Derivatives (2-imidazolin-2-yl) thieno or furo(3,2-c) pyridine carboxylic acid herbicide composition, the ingredients for their production

 

(57) Abstract:

Usage: agriculture, chemical means of plant protection. The essence of the invention: derivatives (2-imidazolin-2-yl) thieno or furo [3,2-b] pyridine, f-crystals I mentioned in the text of the description, in which a single or double bond, R1and R2WITH1-C4-alkyl, A-CO2R3where R3is hydrogen, C1-C4-alkyl,

methylphenyl,3-C4-alkyl, C3-C4-quinil, NH3CH3(CH3)2B is hydrogen, W is oxygen, sulfur or > S=O, Y is hydrogen, C1-C4-alkyl, halogen, phenyl, Y is hydrogen, Z is hydrogen, C1-C4-alkyl, hydroxy, nitro-group, WITH1-C4-alkoxy, Z is hydrogen, methyl. Y and Z may together form a ring including the chain -(CH2)4and when R1- R2unequal their optical isomers, except for the case when R3-salt-forming cation, herbicide composition and ingredients for their production. 5 C. p. F.-ly, 2 tab.

The invention relates to new 2-imidazolin-2-yl)thieno - foroperational compounds, to intermediates used to obtain these compounds, and the way of dealing with these compounds with niela the-2-yl)thieno - and furo[3,2-b]pyridine compounds and the corresponding 2,3-dihydrothieno and 2,3-dihydropyrimidine with structural formulas (Ia) and (Ib):

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where is a single or double bond; R1represents a C1-C4alkyl; R2represents a C1-C4alkyl or C3-C6cycloalkyl; R1and R2together with the carbon atom to which they are joined, can form WITH3-C6cycloalkyl, optionally substituted stands; And represents R3CHO, CH2OH, COCH2HE, CONHCH2CH2OH, CONHOH or

R3hydrogen, C1-C12alkyl, which can be broken by one or more oxygen atoms or sulfur and optionally substituted by one of the following groups:1-C3alkoxy, halogen, hydroxyl, C3-C6cycloalkyl, benzyloxy, fullam, phenyl, furfuryl, galopera, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyla, lower alkoxycarbonyl, cyano, C1-C4alkylthio or three (lower) alkylammonium; C3-C6alkenyl, optionally substituted by one of the following groups:1-C3alkoxy, phenyl, halogen or two WITH1-C3alkoxygroup or two halogen groups; C3-C6cyclooctyl, optionally substituted by one or two12IT; or the cation of an alkali metal or alkaline-earth metal (CA, BA) manganese, copper, iron, ammonium, or organic ammonium; RWITHand RDrepresent N or CH3; Represents N; COR4or SO2R5provided that when a represents a COR4or SO2R5and is a OOR3the radical R3cannot be hydrogen or a salt-forming cation; R4represents a C1-C11alkyl, chloromethyl or phenyl, optionally substituted by one chloro-, one nitro, one methyl, or one methoxy group; R5represents a C1-C5alkyl or phenyl, optionally substituted one metalno, chloro - or nitro-group; W represents 0 or S; X represents 0, S or when is a single bond, the group S 0; Y and Y', Z and Z' represent hydrogen, halogen, C1-C6alkyl, C1-C4hydroxy (lower) alkyl, C1-C6alkoxy, C1-C6acyloxy, benzoyloxy, optionally substituted by one or two1-C4alkyl, C1-C4alkoxygroup or halogen; C1-C4alkylthio, phenoxy,1-C4haloalkyl,1- 4alkylsulfonyl or phenyl, optionally substituted by one or more1-C4the alkyl, C1-C4alkoxy, halogen, or any combination of these two groups, where Y and Z are the same provided that Y and Z represent hydrogen, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are the same group they are hydrogen or alkyl; and taken together, Y and Z form a ring in which YZ has the structural formula -(CH2)n- where n is an integer selected from 3 and 4; or

-= -= where L, M, Q, and R7each represent hydrogen, halogen, nitro, C1-C4lower alkyl, C1-C4lower alkoxy, methoxy, phenyl, phenoxy, provided that only one of the radicals L, M, Q or R7may have a value different from hydrogen, halogen, C1-C4the alkyl or C1-C4alkoxy; or a pyridine-N-oxides, when W represents oxygen or sulfur and a is COOR3; and when R1and R2not the same, the optical isomers of these compounds, except for the case when R3represents a salt-forming cation, kislotoustoichivam salts.

A preferred group of 6-(2-imidazolin-2-yl)thieno-what Yu like (Ia) and (Ib), where R1represents methyl; R2represents methyl, ethyl, propyl, isopropyl, or taken Veste form tsiklogeksilnogo or methylcyclohexane ring; W represents an oxygen or sulphur; represents hydrogen; represents COOR3where R3has videopreteen values; Y and Z represent hydrogen, C1-C3alkyl, C1-C3alkoxy, alkylthio, halo, nitro, cyano, trifluoromethyl, MonitorMaster, deformity, monitorless, deformedarse, triptoreline, methylsulphonyl, methyl - sulfonamide, methylamino, dimethylamino or isopropylamino, when Y and Z together, they form the group-(CH2)3, -(CH2)4or-CH=CH-CH=CH-.

The most preferred (2-imidazolin-2-yl) thieno and furosemidee formulas (Ia) and (Ib) are those compounds in which a represents a hydrogen, Y and Z represent hydrogen, chloro, methyl or methoxy, provided that one of the radicals Y or Z represents hydrogen; W is an oxygen; And represents COOR3where R3represents hydrogen, furfuryl, PROPYNYL,3-haloalkyl, Na+or isopropanolamine, and R1and R2have the hat is hydrogen, imidazolylidene-, furo[2,3-b] and [3,2-b]pyridine formulas (Ia) and (Ib) may exist as tautomers. Although for convenience they represent a single structural formulas (Ia) and (Ib), they can exist in any of the illustrated by the following tautomeric forms:

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Assumes that both tautomeric forms are described by formulas (Ia) and (Ib).

The invention also relates to new substituted thieno - and furosemidepropranolol compounds of formulas (IIa) and (IIb) and the way of dealing with these compounds with unwanted annual and perennial plants in crops of soya cultural and some cereals:

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where X, Y, Y', Z, Z', W, R1and R2have listed for formulae (Ia) and (Ib) values, where X, Y, Z, W, R1and R2in the preferred and most preferred compounds of the formulas (IIa) and (IIb) have the meanings given for the preferred and most preferred compounds of formulas (Ia) and (Ib).

Which herbicides substituted pyridine and quinoline-2-imidazolin-2-sludge acids, esters and salts are known. The invention relates to new thieno - and furo[2,3-b]pyridinium and thieno - and furo[3,2-b]pyridinium, which being substituted in the 6 or 5 position of the imidazoline to the on - and-properidine give strong herbicides, is unexpected, since in the literature there is no indication that such [2,3-b] or [3,2-b] cyclic system can be used for agronomic purposes or as herbicides. This new class of herbicides are very effective in pre - and post-harvest processing, and some representatives of this class of compounds exhibit unusual selectivity in crops of soya cultural and grain crops such as wheat, oats, rice, rye and barley. In addition, it was found that the selectivity to crops can be enhanced, And when is a CO2N, by obtaining esters, in particular furfuryl, alkinilovymi and haloalkylthio ethers.

In addition, some compounds of this class are unexpected astragulus effects on plants, reduce the height of it, increased tillering and resist lodging of crops.

Compounds of the invention can conveniently be obtained from an appropriately substituted thieno - and furo[2,3-b] and [3,2-b]pyridinecarboxylic acids and esters of the formula (IIIa) and (IIIb):

and

where X, Y and Z have defined meanings and R represents methyl or ethyl.

Methods of obtaining new meningialnyh acids of formulas (IIIa) and (IIIb) are illustrated in technological scheme I, below.

So, esters of dibasic acids of the formula (IIIa) and (IIIb) can be subjected to hydrolysis to the corresponding Taino - and furo-2,3-pyridinedicarboxylic acids of the formulas (IVa) and (IVb), by reaction with a strong base, such as potassium hydroxide or sodium hydroxide. The acid anhydrides of the formulae (Va) and (Vb) can then be obtained by processing pyridineboronic acids of the formulas (IVa) and (IVb), for example, acetic anhydride. In the reaction of anhydrides of formula (Va) and (Vb) with an appropriately substituted aminocarboxylic or iminodicarboxylic formula (VI) receive carbamoylation acid of formula (VIIa) and (VIIb). The processing thus obtained carbamodithioic acid aqueous or aqueous-alcoholic solution of sodium hydroxide or potassium in an amount of 2 to 10 equivalents, preferably under an inert gas, such as nitrogen, cooling and acidification to pH 2-4 with a strong mineral acid, such as hydrochloric or sulfuric, get herbicide effective 6-(4,4-disubstituted-5-oxo- (or thioxo)-2-imidazolin-2-yl)thieno - and furo[2,3-b]pyridine-5-carboxylic acid and 5-(4,4-disubstituted-5-oxo-(or thioxo)-2-imidazolin-2-yl)thieno - and furo[3,2-b]pyridine-6-carboxylic acid, to the Ira formula (Ia) and (Ib), where a represents a COOR3and R3Deputy other than hydrogen and Kolobrzeg cation, and R1, R2X, Y and Z have defined meanings, can be obtained by interaction of new thieno - or durominenoprescription1o formulas (IIa) and (IIb) (below presents the flowsheet II) with a suitable alcohol and the corresponding alcoholate of an alkali metal at a temperature of from 20 to 50aboutC.

New thieno - and furosemidepropranolol formulas (IIa) and (IIb) can be obtained from the acids of formulas (Ia) and (Ib), where a represents hydrogen, by treatment with one equivalent dicyclohexylcarbodiimide in an inert solvent such as methylene chloride, as illustrated by the flowsheet II.

Technological scheme I

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Technological scheme II

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where M1alkali metal and X, Y, Z, R1, R2and R3have certain values.

Many thieno [2,3-b] pyridinecarboxamide acid of formula (IIIa) and thieno [3,2-b] pyridinecarboxamide acid of formula (IIIb) can be conveniently obtained by reaction of the appropriately substituted 2 - or 3-aminothiophene formula (VIIIa) or (VIIIb), where R is presented is rmula (IX), as described Bleckert et al. Chem. Ber. 1978, , 368. Thus obtained complex-aminothieno- , -unsaturated ester of formula (X) is then injected into interaction with the ammonium salt of the formula

Cl-CH N-(R)2Clwhere R"' represents a C1-C6alkyl or Cl-CH (CH2)l, where n' is 4 or 5, in the presence of chlorine substituted hydrocarbon solvent with a low boiling point, such as methylene chloride or dichloroethane, at a temperature of 40-90aboutWith over a period of time sufficient for almost complete reaction, resulting in a gain [2,3-b]thieno - or [3,2-b]thieno-2,3-pyridinedicarboxylate acid of formula (IIIa) or (IIIb), respectively, in the form of dialkylamide of ester, as shown in process scheme III.

