic chemistry and pharmaceutical industry. The process involves conduction of 2,6- dichlor-9-(2,3,5-tru-O-acetyl-β-D-ribofuranozyl) purine with tret-butyl nitrite in the methylene chloride medium at (-18)-(-22)°C during 2 hours in presence of pyridine hydrochloride and phosphorus oxychloride followed by decomposing the reaction mixture with chipped ice, and cleansing of the target product in methylene chloride with flash-chromatography on silica gel.

EFFECT: obtaining of substance with high grade of purity and high output by simplified technology.

1 ex

FIELD: chemistry.

SUBSTANCE: this invention covers method of production of 2-chloroadenosine and may be used in organic chemistry and pharmaceutical industry. The method includes ammonolysis of 2.6-di-chloro-9-(2,3,5-tri-O-acetyl-(β-O-ribofuranozyl)purine in absolute ethyl acetate saturated with ammonia at 0°C during 3 days with further hydrolysis of obtained 5'-0-acetyl-2-chloro-adenosine with 20% ammonia solution in methanol at 20°C during 6 hours, isolation of desired product from the reaction mixture by boiling in mixture of chloroform and methanol, their volumetric ratio 3:1, and purification by crystallization from water.

EFFECT: production of substance with high purity.

1 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I) wherein each among R represents independently hydrogen atom, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, phenyl or phenyl-(C1-C3)-alkyl; X and X' represent -CH2OH, -CO2R2, -OC(O)R2, -CH2OC(O)R2 or C(O)NR3R4 wherein R2, R3 and R4 represent independently hydrogen atom (H), (C1-C6)-alkyl substituted optionally with one-three (C1-C6)-alkoxy-groups, (C1-C6)-alkylthio-groups, halogen atoms, hydroxy-, amino-, mono-(C1-C6)-alkyl)-amino-, di-(C1-C6)-alkyl)-amino-group; Z and Z' represent independently (C1-C6)-alkyl broken optionally with one-three sulfur atoms (S) or non-peroxide oxygen atom (O), or they absent; n = 1-3; or to its pharmaceutically acceptable salt. Compounds are agonists of adenosine A2A-receptors and can be used for inhibition of inflammatory response or inflammation treatment.

EFFECT: valuable medicinal properties of compounds.

56 cl, 1 tbl, 21 dwg, 37 ex

The invention relates to nucleoside analogs of formula (1) in which R1represents H or a group protecting the hydroxyl, R2represents H, a group protecting the hydroxyl group of phosphoric acid, a protected group, phosphoric acid or a group of the formula P(R3R4in which R3and R4are the same or different and represent a hydroxyl group, a protected hydroxyl group, alkoxygroup, allylthiourea, cyanoacetylurea, amino group, substituted alkyl group; And represents alkylenes group containing from 1 to 4 carbon atoms, and a represents a substituted purine-9-ilen group or substituted 2-oxopyrimidine-1-ilen group containing at least one Deputy, selected from hydroxyl groups, protected hydroxyl groups, amino groups, protected amino groups, alkyl groups

The invention relates to medicine and provides substances that are effective against tumors and viruses, for which conventional anti-tumor agents and antiviral agents exhibit only insufficient effects, and have cancerostatic action and antiviral effects on different tumor immune

The invention relates to certain oxipurinol the nucleosides, compounds related data oxipurinol the nucleosides, acyl derivatives and compositions that contain at least one of these compounds

FIELD: chemistry.

SUBSTANCE: invention relates to 5'-urethane AZT derivatives of general formula

where X = -NH2, -NHMe, -NHEt, .

EFFECT: compounds have low toxicity, can efficiently inhibit reproduction of the immunodeficiency virus type 1 virus in a CEM SS cell culture.

1 cl, 2 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) where R1 is chosen from ethyl, n-propyl, isopropyl or isobutyl, and to its pharmaceutically acceptable salts. Besides, the invention refers to a pharmaceutical composition on the basis of said compounds used for treating a hepatitis C virus (HCV) mediated disease, and also to a method of treating the hepatitis C virus (HCV) mediated disease, and to the method of selective O-acylation nucleoside II for producing O-acyl nucleoside I in an alkaline reaction medium including the stages: (i) dissolution of II and DMAP in a heterogeneous mixture of water and a solvent and addition of a water base for pH control between approximately 7.5 to approximately 12; (ii) optional addition of a sufficient amount of saturated aqueous NaCl for preparing a diphase reaction mixture; (iii) addition of an acidating agent and an accessory base sufficient for pH preservation between approximately 7.5 to approximately 12; (iv) reaction monitoring and interruption of adding said acidating agent and said base after sufficient conversion provided; (v) optional contact of O-acylnucleoside with the pharmaceutically acceptable acid to produce a pharmaceutically acceptable salt.

EFFECT: production of the pharmaceutical composition for treating the hepatitis C virus (HCV) mediated disease.

