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    • 专利摘要:
    Compounds are described of the formula <IMAGE> in which R1 is COOR5, CONHR5, cyano, 5-tetrazolyl or 5-tetrazolylaminocarbonyl, where R5 is hydrogen or C1-6 alkyl; R2 is hydrogen or C1-6 alkyl; R3 is a group of the formula R6-(Z)m- where m is O or 1, Z is O, S, SO, SO2 or CO, and R6 phenyl optionally substituted by one or more group selected from halogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, benzyloxy, hydroxy, nitro, C1-4 alkylthio, C1-4 alkylsulphinyl, C1-4 alkylsulphonyl, amino and NHR7 where R7 is C2-6 acyl; and R4 is hydrogen, C1-6 alkyl or halogen; and salts thereof. These compounds have pharmaceutical properties and in particular are useful in the treatment of immediate hypersensitivity conditions such as asthma.
    公开号:SU976850A3
    申请号:SU802905747
    申请日:1980-04-04
    公开日:1982-11-23
    发明作者:Питер Кларк Барри；Джеймс Росс Вильям；Тодд Алек
    申请人:Лилли Индастриз Лимитед (Фирма)；
    IPC主号:
    专利说明:

    where fl has the indicated values, in the presence of a base and the resulting compound of total yormula Y.CH where R2, R3, Rff have the indicated meanings, is cyclized in the presence of acid and the desired product of formula (1) is isolated, where R is a COOR radical pas, p of which R is a hydrogen atom or C-C-alkyl, and / or translates it into a c. compound of formula (D), where R is a cyto group, 5-tetrazolyl or -COUHR group, or the target a product of the general formula (1), where R is Phenyl, mono- or disubstituted with a CjC alkoxy group, and / or is translated, it into a compound of the total (Formulas (1), where R is pheny l, mono- or disubstituted with the hydroxy group, and the desired product is isolated and / or translated into a compound of the general formula (O, where R is Phenyl, mono- or disubstituted by the benzyl cosigroup. Pyranones (1) and their Pharmaceutically acceptable salts are useful in the prophylactic and therapeutic treatment of urgent hypertensive diseases, including asthma, and in alleviating the status asthmatlcus. They are also of low toxicity. This activity is shown in guinea pigs using any of the intermittent respiratory strains in guinea pigs described by Mongar and Shildo or Guklehmurs, or with the help of the Herxheimer test. For example, compounds of Formula O), which show more than 15 mediators inhibition, have a facilitating effect in intermittent breathing test in guinea pigs. In the case of the Gerksgey Mer test, which is based on allergic Pronhospasm induced in guinea pigs, very similar to an asthma attack in humans, compound (1) exhibits an activity with a dosage ranging from 25 to 200 mg / Compound of the formula ( 1) can be administered in various ways, although the 97 04 reading feature of the compound of the formula (t) is that they are effective for oral administration. Therefore, these compounds can be administered orally and rectally, topically and parenterally, for example, by injection, in commonly used forms of pharmaceutical compositions. Such compositions are prepared according to the methods xopoDo known in pharmacy, and usually they include at least one active compound or salt. When prepared, compositions of the active ingredient are usually mixed with a carrier or diluted by a carrier, or enclosed inside a carrier, which may be in the form of a capsule, pouch, paper or other container. When the carrier serves as a diluent, it may be solid, semi-solid or liquid. a material that acts as a drug carrier, excipient or medium for the active ingredient. Consequently, the composition can be in the form of tablets, pellets, pouches, wafers, elixirs, suspensions, aerosols (in the form of solid or liquid food), ointments containing, for example, up to TO wt., active compound, soft or hard chelating capsules, suppositories, suspensions for injections and sterile packs of powders. Examples of some suitable notes are lacto, dextrose, sucrose, sorbitol , mannitol, starches, gum, calcium phosphate, alginates, tragacanth, gelatin, syrup, methylcellulose, methyl- and propyloxybenzoate, talc, magnesium stearate or mineral oil. These compositions can be formulated to provide rapid, prolonged or delayed treatment of the active ingredient after administration to the patient. Preferably, the compositions are formulated in unit dosage forms, each dose containing from 5 to 500 mg, typically from 25 to -00 mg, of the active ingredient. The term unit dosage form refers to Physically discrete units suitable for single dosages in humans and animals. Each unit contains a predetermined amount of active material calculated to obtain the desired therapeutic effect, along with the required Pharmaceutical carrier. The active compounds are effective}) effective over a wide dosage range.
    WITH (-C1
    12:
    it-CHjO
    126.
    with
    Example 16. -Dimethylamino-3 (| methoxyphenyl) -3-buten-2-one.
    Example 27. “-Lethylamino-3-yenyl-3-buten-2-one.