Furo [3,2-b] pyridinecarboxamide acid of formula (IIIb) can be obtained by reaction of 3-amino-2-formylfuran formula (XI) obtained by the method of S. Gronowitz et al. Acta Chemica Scanol V 224 (1975), with ethylacetoacetate, resulting immediately receive properidine the compounds of formula (IIIb), as shown in the flowsheet IV, while furo[2,3-b]pyridine compounds, where Y and Z represent hydrogen, produced by the synthesized reaction product (XII) is orovided sodium and paratoluenesulfonyl heated to the temperature of reflux distilled xylene, as shown in the flowsheet V.

2,3-dihydrofuro [3,2-b] thieno [3,2-b] pyridine formula (Vb) can be obtained by the reaction of diethylethylenediamine with a mixture of enamines obtained from 3-ketterhagen or 3-betterregulation with subsequent treatment with ammonia or ammonium, as shown in process scheme VI.

Technological scheme III

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Technological scheme IV

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Technological scheme V

CH

Technological scheme VI

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where each of R1and R2represents a C1-C6alkyl, or taken together with the nitrogen atom to which they are bound, form a 5 - or 6-membered saturated heterocyclic ring, optionally containing up to 2 heteroatoms.

Furo [2,3-b] pyridine compounds of formula (IIIa), where Z represents hydrogen and Y represents alkyl or optionally substituted phenyl, get in the reaction of acetylene compounds with iodopyridine ester, dibasic acid (VII) (obtaining the compounds of formula VII described in J. Prakt.Chem. 148, 72 (1937), in the presence of copper salts, amine base and a palladium catalyst (II), as shown in process scheme VII.

or

S H H CH3S H Br CH3S CH3H CH3S H Cl CH3S Cl Cl CH3S H I CH3S H NO2CH3S Br Br CH3S CH3Cl CH3S H CH3CH3S Cl H CH3S CH3CH3CH3S H CN CH3S H OCH3CH3S H N(CH3)2CH3S H SCH3CH3S H OCF2H CH3O H H C2H5O H Br CH3O H Br C2H5O H Cl CH3O H Cl C2H5O CH3HB>3O CH3CH3CH3S -(CH2)3- CH3S -(CH2)4- CH3S -(CH)4- CH3S C6H5H CH3O C6H5H CH3S H SO2N CH3S H OC6H5CH3< / BR>
O H OC6H5CH3O CF3H CH3O H NO2C2H5O Br Br C2H5O H C6H5S C2H5O H CF3C2H5< / BR>
In addition, new herbicide active 2,3-dihydrothieno[2,3-b] and [3,2-b] pyridine compounds can be obtained according to the technological scheme III, based on dihydrothiophene hydrochloride. New herbicide active 2,3-dihydrofuro [2,3-b] and [3,2-b] pyridine can be obtained by catalytic reduction of 2-imidazolin-2-yl of the formula (Ia) or (Ib) or furo [2,3-b] and [3,2-b] pyridine-5,6-ether dibasic acids of the formula (IIIa) and (IIIb), for example, hydrogen in the presence of palladium on a substrate of activated carbon catalyst, provided that Y and Z are substituents that were not recovered by this procedure. Other 2,3-dihydrofuro[2,3-b] pyridine obtained by recovery of bromoketones with sodium borohydride followed by treatment with triethylamine and p-toluensulfonate, as shown in technologically advanced">

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where X, Y, Y', Z, Z', W, B, R1and R3have the value of specified for (Ia) and (Ib).

Technological scheme (VIII)

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6-(2-imidazolin-2-yl)thieno - and furo[2,3-b]pyridine and 5-(2-imidazolin-2-yl)thieno - and furo[3,2-b] pyridine formulas (Ia) and (Ib) and imidazopyridine formulas (IIa) and (IIb) of the invention are very effective herbicide preparations suitable for fighting with an exceptionally large variety of grassy weeds annual and perennial monocotyledonous and dicotyledonous plants. Moreover, these compounds are herbicide active to control weeds growing in both dry and wet areas. They are also useful for dealing with plants growing in the water, and exhibit exceptional activity in the suppression of these plants in the processing of their leaves or soil, or water, in which are the seeds of these plants or their reproductive organs, such as tubers, rhizomes or stolons, and the dose of a compound is 0,016-4.0 kg/ha, preferably 0,032-2.0 kg/ha For effective control of undesirable vegetation you can use the connection and the dose is higher than 4.0 kg/ha, however, the use of a toxicant at doses exceeding those necessary for unichtojennaya environment.

Using the proposed compounds can destroy the following plants:

Elatine triandra, Sagittaria pygmaea, Scirpus hotarui, Cyperus serotinus, Eclipta alba, Cyperus difformis, Rotala indica, Lindernia pyridoria, Echinochloa crus-galli, Digitaria sanguinalis, Setaria viridis, Cyperus rotundus, Convolvulus arvensis, Agropyron repens, Datura stramonium, Alopercurus myosuroides, Ipomoea spp. Siola spinosa, Ambrosia artemisiifolia, Eichhornia crassipes, Xanthium pensylvanicum, Sesbania exaltata, Avena fatua, Abutilon theophrasti, Bromus tectorum, Sorghum halepense, Lolium spp. Panicum dichotomiflorum, Matricaria spp. Amaranthus retroflexus, Cirsium arvense and Rumex iaponicus.

It was found that (2-imidazolin-2-yl)thieno - and properidine formulas (Ia) and (Ib) are selective herbicides, particularly effective for controlling undesirable vegetation in crops of leguminous plants such as soybean, and grain crops such as wheat, barley, oats and rye. However, some of the compounds of formulas (Ia) and (Ib) are less selective compared to other on these crops.

It was also discovered that some (2-imidazolin-2-yl)pyridine formulas (Ia) and (Ib) are effective compounds for combating lodging of cereal crops at the ava 0,016-4.0 kg/ha Was also found that when using the dose does not exceed 0,010 kg/ha some thieno - and properidine formulas (Ia) and (Ib) are effective to enhance tillering cereals and formed the(Ia) and (Ib) and their derivatives, in which R3represents a salt-forming cation, soluble in water, these compounds can easily dispersing in water and apply as a diluted water spray on the leaves of plants or the soil in which are their reproductive organs. These salts can also be prepared in the form of liquid concentrates.

(2-imidazolin-2-yl)thieno - and properidine formulas (Ia) and (Ib) and imidazopyridine formulas (IIa) and (IIb) can also be prepared in the form of wettable powders, flowable concentrates, mulgirigala concentrates, granules, etc.

Wettable powders can be obtained by joint grinding 20-45 wt. finely powdered carrier such as kaolin, bentonite, diatomaceous earth, attapulgite or the like, 45-80 wt. active connections, 2-5 wt. dispersing agents, such as sodium lignosulphonate and 2-5 wt. nonionic surfactants, such as octylphenoxypolyethoxyethanol, nonylphenolethoxylates or the like.

Typical fluid can be obtained by mixing 40 wt. active ingredient with 2 wt. the gelatinization agent, such as bentonite, 3 wt. dispersing agent such as sodium lignosulfonate, 1 wt. of polyethylene glycol and 54 wt. water.

If compounds of the invention are expected to be used as a soil herbicides, they can be prepared and used in the form of granules. Preparation of the granulated product can be accomplished by dissolving the active compound in a solvent such as methylene chloride, N is an organic or the like, spraying the thus obtained solution of granular media, such as ground corn cobs, sand, attapulgite, kaolin or the like.

Thus obtained granulated product usually contains 3-20 wt. the active ingredient and 97-80 wt. granular media.

To illustrate the invention, examples that do not limit, but only illustrate it.

P R I m e R 1. Getting dimethylthieno[3,2-b]pyridine-5,6-in primary forms.

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A mixture of isopropyl-3-thiophenecarboxylate (177 g, 0,975 mol) in methanol (1.2 l) and water (2.8 l), containing Giulini and the cooled reaction mixture was extracted with simple diethyl ether (5 l), the extracts were washed with water, aqueous sodium chloride and dried. After evaporation under reduced pressure received 3-aminothiophene in the form of oil, crude yield 57% 3-Aminothiophene re-dissolved in methanol (500 ml), cooled in an ice bath and added dropwise to the mixture was added diethylazodicarboxylate (80 g, 0.50 mol). The mixture was stirred at room temperature for 15 h and 30 min, the methanol was distilled under reduced pressure and added 1,2-dichloroethane. This solvent also drove and got dimethyl-3-tanyametelya in the form of oil. The reagent Vilsmeier prepared by adding dropwise with stirring phosphorus oxychloride (86 g of 0.56 mol) in chilled (5oC) a solution of dimethylformamide (41 g of 0.56 mol) in 1,2-dichloroethane (200 ml). This reagent was stirred at room temperature for one hour and 40 minutes, was diluted with 1,2-dichloroethane (100 ml), cooled to 5aboutWith, and then specified complicated dimethyl ether, dissolved in 1,2-dichloroethane (400 ml) was added to the reagent Vilsmeier dropwise at a temperature of 5aboutWith over 25 minutes the reaction Temperature was raised to room for 15 minutes, then to the temperature of reflux distilled within the next 2 hours and 25 minutes the Cooled reaction mixture was chromatographically is] pyridine-5,6-in primary forms, so pl. 124-125,5aboutC. Received a second fraction with so pl. 121-124aboutWith a total output of isopropyl-3-thiophenecarboxylate 19%

In this procedure, substituting isopropyl-3-aminodiphenylamine appropriately substituted aminothiophenol obtained the following compounds:

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P R I m m e R 2. Getting dimethylthieno [3,2-b]pyridine-5,6-in primary forms

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In concentrated sulfuric acid (170 ml), stir at room temperature, was added in parts of 3-acetylamino-2-formylthiophene (17.5 g, 0,103 mol). The mixture was heated at a temperature of 50aboutC for 30 min, cooled and poured into a mixture of ice water. The mixture was neutralized with excess amount of sodium acetate and was extracted from a simple diethyl ether (1 x 2 ml). The organic layer was obezvozhivani over anhydrous Na2SO4and drove, having a dark red resin that represents 3-amino-2-formylthiophene. The solution diethylazodicarboxylate (DMAD) (13 ml) in a mixture of acetic acid (5 ml), piperidine (5 ml), methylene chloride (100 ml) and toluene (100 ml) was added 3-amino-2-formylthiophene and the whole mixture was stirred over night. Methylene chloride was distilled and then the mixture was heated at the temperature of reflux distilled within 24 hours the Mixture hladilnata the mixture has stood for 60 min at room temperature, the solvent was distilled and using chromatography got dimethylthieno[3,2-b]pyridine-5,6-in primary forms, using as eluent a mixture of hexane with ethyl acetate, so pl. 124-125aboutC.