9 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a pyrimidine nucleoside compound of general formula (1) , in which one of X and Y is a cyano group and the other is hydrogen; R1 is hydrogen, (R3)(R4)(R5)Si- or a carbonyl group which includes an alkyl monosubstituted with an amino group; R2 is hydrogen or (R6)(R7)(R8)Si-, provided that at least one of R1 and R2 is not hydrogen; or R1 and R2 together form a 6-member cyclic group -Si(R9)(R10)-, where each of R9 and R10 is a straight or branched alkyl; R3, R4 and R5 denote a straight or branched alkyl optionally substituted alkoxy, or cycloalkyl; R6, R7 and R8 denote a straight or branched alkyl optionally substituted alkoxy, cycloalkyl or phenyl, or to pharmacologically acceptable salts thereof. The invention also relates to a range of specific compounds of formula (1) or to their pharmacologically acceptable salts: 5'-O-triisopropylsilyl-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 5'-O-diethylisopropylsilyl-2'-cyano-2,-desoxy-1-β-D-arabinofuranosylcytosine; 5'-O-dimethylthexylsilyl-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 5'-O-(dimethyl-n-octylsilyl)-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 3'-O-dimethylthexylsilyl-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 3'-O-diethylisopropylsilyl -2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 3'-O-(tert-butyldimethylsily)-2'-cyano-2'-desoxy-1-β-O-arabinofuranosylcytosine; 3'-O-triisopropylsilyl-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 3'-O-dimethylthexylsilyl-5'-O-(L-valyl)-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; 5'-O-(L-valyl)-3'-O-(tert-butyldimethylsilyl)-2'-cyano-2'-desoxy-1-β-D-arabinofuranosylcytosine; and 3'-O-cyclopropyl-diisopropylsilyl-2'-cyano-2'-desoxy-1-β-D- arabinofuranosylcytosine.

EFFECT: obtaining formula (1) compounds or their pharmacologically acceptable salts for preparing a medicinal agent for treating tumours.

9 cl, 20 tbl, 1 dwg, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the method of producing 2'-desoxy-β-L-thymidine, which involves reacting 5'-O-trityl- or 5'-O-dimethoxytrityl- substituted 2,2' -anhydro-1 -β-L- arabinofuranosylthymine with a reducing agent RedAl and a complexing agent 15-crown-5-ether in a polar solvent 1,2-dimethoxyethane (DME) or tetrahydrofuran, obtaining 5'-O-trityl- or 5'-O-dimethoxytrityl- substituted 2,2'-desoxy-β-L-thymidine, subjected to protection removal if necessary. The invention also relates to the method of producing 2'-desoxy-β-L-thymidine, which involves reacting L-arabinose with cyanamide with subsequent reaction of the intermediate product - L-arabinofuranosylaminooxazoline - with a cycling or condensing agent, forming 2,2' -anhydro-1-β-L-arabinofuranosylthymine; reaction of the latter with a reducing agent RedAl and a complexing agent 15-crown-5-ether in a polar solvent 1,2-dimethoxyethane (DME) or tetrahydrofuran, obtaining 2'-desoxy-β-L-thymidine, where L-arabinofuranosylaminooxazoline can be protected by trityl or dimethoxytrityl in position 5' before or after reaction with the cycling or condensing agent; and protection removal of optionally protected 2'-desoxy-β-L-thymidine, if this is necessary or desired. Use in the given methods of such a reducing agent as Red-Al, and such a complexing agent as 15-crown -5-ether, causes a reaction of intramolecular protection and production of the required nucleoside product with good output.

EFFECT: compound is of great importance as an antiviral or antineoplastic preparation.

13 cl, 29 dwg, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining enriched with β-anomer 2'-desoxy-2',2'-difluorocytidine of formula (I)

, which includes stages: (i) interaction of enriched with α-anomer compound of 1-halogenribofuranose of formula (III) with nucleic base of formula (IV) in solvent obtaining enriched with β-anomer nucleoside of formula (II) , with constant removal of formed in reaction process silylhalogenide of formula R3SiX (V) by distillation using carrier or running inert gas through reaction mixture; and (ii) removal of protective group from enriched with β-anomer nucleoside of formula (II). Invention also relates to method of obtaining hydrate of enriched with β-anomer 2'-desoxy-2',2'-difluorocytidine of formula (I), which at stage (ii) after removal of protective group additionally includes stages of dissolving formula (I) nucleoside in water; heating of obtained solution to temperature from 40 to 60°C; cooling of solution to temperature ranging from 10 to 25°C with or without mixing and without changing pH; and filtering of deposited solid substances.

EFFECT: method improvement.