P R I m e R 3. Getting dimethyl-3-chloro[3,2-b]pyridine-5,6-in primary forms and dimethyl-2,3-dichlorethene[3,2-b]pyridine-5, 6-in primary forms

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The solution dimethylthieno [3,2-b] pyridine-5,6-in primary forms (15 g, 0,0525 mol) in a mixture of acetic acid (680 ml) and sodium acetate (86 g, 0,093 mol) maintained at a temperature of 58aboutWith, at the same time for 5 h 45 min slow feeding chlorine. After completion of the reaction the mixture was repaid by nitrogen, was added ethyl acetate (200 ml), filtered, solid sodium chloride and was washed with ethyl acetate. The mother liquor and washes were combined and the solvent was distilled under reduced pressure. The residue was dissolved in methylenchloride, the solution was washed with water, was subjected to reverse extraction with methylene chloride, the combined methylenchloride layers washed aqueous sodium bicarbonate, obezbedili and drove, obtaining 18 g of solid substance. After chromatography on silica gel using 15% ethyl acetate-hexane, then 20% of ETHYLACETYLENE got 2,3-dichloroethane, etc., 173-178aboutWith 1.3 g, and then after Krista is their dimethyl-3-bratiano [3,2-b] pyridine-5,6-dicarboxylate.

Br

A solution of bromine (20 g, 0.125 mol) in acetic acid (50 ml) dropwise over 3 h was added to the solution dimethylthieno[3,2-b]pyridine-5,6-in primary forms (26,3 g, 0.104 g mol) containing sodium acetate (17,2 g, 0.2 mol) in acetic acid (300 ml) at a temperature of 85aboutC. an Additional quantity of a solution of sodium acetate (18 g) and bromine (20 g) in acetic acid (50 ml) was added within 1 h, the mixture was stirred at a temperature of 85aboutWith during the night. To the mixture at once added bromine (10 g) and then left the mixture for 4 hours the Mixture is cooled, treated with aqueous sodium bisulfite, diluted with ethyl acetate and concentrated. The reaction product was separated into water and methylenchloride layers and the organic layer washed aqueous sodium chloride and drove the solvent. The residue is washed simple diethyl ether and received 25 g of raw product, so pl. 165-168aboutC. After recrystallization from methanol has been dimethyl-3-bratiano[3,2-b]pyridine-5,6-in primary forms in the form of needles, so pl. 168-OS.

P R I m e R 5. Getting thieno[3,2-b]pyridine-5,6-dicarboxylic acid.

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Dimethylthieno[3,2-b] pyridine-5,6-in primary forms (3.75 g, 0,0149 mol) was added into a solution of sodium hydroxide (1.8 g, 0.045 mol) in water (20 ml) and the mixture was heated feast temperature 60aboutS. T. pl. OS H H >380 H Cl did not take H Br >380 H I H F H CN H OCH3H NO2H N(CH3)2CH3 H H CH3CH3 CH3H OCHF2H SCH3H SO2N(CH3)2< / BR>
C6H5 H -(CH2)3- -(CH2)4- -(CH)4- Cl Cl H C6H5C6H5H H OC6H5CF3H C2H5H H C2H5H SC6H5H CF3H CHO H CH2Cl

Using the above procedure and appropriately substituted esters of dibasic thieno[3,2-b]pyridine-5,6-dicarboxylic acid, obtained the following compounds:

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P R I m e R 6. Getting anhydride 3-chlorothieno[3,2-b] pyridine-5,6-dicarboxylic acid.

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3-Chlorothieno [3,2-b] pyridine-5,6-dicarboxylic acid (1.45 g) was heated from 85 to 90aboutC for 30 min and then from 90 to 102aboutC for 30 min in acetic anhydride (7 ml). The mixture was cooled, the solids were filtered, washed simple diethyl ether and obtained 1.2 g of anhydride 3-chlorothieno[3,2-b] pyridine-5,6-dicarboxylic acid. Range TMR corresponds to the structural formula.

Using ukazanno theH H 266-267 H Cl Solid ve-

the society i.e. not received H Br >380 Cl H Cl Cl H NO2CH3H H N(CH3)2H SCH3H JCH3H CH3H F H I CH3CH3H CN H OCHF2H SO2N(CH3)2-(CH2)3- -(CH2)4- -(CH)4- H C6H5C6H5H H OS6H5CF3H C2H5H H C2H5H SC6H5< / BR>
H CF3H CHO H CH2Cl

P R I m e R 7. Getting 5-(1-carbarnoyl-1,2-dimethylpropyl)-3-chlorothieno[3,2-b]PI - ridin-6-carboxylic acid.

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2-Amino-2,3-dimethylbutyramide (0.71 g) in one step added in the mixed solution of the anhydride of 3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid (1.2 g) in THF (1.0 ml). After 5 min the ice bath was removed and the reaction mixture was stirred at room temperature for 28 hours and Then added a THF (5 ml), the mixture was heated at the temperature of reflux distilled for 2 h and then left overnight. The cooled mixture was filtered and the collected solids washed simple diethyl ether, having obtained 1.4 g of the desired 5-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl] -3 - chlorothieno[3,2-b]pyridine-6-carboxylic acid.

According to the described method, instead of using anhydride 3-chlorothieno[3,2-b]pyridine-5, which had the following connections:

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So pl.aboutWITH

H H CH3i-C3H7< / BR>
H Cl CH3i-C3H7not clean

Cl H CH3i-C3H7< / BR>
Cl Cl CH3i-C3H7< / BR>
H Br CH3i-C3H7< / BR>
H CN3CH3i-C3H7< / BR>
H NO2CH3i-C3H7< / BR>
H N(CH3)2CH3i-C3H7< / BR>
H SCH3CH3i-C3H7< / BR>
H OCH3CH3i-C3H7< / BR>
CH3H CH3i-C3H7< / BR>
H H CH3C3H7< / BR>
H H CH3C2H5< / BR>
H OCHF2CH3i-C3H7< / BR>
CH3CH3CH3i-C3H7< / BR>
H CN CH3i-C3H7< / BR>
H F CH3i-C3H7< / BR>
H I CH3i-C3H7< / BR>
H SO2N(CH3)2CH3i-C3H7< / BR>
C6H5H CH3i-C3H7< / BR>
-(CH2)3- CH3i-C3H7< / BR>
-(CH2)4- CH3i-C3H7< / BR>
-(CH)4- CH3i-C3H7< / BR>
H C6H5CH3i-C3H7< / BR>
C2H5H CH3i-C3H7< / BR>
H OC6H5CH3i-C3H7< / BR>
H CH2Cl CH3
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H CHO CH3i-C3H7< / BR>
H CF3CH3i-C3H7< / BR>
H SC6H5CH3i-C3H7< / BR>
P R I m e R 8. Getting 5-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) thieno [3,2-b] pyridine-6-carboxylic acid.

< / BR>
Thieno [3,2-b] pyridine-5,6-dicarboxylic acid (2.5 g, to 0.011 mol) was slowly heated to a temperature of 85aboutC for 1 h with acetic anhydride (25 ml), then cooled, filtered, washed simple diethyl ether and received anhydride in the form of a solid substance with so pl. 266-267aboutC. the Mixture of anhydride and 2-amino-2,3-dimethylbutyramide (2.6 g, 0.02 mol) in THF (70 ml) was stirred at room temperature for 15 hours, the Mixture was heated at the temperature of reflux distilled for 2 h, then cooled and diluted with THF (50 ml). Solid 5-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl]thieno [3,2-b] pyridine-6-carboxylic acid was filtered, washed simple diethyl ether and obezbedili. Specified, the solid was mixed with anhydrous (60 ml) solution of sodium hydroxide (6 g, 0.05 mol) and was heated at a temperature of 85aboutC for 2.5 h and then left at room temperature overnight. The mixture was cooled in an ice bath and acidified to pH 3 with concentrated hydrochloric acid. what-methyl-4-oxo-2-imidazolin-2-yl)thieno[3,2-b] pyridine-6-carboxylic acid, so pl. 242-244aboutFrom exit 46%

In this procedure, instead of using thieno[3,2-b] pyridine-5,6-dicarboxylic acid corresponding pyridine-5,6-dicarboxylic acid, obtained the following compounds:

H H 242-244 H Cl 238-239 H Br Cl 226-227 of H 247-248 Cl Cl H CH3CH3H H NO2H N(CH3)2H SC6H5H SCH3H OCH3H OCHF2CH3CH3H CH H SO2N(CH3)2C6H5H

-(CH2)3-

-(CH2)4-

-(CH2)4- H C6H5H OC6H5CF3H C2H5H H C2H5H I H F H CHO H CH2Cl H CF3< / BR>
P R I m e R 9. Getting diterpene[3,2-b]pyridine-5,6-in primary forms

____< / BR>
3-Amino-2-formylfuran obtained from 3-azido-2-formylfuran (8,9 g 0,065 mol), dissolved in ethanol and this solution was added diethyloxalate (12,23 g 0,065 mol) and 10 drops of piperidine. In addition, the added sprayed molecular sieves 3, the reaction mixture was stirred at a temperature 65-60aboutC for 3 h and then added more diethyloxalate (2.2 g). The reaction is practically completed after 12 h at a temperature of 55-60aboutC. After cooling, the reaction mixture was filtered, the filtrate scancenter and dry. The residue was dissolved in a mixture of hexane-ethyl acetate (3:1) and in two stages pass through evaporative chromatographic column. First, the mixture using a vacuum was filtered through a 4-5 inch strip of silicon dioxide, then the last three fractions containing the desired product were collected and combined. These combined fractions skipped through the 6-inch column, elwira pressurized mixtures of ethyl acetate hexane 3:1 and 2:1. After crystallization from a mixture of hexane-simple diethyl ether got diterpene [3,2-b] pyridine-5,6-in primary forms, 4.15 g (24% ), so pl. 60-64aboutWith the data of the mass spectrograph; m/e 264.

Using this method and the corresponding furan instead of 3-amino-2-formylfuran obtained the following compounds:

H H CH560-64 H Cl C2H5CH3H C2H5H CH3C2H5C2H5H C2H5H C2H5C2H5CH3CH3C2H5< / BR>
P R I m e R 10. Getting furo [3,2-b]pyridine-5,6-dicarboxylic acid.

< / BR>
Complex diethyl ether furo[3,2-b]pyridine-5,6-dicarboxylic acid (1.1 g, 0,0042 mol) was dissolved in 95% ethanol (20 ml) containing 10% aqueous solution of sodium hydroxide (20 ml) and left at Temperley. Added 5 ml of water and after filtering received dibasic gidratirovannuyu acid as a brown solid substance, of 3.31 g (99%), so pl. 183aboutC (decomposes).

Analysis for C9H5NO52 1/2 H2O

Calculated WITH 42,86; N 3,99; N 5,55

Found, 42,63; N 2,63; N 5,46

Using the described procedure and the corresponding esters furo[3,2-b] pyridine-5,6-dicarboxylic acid, obtained the following compounds: H H H 183 (decomposition) H Cl C2H5CH3H C2H5H CH3C2H5C2H5H C2H5H C2H5C2H5CH3CH3C2H5< / BR>
P R I m e R 11. Getting anhydride furo[3,2-b]pyridine-5,6-dicarboxylic acid.

< / BR>
A solution of furo[3,2-b]pyridine-5,6-dicarboxylic acid (3.3 g, 0,0159 mol) in acetic anhydride (100 ml) was heated at a temperature of 70-80aboutC for 6 hours, the Reaction mixture was cooled, filtered, the solids washed simple diethyl ether and received a 3.01 g (100%) of the crude anhydride furo [3,2-b] pyridine-5,6-dicarboxylic acid.

In this procedure using the corresponding furo [3,2-b] pyridine-5,6-dicarboxylic acid, obtained the following compounds:

< / BR>
H H

H ClP R I m e R 12. Getting 5-[(1-carbarnoyl-1,2-dimethylpropyl) carbarnoyl] furo[3,2-b] pyridine-6-carboxylic acid and 5-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) furo[3,2-b]pyridine-6-carboxylic acid.

< / BR>
Anhydride furo [3,2-b] pyridine-5,6-dicarboxylic acid (3,01 g, 0.015 mol) is suspended in tetrahydrofuran (100 ml) to which was added 2-amino-2,3-dimethylbutyramide (2.3 g, 0.018 mol). The mixture was stirred for 20 h, then drove to obtain an oily solid, which is dissolved in a mixture of water with dilute sodium hydroxide solution. The alkaline solution was extracted with methylene chloride, acidified, re was extracted with methylene chloride and stirring was allocated only traces of the substance. The aqueous layer was concentrated to obtain a solid oily substance, which was dissolved in ethanol, filtered and concentrated to a resin purple color, which mostly represents the crude product, 5-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl]furo [3,2-b]pyridine-6-carboxylic acid, which is used without further purification to obtain the target 2-imidazolin-2-Il by dissolving it in a 10% solution of sodium hydroxide (40 ml) and heating at a temperature of 80aboutWith in th filtered out. After concentration of the mother liquor obtained in the second fraction, which was collected and combined with the first fraction. Purification was carried out by taking half of the material and separated on preparative glass plates with silica gel layer. Slower current layer in the elution with a mixture of methylene chloride ethyl acetate, chloroform, methanol 1 1 1 1 gave the desired 2-imidazolin-2-yl, T. pl. 214-223aboutC (with decomposition). Esters can then be obtained using the procedure described in example 20.

Using the described procedure and the appropriate anhydride furo[3,2-b]pyridine-5,6-dicarboxylic acid, obtained the following compounds:

H H 214-223 (decomposition) H Cl CH3H H CH3C2H5H H C2H5CH3CH3< / BR>
P R I m e p 13. Getting dimethylthieno[2,3-b]pyridine-5,6-in primary forms.

< / BR>
The reagent Vilsmeier prepared by adding dropwise with stirring phosphorus oxychloride (40,29 g, 0.26 mol) in chilled (10aboutC) a solution of DMF (19,0 g, 0.26 mol) in 1,2-dichloroethane (40 ml) under nitrogen atmosphere. This reagent was stirred at room temperature for 1 hour and 45 minutes In the reagent Vilsmeier at a temperature of 7-10aboutWith dropwise added dimethyl-2-tanyametelya (and 63.4 g, 0.26 mol) temperature reflux distilled for 12 hours The cooled reaction mixture was concentrated, the residue was chromatographically on silica gel, using as eluent a mixture of ethyl acetate-hexane, and received dimethylthieno [2,3-b]pyridine-5,6-dicarboxylate (29 g, 45%) as a solid.

Using the described method and the corresponding dimethyl-2-tanyametelya obtained the following compounds:

CH3H 80-82 H H H 80-81 CH3CH3CH3H C6H5C6H5H CF3H

-(CH2)4- 118-121,5

P R I m e R 14. Getting dimethyl-3-bratiano [2,3-b]pyridine-5,6-in primary forms.

Br

A solution of bromine (0.33 g, 0,00206 mol) in acetic acid (8 ml) was added to stir the solution dimethylthieno [2,3-b]pyridine-5,6-in primary forms (0.5 g, 0,00187 mol) in acetic acid containing sodium acetate (0.31 g, 0,00377 mol) at a temperature of 40aboutC. the Reaction mixture was heated at a temperature of 75aboutC for 18 hours the mixture Analysis by TLC (silica gel) showed that the reaction was not completed. Added an additional quantity of a solution of bromine (0.33 g) in acetic acid and sodium acetate (0.31 g) and heated at a temperature of 75aboutWith continued for 6 hours, the Reaction mixture was diluted with water and extracted with ethyl acetate. Ameerali to obtain oil, which, when the shutter speed is solidified. After crystallization of the crude product from a mixture of ethyl acetate with hexane got dimethyl-3-bratiano [2,3-b] pyridine-5,6-in primary forms, in the form of white needles, so pl. 86-87,5aboutC.

This connection can easily be turned into a series of substituted thieno [2,3-b] pyridine compounds, as shown below, and electrophilic substitution, such as nitration or gorodilova, allow to obtain the following additional connections:

H H H Cl 104-110 H Br 86-87,5 H I H F H CN H SCH3H OCH3H N(CH3)2H OCHF2H NO2H CHO H CH2Cl CH3H 80-82 H CH3oil Cl H Cl Cl 84-89 CH3CH3H SO2N(CH3)2-(CH2)4- 118,5-121,5 -(CH)4- -(CH2)3< / BR>
C6H5H H C6H5H OC6H5CF3H SC H6H5H CF3C2H5H H C2H5< / BR>
P R I m e R 15. Getting thieno[2,3-b]pyridine-5,6-dicarboxylic acid.

< / BR>
The solution dimethylthieno [2,3-b] pyridine-5,6-in primary forms (27,75 g, 0.11 mol) and potassium hydroxide (30,98 g, 0.55 mol) in methanol (200 ml) was heated in nitrogen atmosphere at the temperature of reflux distilled for 2 hours, the Reaction mixture was cooled, added water in an amount sufficient to rustikalnom volume of water, cooled in an ice bath and was acidified with concentrated sulfuric acid to pH 1. Thieno[2,3-b] pyridine-5,6-dicarboxylic acid was filtered and dried over night, having 23,36 g of substance with so pl. 272-275aboutC.

Using the described methodology and appropriately substituted dialkylamino[2,3-b]pyridine-5,6-in primary forms, obtained the following compounds:

H H 272-275 H Cl >300 H Br >315 H I H F H CN H SCH3H OCH3H N(CH3)2H OCHF2H NO2H CHO H CH2Cl H CH3180-183

(Razlog. ) CH3H Cl H Cl Cl CH3CH3C6H5H H SO2N(CH3) -(CH2)3- -(CH2)4- 280-290 -(CH)4H OC6H5H C6H5CF3H H CF3H SC6H5C2H5H H C2H5< / BR>
P R I m e R 16. Getting anhydride thieno[2,3-b]pyridine-5,6-dicarboxylic acid.

< / BR>
Acetic anhydride (or 37.4 g, 0,366 mol) was added to stirred suspension of thieno[2,3-b]pyridine-5,6-dicarboxylic acid (21,52 g 0,096 mol) in dimethoxyethane (175 mol) in an inert nitrogen atmosphere. Adding pyridine (16.78 in g, 0.21 mol) at room temperature was observed to increase the temperature to 45aboutWith the result of the exothermic reaction and belgae substance was filtered, washed simple diethyl ether, dried on air and got 14.8 g (75%) of the anhydride thieno[2,3-b]pyridine-5,6-dicarboxylic acid.

According to the described method, using the appropriately substituted thieno[2,3-b]pyridine-5,6-dicarboxylic acid, obtained the following compounds:

CH3H 176-180 H Br 228,5-231 H Cl 230-300

(slow

Razlog.) H H 210-213 H I H F H CN H SCH3H N(CH3)2H NO2H CHO H CH2Cl H CH3Cl H Cl Cl CH3CH3C6H5H H SO2N(CH3)2-(CH2)3- -(CH2)4- 220-222

-(CH)4- H C6H5H OC6H5CF3H H CF3H OCHF2H SC6H5H OCH3C2H5H H C2H5< / BR>
< / BR>
P R I m e R 17. Obtain 6-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl] thieno[2,3-b]pyridine-5-carboxylic acid.

< / BR>
2-Amino-2,3-dimethylbutyramide (9,84 g, 0,076 mol) was added to stirred suspension of the anhydride thieno [2,3-b]pyridine-5,6-dicarboxylic acid (14.8 g, 0,072 mol) in THF in an inert atmosphere of nitrogen at room temperature. The dark solution was stirred at room temperature overnight, the resulting solid substance was filtered, washed THF, dried on air and got of 17.35 g (72%) of 6-[the ICA, using appropriately substituted anhydrides thieno[2,3-b] pyridine-5,6-dicarboxylic acid, obtained the following compounds:

CH3H 207-208 H Br 176-178 H Cl 156-158 H H H I H F H CN H SCH3H OCH3H N(CH3)2H NO2H CHO H CH2Cl H CH3Cl H Cl Cl CH3CH3C6H5H H SO2N(CH3)2-(CH2)3- -(CH2)4- solid substances.

-(CH)4- H C6H5H OC6H5CF3H H OCHF2H CF3H SC6H5C2H5H H C2H5< / BR>
P R I m e R 18. Obtain 6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)tie - but[2,3-b]pyridine-5-carboxylic acid.