17 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to (2'R)-2'-dezoxy-2'-fluoro-2'-C-methylnucleoside (β-D or (β-L) , where X represents O; R1 and R7 independently represent H; R3 represents hydrogen and R4 represents NH2; or its pharmaceutically acceptable salt. The invention also pertains to the method of producing the said compounds, which involves glycosylation of N4-benzoylcytosine with a compound of formula 1-4, where R represents methyl, Pg is chosen from C(O)Ph, CH2Ph or both Pg groups can be included in 1,3-(1,1,3,3-tetraisopropyldisiloxanylidene); with further removal of protection of 3'-OPg and 5'-OPg and N-benzoyl of the obtained product.

EFFECT: invented compounds or their pharmaceutically acceptable salts are used as active ingredients against Flaviviridae family viruses in pharmaceutical compositions and liposomal pharmaceutical compositions.

4 cl, 9 tbl, 5 ex, 4 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to method of gemcitabine hydrochloride purification, which includes enriching gemcitabine hydrochloride with its p-anomer, according to which solution of gemcitabine hydrochloride in water is taken with ratio of water to gemcitabine hydrochloride from 3:1 to 12:1 (wt/vol); solution is processed with activated coal, activated coal being taken in amount from 0.1 to 10 wt % of gemcitabine hydrochloride amount in solution; activated coal is removed from solution with formation of filtered solution; concentration of gemcitabine hydrochloride in filtered solution is increased until ratio of filtered solution to gemcitabine hydrochloride equals from 1:1 to 1:5 (wt/vol), efficient for gemcitabine hydrochloride sedimentation; deposited gemcitabine hydrochloride is isolated; and in case admixture content in deposited gemcitabine hydrochloride is not reduced to required level, stages (a)-(e) are repeated. Claimed invention also relates to method of obtaining gemcitabine hydrochloride using claimed purification method.

EFFECT: creation of efficient method of gemcitabine hydrochloride purification.

5 cl, 1 tbl, 5 dwg, 8 ex

FIELD: medicine, pharmacology, bioorganic chemistry, pharmacy.

SUBSTANCE: invention relates to the effective using amount of β-L-2'-deoxynucleoside of the formula (I) or (II) used in manufacturing a medicinal agent used in treatment of hepatitis B, pharmaceutical compositions containing thereof, and methods for treatment of hepatitis B. Proposed agent shows the enhanced effectiveness in treatment of hepatitis B.

EFFECT: enhanced and valuable medicinal properties of agent.

83 cl, 6 tbl, 11 ex

FIELD: organic chemistry, biochemistry, medicine, virology.

SUBSTANCE: invention relates to derivatives of 2'=amino-2'-deoxynucleosides of the formula:

wherein R means hydrogen atom (H), alkyl, aminoalkyl; R1 means -(R2NR3) wherein R2 and/or R3 means H, -OH, -NH2, alkyl, benzyl under condition that R doesn't represent H or methyl when R2 and R3 mean H. Compounds elicit an antiviral activity with respect to measles and Marburg viruses exceeding that of ribavirin.

EFFECT: valuable properties of compounds.

4 tbl, 2 dwg, 18 ex

The invention relates to a derivative of gemcitabine formula (I), where R1, R2, R3independently selected from hydrogen and C18and C20saturated and monounsaturated acyl groups, provided that R1, R2, R3can't all be hydrogen

FIELD: chemistry.

SUBSTANCE: invention relates to phosphoramidite derivatives of general formula where Bx denotes adenine, guanine, cytosine, thymine or uracil, where the amine group of adenine, guanine and cytosine can be optionally protected by a protective group selected from acetyl and phenoxyacetyl; R1 is a substitute of general formula in which R11, R12 and R13 are identical or different, and each denotes hydrogen or alkoxy; R2a and R2b are identical or different, and each denotes alkyl; and WG1, WG2 denote a cyano group. The invention also pertains to a multistep method of producing the said compounds. The invention also relates to intermediate compounds of the said method, namely: an intermediate ether compound of general formula where L is a halogen or a C1-C5alkylthio group; WG1 is a cyano group; an intermediate compound of general formula where Bx denotes adenine, guanine, cytosine, thymine or uracil, where the amine group of adesine, guanine and cytosine can be optionally protected by a protective group selected from an acetyl group and a phenoxyacetyl group; and WG1 denotes a cyano group; an intermediate compound of general formula where Bx is as described above; R1 is a substitute of general formula (2); an intermediate compound of general formula where Bx is as described above; A is a silicon-containing substitute of general formula or where R6 denotes alkyl and WG1 denotes a cyano group. The invention also relates to a method of producing an oligonucleotide of general formula where each B independently denotes adenine, guanine, cytosine, uracil or thymine; each R independently denotes H or hydroxyl and at least one of R denotes hydroxyl; Z denotes H or a phosphate group; and n is an integer between 1 and 100, involving steps A-G, characterised by use of said phosphoramidite derivatives as a monomer compound of nucleic acid at step B.

EFFECT: high yield.

7 cl, 1 dwg, 21 ex

Up!