< / BR>
6-[(1-Carbarnoyl-1,2-dimethylpropyl)CT - bemail] thieno[2,3-b] pyridine-5-carboxylic acid (of 17.35 g, 0,052 mol) was added in water (225 ml) containing sodium hydroxide (10,35 g, 0.26 mol). Obtained the basic solution was heated at a temperature of 80aboutC for 2 h 45 min, cooled in a bath of water and ice and acidified with 6 N. sulfuric acid. The obtained 6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carbon of voukelatos was filtered, washed with water, dried on air and got 1.54 g (70.3 per cent) substance so pl. 221-223aboutC.

P R I m e R 19. Getting 2-and what'or dicyclohexylcarbodiimide (1.07 g, of 0.005 mol) in methylene chloride (20 ml) was dropwise added into the mix methylenechloride (30 ml) suspension of 6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) thieno[2,3-b] -5-carboxylic acid (1.5 g, 0,0047 mol) in nitrogen atmosphere. The reaction mixture was stirred for 16 h, was filtered, concentrated to dryness and the resulting material was purified by chromatography on silica gel, using as eluent a mixture of acetonitrile-methylene chloride (1:2). The solid was subjected to crystallization from toluene and received net 3,5-dione as white crystals, so pl. 214,5-216,5aboutC.

P R I m e R 20. Getting 2-PROPYNYL-6-(5-isopropyl-5-methyl-4-oxo-2-imidazo - Lin-2-yl) thieno[2,3-b]pyridine-5-carboxylate.

< / BR>
Sodium hydride (2.4 g, 60% 0,126 mol) was added 3,5-dione (0.9 g, of 0.003 mol), dissolved in propargilovyh alcohol (25 ml) at a temperature of 10aboutWith in an inert atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 60 h and then neutralized with saturated solution of ammonium chloride. The resulting mixture was concentrated on a rotary evaporator, diluted with water and extracted with ethyl acetate. The organic layer was separated, obezbedili over anhydrous magnesium sulfate and concentraed acetonitrile 85:15) and got 2-PROPYNYL-6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2 - yl)pyridine-5-carboxylate, which after crystallization from toluene had so pl. 188-189,5aboutC.

According to the method of examples 18, 19 and 20, using the corresponding thieno [3,2-b] pyridine or thieno [2,3-b] pyridine obtained the following compounds:

So pl.aboutC H H CH3215-217 H H H 220-223.5(decomposition) H H-CH2CCH 188-189.5 H H 140-142 H H-CHH2108-110 CH3H H 225,5-227.5 H Br H 274-276 H Cl H 266-267 H NO2-CH3201-202.5oC H NO2H 260 (decomposition) Cl H H Cl Cl H H CH3H H N(CH3)2H H SCH3H H OCH3H H OCHF2H CH3CH3H H CN H H SO2N(CH3)2H C6H5H H H C6H5H

-(CH2)3- H

-(CH2)4- H

-(CH2)4- H H OC6H5H CF3H H C2H5H H H C2H5H H I H H F H H CHO H H CH2Cl H H CF3H SC H5H6H

H H H 242-244 H Cl H 238-239 H Br H H H 226-227 of 156-157 Cl H H 266-267 Cl I H H CH3H H F H CH3H H Cl Cl H H NO2H H N(CH3)2H H SCH3H H OCH3H CH3CH3H H CHO H H OCHF2H H CN H H SO2N(CH3)2H C6H5H H H C6H5H -(CH2)3- H -(CH2)4- H -(CH2)4- H H OC6H5H CF3H H H CF3H C2H5H H H C2H5H H CH2Cl H H SC6H5H

< / BR>

HNO3< / BR>
Methyl-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[2,3-b] pyridine-5-carboxylate (3.94 g, 0,0119 mol) was dissolved in 200 ml of concentrated sulfuric acid at room temperature. The reaction mixture was cooled to 3aboutC in an ice bath, while adding 1.5 ml (0,024 mol) of concentrated nitric acid. Then the mixture allowed to warm to room temperature. After 3 h the reaction mixture was poured into ice, neutralized with solid NaHCO3to pH 6 and extracted with methylene chloride. The extract was filtered, obezbedili over sodium sulfate, again was filtered, concentrated and the obtained solid yellow, 4,33 g (97%), which after crystallization from methanol-water had so pl. 201-202,5aboutC.

P R I m e R 22. Getting 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3 - nitration [2,3-b]pyridine-5-carboxylic acid.

< / BR>
Ester (1.0 g, 0,00266 mol) obtained in example 21 was mixed with a solution of 100 ml of methanol and 10 ml of 10% sodium hydroxide for 24 hours Then added water (25 ml) and the methanol was distilled in vacuum. The aqueous layer was acidified, resulting in dropped a brown precipitate, which was filtered, subjected to crystallization from a mixture of maindeck - barcelata.

CH3-

Sodium acetate was added to stir the mixture of diethyl (ethoxymethylene) oxalacetate (87 g, 0.36 mol) and acetoacetamide (36 g, 0.36 mol) in absolute ethanol (300 ml). The reaction mixture was stirred for 30 min, the ethanol was distilled under reduced pressure, the residue was acidified to pH 2 with dilute aqueous hydrochloric acid and the resulting solid was filtered. After crystallization from a mixture of ethanol-water received diethyl-5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinecarboxylic in the form of crystals with so pl. 101-110aboutC.

P R I m e R 24. Getting isobutyronitrile.

(CH

NaH (61,55 g of 60% dispersion, 1.54 mol) was added 650 ml of anhydrous THF under nitrogen atmosphere. The suspension was heated to the temperature of reflux distilled. Methylisobutyl (100 g, 98 mol) and acetonitrile (63,16 g, 1.54 mol) was mixed in 140 ml of anhydrous THF and added dropwise within 1 h was added heated to the temperature of reflux distilled suspension. The resulting solution was heated at the temperature of reflux distilled for 16 hours, the reaction mixture was added water in an amount sufficient to dissolve the salt formed. THF was distilled in vacuum, the basic aqueous solution was extracted with simple diethyl ether, then acidified using dcty was washed with brine, he obezbedili over anhydrous magnesium sulfate, was filtered, the solvent was distilled in vacuum and received 97,25 g (89.4 per cent) mentioned in the title product as an orange oil.

P R I m e R 25. Getting diethyl-5-(2-methylpropionyl)-1,6-dihydro-6-oxo-2,3-PI - reindeersexiest

(CH

Isobutylacetate (50 g, 0.45 mol) and diethyl (ethoxymethylene)-oxalacetate (110 g, 0.45 mol) was dissolved in absolute ethanol and added sodium acetate (36,9 g, 0.45 mol) and one drop of piperidine. After 12 h the mixture was concentrated, acidified with diluted hydrochloric acid and was extracted with methylene chloride. The extracts were concentrated, subjected to recrystallization and got listed in title product in the form of a solid white color, and 21.7 g (19.5 per cent), so pl. 116-118aboutC.

P R I m e R 26. Getting diethyl-5-(bromoacetyl)1,6-dihydro-6-oxo-2,3-pyridine - carboxylate

< / BR>
A solution of bromine (8.0 g, 0,050 mol) in 48% HBr dropwise added a mixed solution of diethyl-5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinecarboxylic - TA (14,05 g, 0.05 mol) in 48% HBr (200 ml). After complete addition of bromine, the reaction mixture was poured on ice (200 g) and the mixture was stirred until the ice melted. The crude product was collected by filtration, twice subjected Christ with so pl. 141-142aboutC.

In this procedure, using diethyl-2-methylpropionyl-2-peridontitis - kilat, got diethyl-5-(2-bromo-2-methylpropionyl)-1,6-dihydro-6-oxo-2,3-Piri - dicarboxylate, so pl. 124-126aboutC.

P R I m e R 27. Getting diethyl-5-(2-bromo-1-oxyethyl)-1,6-dihydro-6-oxo-2,3 - pyridinedicarboxylate and diethyl-2,3-dihydro-3-hydroxy-furo[2,3-b]pyridine-5,6-dick - rboxylic.

< / BR>
Borohydride sodium (2,54 g of 0.066 mol) in parts added for 30 min in stirred suspension of diethyl-5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridine - barcelata (57,2 g, strength of 0.159 mol) at a temperature of 10-20aboutC. When added all borohydride sodium, the reaction mixture was stirred until it reaches room temperature. To the mixture was added to ice (100 g) and stirred it up until the ice melted. The mixture is then concentrated in vacuo, the residue was twice subjected to crystallization from a mixture of ethyl acetate-hexane and received net diethyl-5-(2-bromo-1-oxyethyl)-1,6-dihydro-6-oxo-2,3 - pyridinecarboxylic, so pl. 134-138aboutC. This product was stirred with a solution of triethylamine (1.0 ml/g solids) in methylene chloride for 1 h, then the organic layer was washed with diluted hydrochloric acid, water, brine, obezbedili La was an oil. After crystallization from a mixture of cyclohexane-toluene received net diethyl-2,3-dihydro-3-hydroxy-furo[2,3-b] pyridine-5,6-in primary forms, so pl. 73-77aboutC.

P R I m e R 28. Getting diethyl-2,3-dihydro-3-methoxyfuran[2,3-b] pyridine-5,6-in primary forms.

< / BR>
60% dispersion of sodium hydride in a mixture of mineral oil (2,05 g, 0,0512 mol) and iodomethane (7.9 ml, 0,128 mol) was added to a solution of the ester of the hydroxy acid obtained in example 27 (12.00 g, 0,0427 mol) in tetrahydrofuran (400 ml) under nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then heated at a temperature of 50aboutC in nitrogen atmosphere to remove excess iodomethane. Then the reaction mixture is cooled, filtered, drove and was chromatographically on silica gel. Using as eluent a mixture of hexane-ethyl acetate (4:1), has been the target connection in the form of a yellow oil, yield of 57.3%

Analysis for C14H17NO6< / BR>
Calculated WITH 56,94; N 4,580; N 4,74

Found, 56,93; N 5,59; N A 4.83

P R I m e R 29. Getting diterpene[2,3-b] pyridine-5,6-in primary forms

< / BR>
Solution in xylene of oxyproline obtained in example 23 (3.7 g) containing n-toluensulfonate (0.01 g) was heated at energieteam ether and the extracts combined with xylene. After distillation of the solvents got a solid yellow color, which was subjected to crystallization from a mixture of cyclohexanediol and received net diterpene [2,3-b]pyridine-5,6-in primary forms, so pl. 66-77aboutC.

P R I m e R 30. Getting dimethyl-2-methylfuran[2,3-b]pyridine-5,6-dicarboxylic.

< / BR>
Propyne (3.0 ml, 0.045 mol) skondensiroval in programmirovanie cylinder in a bath with a mixture of dry ice-acetone and added to stirred suspension of dimethyl-1,6-dihydro-5-iodo-6-oxo-2,3-pyridine - carboxylate (13,48 g, 0.04 mol), modestou copper (0,38 g, 0.002 mol) and bis(triphenylphosphine) palladium (II) chloride (2,81 g of 0.004 mol) in 150 ml of DMSO and 50 ml of triethylamine at a temperature of 10aboutC. After the addition propina the reaction mixture was stirred at room temperature for 60 hours Water was added and the mixture was extracted with ethyl acetate. An ethyl acetate solution was washed with water, obezbedili over anhydrous magnesium sulfate, concentrated in vacuum and the obtained mixture of substances. The crude product was isolated using evaporative column chromatography using a mixture of 9:1 methylene chloride in ethyl acetate. The fractions containing specified in the title compound, concentrated in vacuo, the residue was recrystallization of cyclohexane and obrazom substituted acetylene, received the following connections:

< / BR>
< / BR>
CH5147-149

Phenyl 152-153

P R I m e R 31. Getting diethyl-2,3-dihydro-3,3-dimethylurea[2,3-b]pyridine-5,6-in primary forms.

< / BR>
The dibasic ester 5-(2-bromo-2-methylpropyl " keto acid obtained in example 26 (20 g, 0,052 mol), was dissolved in 200 ml of absolute ethanol and the mixture was added 3.0 g of sodium borohydride (0,078 mol) at a temperature of 0aboutC, then the temperature is gradually gave rise to the 15aboutC. the Mixture was stirred for another 1 h, and the ethanol was distilled in vacuum. The hardened mass was treated with water and extracted with methylene chloride. Then the organic extract was washed with water and saturated sodium chloride solution, obezbedili and concentrated. The balance weight 12 g re-dissolved in xylene and the mixture was added 1.0 g of p-toluenesulfonic acid. The solution was heated at the temperature of reflux distilled for 12 h and then cooled. Xylology solution was decanted, the residue washed with several portions of simple diethyl ether. The combined organic solutions were concentrated, then was chromatographically using a mixture of 9:1 methylene chloride ethyl acetate and obtained 3.2 g of oily ester of dibasic acid (21%).

According to the mass-spectrograph M + + 1/e= is barcelata (11,5%).

P R I m e R 32. Getting diethyl-3-bromuro [2,3-b]pyridine-5,6-in primary forms.

< / BR>
Ester of dibasic acid obtained in example 29, (6.0 g, 0,0228 mol) was dissolved in 200 ml of methylene chloride containing 4.6 g of sodium acetate and at a temperature of reflux distilled added bromine (7,3 g, 0,0556 mol). Adding continued, stirring the mixture at the temperature of reflux distilled for 15 min, then the mixture is cooled, washed aqueous sodium bisulfate, obezbedili over sodium sulfate and was filtered. The filtrate was distilled, luciw 8.8 g of crude dibromo connection, which is again dissolved in methylene chloride and treated, and 3.16 g of DBU (0,021 mol) at room temperature for 30 minutes the mixture is Then concentrated in vacuum, was chromatographically on silica gel using a mixture of hexane-ethyl acetate, and had to 7.1 g (90%) dobrosovestnogo ether diethyl-3-bromuro [2,3-b] pyridine-5,6-in primary forms, so pl. is 49.5-52aboutC.

P R I m e R 33. Getting diethyl-2,3-dibromofuran[2,3-b]pyridine-5,6-dicarboxy - lat.

< / BR>
Sodium acetate (2,40 g, 0,0292 mol) and bromine (7.5 ml, 0,146 mol) was added to a solution of diethyl-3-bromuro [2,3-b] pyridine-5,6-in primary forms (5,00 g, 0,0146 mol) in methylene chloride (150 ml). The mixture was stirred at room temperature for creative subjected to back extraction of methylene chloride. The organic solution was combined, obezbedili over sodium sulfate and was filtered. To the filtrate was added 1,8 diazabicyclo [5,4,0] undec-7-ene (4,4 ml, to 0.032 mol) and the mixture was stirred at room temperature for 1 h Then the solution was concentrated in vacuum. The residue was chromatographically on silica gel, poluyanova 20% solution of ethyl acetate in hexane. Received crude 2,3-dibromofuran [2,3-b] pyridine in the form of a solid white color with a yield of 95% and after recrystallization from a mixture of methylene chloride-hexane got diethyl-2,3-dibromofuran [2,3-b] pyridine-5,6-in primary forms, so pl. 96-98aboutWith the release of 75,9%

P R I m e R 34. Getting diethyl-3-cryptomailer[2,3-b]pyridine-5,6-dicarbo - celata.

Na

In the solution trifenatate sodium (0,0234 mol) in N-organic (50 ml) was added 3-bromptonville obtained in example 32 (2,02 g, 0,00585 mol), and copper iodide (2.2 g, 0,0119 mol). The mixture was heated at a temperature of 160aboutC for 3 h in a nitrogen atmosphere, cooled at room temperature, was treated with EtOAc (100 ml) and hexane (100 ml) and was filtered. The filtrate was washed with water (I ml), obezbedili over sodium sulfate, drove to obtain oil, which was chromatographically on silica gel, using as eluent a mixture of GEC m m e R 35. Getting furo[2,3-b]pyridine-5,6-dicarboxylic acid.

< / BR>
A solution of potassium hydroxide (ceiling of 5.60 g, 85% 0,087 mol) in water (5 ml) was added to stir the suspension diterpene [2,3-b]pyridine-5,6-in primary forms (9.3 g, 0.035 mol) in absolute ethanol (100 ml). The reaction mixture was heated at a temperature of 60aboutC for 1 h, then cooled and added anhydrous acetone. The precipitate was filtered, obezbedili, suspended in anhydrous acetone and using hydrogen chloride was moonlighting pH to 2. After crystallization of separated solids from a mixture of ethyl acetate-acetone received furo[2,3-b]pyridine-5,6-dicarboxylic acid, so pl. 189-192aboutC.

P R I m e R 36. Getting anhydride furo[2,3-b]pyridine-5,6-dicarboxylic acid.

< / BR>
Furo[2,3-b] pyridine-5,6-dicarbon - new acid (6.7 g, to 0.032 mol) was heated at a temperature of 60aboutC for 30 min in acetic anhydride (150 ml). The reaction mixture was cooled to room temperature, concentrated in vacuo, the residue is rubbed with a mixture of cyclohexane-simple diethyl ether (5: 1), filtered, obezbedili and got 5.35 g of anhydride furo[2,3-b]pyridine-5,6-dicarboxylic acid.

P R I m e R 37. Obtain 6-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl] furo[2,3 - b]drank in mixed suspension anhydride furo[2,3-b]pyridine-5,6-dicarboxylic acid (3.0 g, to 0.016 mol) in tetrahydrofuran (7.5 ml) and the mixture was allowed to mix at room temperature for 16 hours Then the reaction mixture was stirred at a temperature of 60aboutC for 1 h, cooled to room temperature, added simple diethyl ether, filtered, the solid was obezbedili and received 5 g of 6-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl]furo[2,3-b]pyridine-5,6-carbon th acid, so pl. 192-196aboutC (with decomposition).

P R I m e R 38. Getting 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)fu - ro[2,3-b] pyridine-5-carboxylic acid.

< / BR>
A solution containing a solution of 6-[(1-carbarnoyl-1,2-dimethylpropyl)carbarnoyl] fu - ro[2,3-b] pyridine-5-carboxylic acid (3.8 g, 0.012 mol) in aqueous sodium hydroxide (2.4 g, 0.06 mol) in water (40 ml) was stirred at a temperature of 65aboutC for 3 h Then the reaction mixture was heated at a temperature of 75aboutC for 1 h, gave her the opportunity to cool, poured on ice, acidified to pH 2-3, the obtained solid is filtered and obezbedili. After crystallization from a mixture of acetone-methanol was obtained pure 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) furo[2,3-b]pyridine-5-carboxylic acid, so pl. 237-244aboutC.

P R I m e R 39. Getting 6-(4-isopropyl-4-meat (0.75 g, 0,00391 mol) was added to a suspension of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2 - yl)furo[2,3-b] pyridine-5-carboxylic acid (1.07 g, 0,00355 mol) in sulfolane (63 ml) in nitrogen atmosphere. The temperature of the reaction mixture was maintained in the range 64-85aboutC for three days, during which dissolved solid. The mixture was cooled to 30aboutWith and chromatographically on silica gel. By elution with a mixture of 1:1 hexane-ethyl acetate was removed sulfolan. Then realized elution 1-10% solution of methanol in methylene chloride and recrystallization from a mixture of acetone-hexane, obtained 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-nitrofura[2,3-b]Piri - DIN-5-carboxylic acid, so pl. 220-237aboutC.

P R I m e R 40. Getting 2-isopropyl-2-methyl-5H-furo[2,3-b] imidazo [2',1';5,1]pyrrolo[3,4-e]pyridine-3 (2H), 5-dione.

< / BR>
To a suspension of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo [2,3-b] pyridine-5-carboxylic acid (11.7 g, 0,039 mol) in 100 ml of dimethoxyethane (DME) was added 7.3 ml of acetic anhydride and 3.9 ml of pyridine. The mixture was stirred for 24 h at room temperature, the solids were filtered, washed simple diethyl ether, the mother liquid was concentrated by adding xylene to help remove the pyridine. The mod is received at the first stage, and obtained 11.1 g (100% ) of product. After recrystallization from a mixture of 2:1 ethyl acetate-hexane received a sample with so pl. 193-205aboutC.

P R I m e R 41. Obtaining methyl-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo [2,3-b]pyridine-5-carboxylate.

< / BR>
The compound obtained in example 40 (10,5 g 0,037 mol) is suspended in 150 ml of absolute methanol and the mixture was added 4.0 g of sodium methylate. The mixture was stirred at room temperature for 72 h and then poured on ice, containing acetic acid to maintain a pH of 3-4. Formed a solid white color, it was filtered and got 9,8 g (84%) indicated in the product name with so pl. 134-137aboutC.

P R I m e R 42. Obtaining methyl-3-chloro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazo - Lin-2-yl)furo [2,3-b]pyridine-5-carboxylate.

< / BR>
Methyl ester, described in example 40, dissolved (1.4 g, 4.4 mol) in 20 ml of acetic acid and added sodium acetate (1.0 g, 12.2 mol). After the mixture was passed chlorine gas, the solution was stirred for 2 h and during this time the temperature rose to 40aboutC. the Mixture was cooled, poured into 50 g of ice, extracted with ethyl acetate, washed with distilled water and then a saturated solution of sodium carbonate. The ZAT is sabillo[5.4.0]undec-5-ene (DBU). After 10 min the mixture was treated with 20 ml of cold hydrochloric acid. Methylenchloride layer was removed, obezbedili over anhydrous magnesium sulfate. The mixture is then skipped through the quarter-inch column of silica gel and concentrated in vacuo. After recrystallization from a mixture of hexane-ethyl acetate received 0,85 g (57%) 3-chloromethylene with so pl. 150-156aboutC.

P R I m e R 43. Obtain 3-chloro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2 - yl)furo [2,3-b]pyridine-5-carboxylic acid.

< / BR>
The ester obtained in example 42 (0.55 g, 1,157 mmol) was dissolved in 10 ml of 95% ethanol and added 0.28 g of a 50% aqueous solution of sodium hydroxide. After 1 h the mixture was treated with 10% hydrochloric acid to obtain a pH of 2 and separated product in the form of solid, which was filtered, obezbedili, recrystallization from acetone and obtained 0.35 g (67,3%) of target compound with so pl. 239-240aboutC.

P R I m e R 44. Obtain (+) -6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) furo [2,3-b]pyridine-5-carboxylic acid.

< / BR>
(+)-isomer

Anhydride furo [2,3-b] pyridine-5,6-dicarboxylic acid (2.50 g, of 0.013 mol) is suspended in 40 ml of anhydrous THF and was added to the mixture of (+) -2-amino-2,3-dimethylbutyramide (1,72 g of 0.013 mol). The mixture was stirred in the atmosphere azole obtained solid (crude yield of 88.6%). The crude adduct was converted to the specified in the title compound by the method described in example 38 for the racemic mixture. (+) -isomer has recrystallization of absolute ethanol and insulated from the adduct (yield 27,0%), so pl. 244-245aboutC ( )D2544,5about.

P R I m e R 45. Getting 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)fu - ro [2,3-b]pyridine-5-carboxylate sodium.

< / BR>
NaOH (0,13 g, 0,0033 mol) was dissolved in 50 ml of anhydrous methanol under nitrogen atmosphere. Added free carboxylic acid (1,00 g, 0,0033 mol) and received a yellow solution. The solvent was distilled in vacuum and received a yellow oil. The oil was dissolved in anhydrous ethanol, the solvent was distilled in vacuum and the obtained solid substance. The solid is dissolved in anhydrous ethanol, again besieged simple anhydrous ethyl ether and received specified in the title sodium salt (0,60 g, 56.1 per cent) in a solid yellow color, so pl. 240- >250aboutC.

P R I m e R 46. Getting 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)fu - ro [2,3-b]pyridine-5-carboxylate, compounds with Isopropylamine (1: 1).

< / BR>
Isopropylamine (0.25 ml, 0,00266 mol) was added to a suspension of carboxylic acid (0,80 g, 0,00266 ml) and methanol is haunted particles dissolved. The solvent was distilled in vacuum, the residue suspended in simple diethyl ether, was filtered and got Isopropylamine salt with a yield of 78.1% so 100 to 220 squareaboutWith that slowly decomposes.

P R I m e R 47. Getting imidazolin-2-yl-thieno - and properidine.

As described in the previous examples, the methods using the corresponding thieno - and furo[3,2-b]pyridine or thieno - and furo[2,3-b]pyridine obtained the following compounds:

< / BR>
< / BR>
S H H CH3215-217

S H H H 220-223,5

(decomposition)

S H H-CH2CC 188-189,5

S H H CH 140-142

S H H-CHH2108-110

S CH3H H 225,5-227,5

S H Br H 274-276

S H Cl H 266-267

O H H H 237-244

S H NO2CH3201-202,5

S H NO2H 260 (decomposition)

S Cl Cl H

S H N(CH3)2H

S SC H6H5H

S H SCH3H

S H OCH3H

S H OCHF2H

S CH3CH3H

S H CN H

O H Cl H 239-240

O H H CH3134-137

O H Br H 239-245

O CH3H H 174-177

O C2H5H H 170-172

O C6H5H H 244-245

S Cl H H 268 (decomposition)

O H C CH3137-141

S H CH3H 255-257

S -(CH2)4- H 234-237

O H CF3H

O H SC6H5H

O H H CH 137-141

O H H-CH2B>)2H

S C6H5H H

S -(CH2)3- H

S -(CH)4- H

S H C6H5H

S H OC6H5H

S CF3H H

S C2H5H H

S H C2H5H

S H I H

S H F H

S H CHO H

S H CH2Cl H

S H CF3H

O H NO2H 220-237 (decomposition)

O H N(CH3)2H

O H SCH3H

O H OCH3H

O Cl H H

O Cl Cl H

O H CH3H

O CH3CH3H

O H OCHF2H

O H CN H

O H SO2N(CH3)2H

O -(CH2)4- H

O -(CH2)3- H

O -(CH)4- H

O H C6H5H

O H OC6H5H

O CF3H H

O H C2H5H

O H I H

O H F H

O H CHO H

O H CH2Cl H

In the same way as described for furo[2,3-b]pyridine compounds, obtained 6-(4-isopropyl-4-methyl-5-thioxo-2-imidazolin-2-yl)-thieno [2,3-b] pyridine-5-carboxylic acid with a yield of 37%, and so pl. 242aboutC.

P R I m e R 48. Getting 6-(4-isopropyl-4-methyl-5-thieno-2-imidazolin-2-yl-fu - ro [2,3-b]pyridine-5-carboxylic acid.

< / BR>
Anhydride furo[2,3-b] pyridine-5,6-dicarboxylic acid (1.35 g, 0,0071 mol) is suspended in 25 ml anhydrous THF and added 2-amino-2,3-dimethyl who renderovanie the solid is collected and the filtrate drove to obtain a solid substance. The total yield was 2.30 g (96,2% ). The two portions of solid matter put together in a solution of KOH (1,91 g 0,034 mol) in 20 ml of water. The solution was heated at a temperature of 60aboutC for 4 h, then stirred at room temperature for 16 hours Slightly cloudy solution was filtered, the obtained clear filtrate, which was acidified to pH 4 with 10% HCl. The obtained solid yellow gathered and was heated at the temperature of reflux distilled in 100 ml of xylene for 16 hours Specified in the title compound was obtained by crystallization from a solution of xylene, the yield of 28.0% so pl. 231-232aboutWith decomposition.

P R I m e R 49. Obtain 2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) furo[2,3-b]pyridine-5-carboxylic acid

< / BR>
A solution of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo [2,3-b] pyridine-5,6-carboxylic acid (1.7 g, 0,056 mol) and 1.0 g (0,0072 mol) of potassium carbonate in 200 ml of a 9:1 mixture of ethanol, water was added to 100 mg of 5% palladium on charcoal catalyst in 500 ml thick-walled flask for reactions under pressure. The flask was connected to the apparatus Parr hydrogenation, brought the pressure up to 30 psig with hydrogen and then was shaken at room temperature in tece concentrated in vacuo to a volume of 10 ml. After acidification of the residue until pH 2 was obtained white precipitate, which was removed by filtration, washed with water, dried on air and received 1.0 g (63%) of 2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo - 2-imidazolin-2-yl)furo [2,3-b]pyridine-5-carboxylic acid in the form of solids incorrect white, so pl. 189-192aboutC.

According to the described method a solution of 5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[3,2-b] pyridine (400 mg) can be converted into 2,3-dihydro-5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo [3,2-b]pyridine-6-carboxylic acid, so pl. 205-206aboutC.

P R I m e R 50. Getting 4-mercaptoacetyltriglycine.

CHSH + BrCH2CH2CH2CN __ CH3--S-CH2CH2CN

Toluxury acid (49 ml, 0.69 mol) was added potassium carbonate (for 93.4 g of 0.68 mol) dissolved in water (150 ml). Then added ethanol (260 ml) and 4-bromobutyronitrile at a temperature 15-28aboutC and the reaction mixture was stirred at room temperature for 16 hours Obtained inorganic solid was filtered and the filtrate was extracted with toluene. The organic layer was separated, obezbedili over anhydrous Na2SO4concentrated and got the desired 4-mercaptoacetyltriglycine in the form of oil2-CH2CH2CN

Hydrogen chloride was introduced into a cooled solution of the nitrile in methanol (220 ml) for 1 h and then the mixture was stirred at room temperature for 16 hours the product was filtered, washed simple diethyl ether, dried and got 55,38 g dihydrolipoamide hydrochloride, T. pl. 189-195aboutC.

P R I m e R 52. Getting dimethyl[(tetrahydro-2-dienylidene)amino]fumarata (and maleate).

+< / BR>
< / BR>
Diethylazodicarboxylate (0.45 ml, 0,037 mol) was added to stir the solution dihydrolipoamide hydrochloride (0.5 g, 0,0036 mol) in methanol (60 ml) containing sodium acetate (0.3 g, 0,0036 mol) in nitrogen atmosphere at a temperature of -15aboutC. the Solution was stirred for 16 h at room temperature, then in a rotary evaporator removed the solvent, and the resulting mixture was separated using column chromatography on silica gel, using as eluent a mixture of methylene chloride-acetonitrile (19:1), was obtained 0.68 g (78% yield) of the desired mixture of isomers, esters of acids in the form of a yellow oil.

P R I m e R 53. Getting dimethyl-2,3-dihydrothieno[2,3-b]pyridine-5,6-dicarbo - xylota

< / BR>
The reagent Vilsmeier prepared by adding oxalicacid (0, in an inert atmosphere of nitrogen. The solution in 1,2-dichloroethane (50 ml) dimethyl[(-tetrahydro-2-dienylidene)amino]femara (and maleate) (0,0028 mol) was added to the reagent Vilsmeier, and the reaction mixture was heated at the temperature of reflux distilled for 4 hours, the Reaction mixture was extinguished with water, parselocale with sodium bicarbonate, the organic layer was separated and obezbedili over anhydrous sodium sulfate. The solvent was distilled in vacuum and the residue was chromatographically on silica gel, using as eluent a mixture of methylene chloride-acetonitrile (19: 1). After crystallization from a mixture of toluene-hexane got dimethyl-2,3-dihydrothieno [2,3-b]pyridine-5,6-in primary forms in a solid white color with so pl. 102-103aboutC.

P R I m e R 54. Obtain 2,3-dihydro-6-(5-isopropyl-5-methyl-4-oxo-2-imidazo - Lin-2-yl) thieno[2,3-b]pyridine-5-carboxylic acid 1-oxide.

< / BR>
< / BR>
Meta-chlormadinone acid (2.0 g, 0,0094 mol) was added to a solution of dihydrotriazine in a mixture of methylene chloride (400 ml) and methanol (40 ml) at a temperature of 0aboutC in nitrogen atmosphere. The solution was stirred for 16 h, maintaining the temperature of the 18aboutWith added 100 ml of water and 100 ml of a saturated solution of NaHCO3. The aqueous layer was separated and washed with methylene chloride. The mixture was acidified to the layer have expended to 1. After extraction of this acidified layer of methylene chloride and removal of the solvent has been specified in the title product as a white solid with so pl. 216-218aboutWith decomposition.

P R I m e R 55. Getting diethyldichlorosilane [3,2-b]pyridine-5,6-in primary forms.

< / BR>
In the solution of tetrahydrothiophene-3-one Maybridge Chem. With; 20,0 g, 0,196 mol) in benzene (100 ml), stir at room temperature was added piperidine (16.7 g, 0,196 mol) and p-toluenesulfonic acid monohydrate (0.20 g, 0.001 mol). The mixture was heated at the temperature of reflux distilled to trap Dean-stark for 4 h, cooled and drove away, having a dark brown oil, which is a mixture 1:1 of 2,3 - and 2,5-dihydrolipoamide (I and II, Recl. Trav. Chim. , 865 (1973)). In this mixture of enamines added ethanol (100 ml) and diethylethylenediamine (72,1 g, 0,294 mol) and the mixture was stirred for 45 minutes In a mixture in one portion was added ammonium acetate (45,3 g, 0,588 mol) and heated it at the temperature of reflux distilled within 45 minutes the Mixture was cooled, the solvent was distilled and after chromatography (eluent hexane-ethyl acetate) received diethyldichlorosilane [3,2-b]pyridine-5,6-in primary forms. Mass-spectrogram has the maximum peak (m+1/e) at 282.

the one-5,6-in primary forms.

< / BR>
In a solution of tetrahydrofuran-3-one (J. Pharm. Sci. 59, 1678 (1970); 46,55 g, 0,540 mol) in benzene (250 ml), stir at room temperature was added piperidine (45,98 g, 0,540 mol) and p-toluenesulfonic acid monohydrate (0,46 g, 0.002 mol). The mixture was heated at the temperature of reflux distilled to trap Dean-stark for 4 h, cooled, drove to obtain a dark brown oil, which is a mixture 1:1 of 2,3 - and 2,5-dihydrolipoamide. Then to the mixture was added ethanol (500 ml) and diethylethylenediamine (178,79 g, 1.35 mol) and continued to stir for 45 minutes Then added ammonium acetate (124,87 g of 1.62 mol) and the mixture was heated at the temperature of reflux distilled within 45 minutes the Mixture was cooled, the solvent was distilled and the yellow oily diethyldithio[3,2-b]pyridine-5,6-carboxylate was subjected to purification using chromatography on silica gel, using as eluent hexanitrate. Mass-spectrogram maximum peak (m+1/2) there is at 266.

P R I m e R 57. Obtain 2,3-dihydro-5 and 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo - and thieno[2,3-b] and [3,2-b]pyridines.

According to the methods described in the examples 8,10,12,15,18,27,35,36,37,38,49,53,54,55 and 56, received the following dihydrocodiene:

< / BR>
' '3< / BR>
>O H H 140-143

< / BR>
' '

S H H H H H 239-241

O H H H H H 205-206

< / BR>
< / BR>
S H H H 242-244

S H Cl H 238-239

S H Br H 226-227 of the

S H H CH 156-157

O H H H 214-223

S Cl H H 266-267

O H Cl H

O H CH3H

O CH3H H

O C2H5H H

O H C2H5H

O CH3CH3H

S H CN H

S H CH3H

S CH3H H

S CH3CH3H

S H NO2H

S H N(CH3)2H

S H SCH3H

S H OCH3H

S H OCHF2H

S Cl Cl H

S H SO2N(CH3)2H

S C6H5H H

S H C6H5H

S -(CH2)3- H

S -(CH2)4H

S -(CH)4- H

S H OC6H5H

S CF3H H

S C2H5H H

S H C2H5H

S H I H

S H F H

S H CHO H

S H CH2Cl H

S H CF3H

S SC H6H5H

P R I m e R 58. Evaluation of herbicide activity of the test compounds in post-harvest processing.

Post-harvest herbicide activity proposed compounds shown by the following tests in which a number of monocotyledonous and dicotyledonous plants are treated with test compounds, dispergirovannykh in water acetonaemia connection was dispersively in a mixture of 50:50 acetone-water, containing 0.5% TWEEN 20, polyoxyethylenesorbitan, SAS, Atlas Chemical inductries in sufficient quantities in order to get the equivalent dose of 0.16-10 kg/hectare of active compound when spraying plants through a spray nozzle operating at a pressure of 40 pounds per square inch for a certain period of time. After spraying, the plants were placed in a greenhouse and cared for them in the usual way. After 4-5 weeks after treatment, the seedling plants are examined and rated according to the following system. The data obtained are given in table.1.

The system of assessing differences in growth from the control-

Noah group

0 no effect 0

1 possible effect 1-10

2 weak effect 11-25

3 average effect 26-40

4 abnormal growth that

means certain Phi

zoologichesky nadrazi-

lead, but the overall effect is weaker,

than 5

5 some damage 41-60

6 herbicide effect 61-75

7 good herbicide effect 76-90

8 is bordered complete destruction 91-99

9 the complete destruction of 100

In most cases, data are given for one test, but in some cases they represent an average value according to more than one test.

Pre-emergence herbicide activity proposed compounds represented by the following tests in which the seeds of various one - and dicotyledonous plants are separately mixed with soil humus pots and planted to a depth of 1 inch in separate pots. After planting, the pots were sprayed with the selected aqueous-acetone solution containing test compound in sufficient quantity to obtain the equivalent dose 0,016-10 kg/ha of test compound per pot. The treated pots were placed in the greenhouse, watered and cared for them as usual. After 4-5 weeks after treatment, each pot was examined and evaluated according to the system above. Herbicide active active ingredientis more than one test, the average data.

The primary name Common name Scientific name

Bornyarolgr Chicken millet Echinochloa orus-galli (L) Bear

Bermudagrs Bermuda grass Cynodon Dactylon (L) Pers

Lorhe rab Weed blood Digitaria Sougninalis (L) Scop

Foxtail Alopecurus sp Setaria spp spp

Giant Fox Alopecurus giant Setaria Faberi, HERR4

Green Fox Alopecurus green Setaria viridis (L) Brady

Yellow Fox Alopecurus yellow Setaria Lutescens (Weige/HUBB)

Johngrs Pr Jonssonova grass s Orghum Balepense (Prizames)

(Rhizome)

Millet Pros Millet cultural Panicum Miliacum, L

P. Nutsedgl Sedge purple Cyperus Protundus, L.

Y. Nutsedgl the yellow Sedge Cyperus Esculantus, L.

Wild Oatd wild Oats Avena Fatua, L.

Anackgrass Elytrigia repens Agrapyron Repens (L). Beary

Fed BINDWD the Bindweed Convelsulus arvensis, L.

Nts Had Red Nightshade red Solanum Dulcamara

Scale evaluations of herbicide

The results of the study herbicide expressed in the rating scale (0 to 9). The scale is based on the visual observation of the grass, power plants, wrong formation, size, chlorosis and the General appearance of the plants compared to control plants.

The rating scale Is suppression in comparison with the control

plant

9 the Complete destruction of 100

8 approximation to the full 91-99

destruction

7 Good is possible

4 Damage 30-44

3 Moderate action 16-29

2 Weak action 6-15

1 Traces of steps 1-5

0 No action 0

1. Derivatives (2-imidazolin-2-yl) thieno or furo(3,2-C)pyridine carboxylic acid of the formula I

< / BR>
< / BR>
where denotes a single or double bond;

R1and R2WITH1WITH4-alkyl;

AND CO2R3where R3hydrogen, C1WITH4-alkyl, methylphenyl,3WITH4-alkyl, C3WITH4-quinil,

< / BR>
In hydrogen;

W is oxygen;

X is oxygen, sulfur or >S 0;

Y is hydrogen, C1WITH4-alkyl, halogen, phenyl;

Y is hydrogen;

Z is hydrogen, C1WITH4-alkyl, hydroxy, nitro-group, WITH1- C4-alkoxy;

Z is hydrogen, methyl,

or Y and Z may together form a ring including the chain -(CH2)4- and when R1and R2unequal, their optical isomers, except for the case when R3is a salt-forming cation, showing herbicide action.

2. Herbicide composition comprising an arbitrary imidazolin-2-yl carboxylic acid and the target additives, characterized in that as a derivative (imidazolin-2-yl)carboxylic acid ISPO. Compounds of General formula II

< / BR>
< / BR>
where a single or double bond;

R1and R2WITH1WITH4-alkyl;

X is oxygen, sulfur or >S 0;

Y is hydrogen, C1WITH4-alkyl, halogen, phenyl;

Y is hydrogen;

Z is hydrogen, C1WITH4-alkyl, hydroxy, nitro-group, WITH1- C4-alkoxy;

Z is hydrogen, methyl;

or Y and Z may together form a ring including the chain -(CH2)4- and when R1and R2unequal, their optical isomers,

and acid additive salts as intermediates for producing compounds of General formula I(a) and (b).

4. Compounds of General formula III

< / BR>
< / BR>
where R3hydrogen, C1WITH4-alkyl, methylphenyl,3- C4-alkyl, C3WITH4-quinil,

W is oxygen;

a single or double bond;

R1and R2WITH1WITH4-alkyl;

X is oxygen, sulfur or >S 0;

Y is hydrogen, C1WITH4-alkyl, halogen, phenyl;

Y is hydrogen;

Z is hydrogen, C1WITH4-alkyl, hydroxy, nitro-group, WITH1- C4-alkoxy;

Z is hydrogen, methyl,

or Y and Z may together form a ring including the chain -(CH2)4- and to the mediate connections to obtain compounds of General formula II(C) and (d) under item 3.

5. Compounds of General formula IV

< / BR>
< / BR>
where R is methyl or ethyl;

X is oxygen, sulfur or >S 0;

Y is hydrogen, C1WITH4-alkyl, halogen, phenyl;

Y is hydrogen;

Z is hydrogen, C1WITH4-alkyl, hydroxy, nitro-group;

WITH1WITH4-alkoxy;

Z is hydrogen, methyl,

or Y and Z may together form a ring including the chain -(CH2)4and their optical isomers,

and acid additive salts as intermediates for producing compounds of General formula III(e) and (f) under item 4.

 

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CFN< / BR>
where R represents a hydrogen atom or methyl;

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< / BR>
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