    Reflux boil over 1.75 g of diethylstyrylamine in 5 ml of acetic anhydride for
    hour, and then distilled in vacuum (0.0. mm) in a vessel vessel (above (; 150 ° D,). The product is recrystallized from ether-petroleum ether (() at low temperature, J getting crystals of the desired product, which melts at about room temperature.
    This compound is reacted with diethyloxalate in accordance with the procedure described in Example 17, to obtain a product, ethyl eLir-oxo-B-phenyl-W-pyran-2-carboxylic acid, identical to the product of Example 17.
    Example 28. it-OKCo-5-phenyl-15 -4H-pyran-2-carboxylic acid.
    Heat, E f ethyl ester of -oxo-5-Lenyl-And-pyran-2-carboxylic acid with 12 ml of concentrated hydrochloric acid on the steam bath for 20 hours and a half hours. The mixture is cooled and the solid target product is recrystallized from a mixture of ethyl acetate - dimethylmormaide (mp. With decomposition) .23
    Example 29. 5 (-ChlorLenylthio) - -ox-ll-pyran-2-carboxylic acid.
    A solution of 5.0 g of ethyl 30-chlorophenylthio) - -oxo-H-pyrene-carboxylic acid in 00 ml of dioxane and 20 ml of concentrated hydrochloric acid is boiled under reflux for 2 hours, then evaporated in vacuo . The solid residue is dried and nepeis is crystallized from ether-petroleum ether (BO-C C) to obtain the desired product (m.p. 1: 5-1: 7 ° C with decomposition).
    Example 30. 5 - (- Methylphenylsul ()) - -oxo-4H-pyran-2-carboxylic acid.
    This compound is obtained according to the procedure described in Example 29 (mp. 210 ° C with decomposition) .45
    Example 31. 5- (-MethoxyPhenyl) -oxo-W-pyran-2-carboxylic acid.
    An ethyl esir of 5- (-methoxyphenyl) -A-oxo-H-pyran-2-carboxylic acid (mp. 121-123 ° C) is obtained from the procedure of Example 17 and hydrolyzed according to the procedure described in Example 29, to give target product (mp. 23223 ° C with decomposition).
    Example 32. 5- (2-Netoxy (benoxy) - | -oxo-H-pyran-2-carboxy acid.
    Ethyl eLir 5 (2-methoxyphenoxy) -4-oxo-4H-pyran-2-carboxylic acid (mp. C) is prepared according to the procedure of Example 17 and hydrolyzed according to the procedure of Example 29 to obtain the acid target product (mp. 202-203 ° C).
    Example 33. -Oxo-5-phenylthio-4H-pyran-2-carboxylic acid.
    Α-Oxo-5-phenylthio-N-pyran-2-carboxylic acid ethyl ester (mp. 79-81 ° C) was prepared according to the procedure of Example 17 and hydrolyzed according to the procedure of Example 29 to obtain the desired product (mp. 178 -181 ° C).
    Example 3t. Propyl ester of 5- (4-methoxyphenylthio) - -oxo-H-pyran-carboxylic acid.
    3-C-methoxophenylthio) -4-oxo-AN-pyran-2-carboxylic acid ethyl ester is obtained (mp. 90-92C) according to the procedure described in Example 17, and it is hydrolyzed to acid (mp 190 -193 C) according to the procedure described in Example 29. A solution of 5, g of this acid in 50 ml of carbon tetrachloride, 2.9 ml of propanol and 2.7 ml of triethylamine is heated under reflux for 7 hours, dried, washed diluted hydrochloric acid, then sodium carbonate solution, dried and evaporated. The residue is crystallized from ethyl acetate-petroleum ether (6080 ° C), to give the desired product (e.g. 91-93 ° C).
    Example 35 N-Methyl-oxo5-phenyl-H-pyran-2-carboxamide.
    A suspension of 4,3, -oxo-5 Fvnil-H-pyran-2-kgrboxylic acid in 50 ml of dry benzene and 10 ml of thionyl chloride is boiled under reflux with stirring for 12 hours. The clear solution is diluted with petroleum ether (60- 8 ° C), 50, and cooled, obtaining crystals of xLoranhydride - v (mp. 175 ° C). A solution of methylamine (0.388 g) in dry pyridine (4.5 ml) is added to a stirred, cooled suspension of 2.5 g of acid chloride in 15 MP of dry pyridine. The solution is stirred at room temperature for one hour, then cooled and diluted with 50 ml of water. The solid target product is dried and recrystallized from a mixture of chloroform - petroleum ether (60-80 0), so pl. 19b-198
    il p and measures 3 (-37. The compounds listed in Table 3 are prepared according to the procedure described in Example 35. CONHKj a j Example Example 38.4-Oxo-5-phenyl-H- ( 5; -tetrazolyl) -H-pyran-2-carboxamide. A suspension of 0.9 g of hydropy 5 amine tetrazole in 50 gl benzene is heated in a Dean and Stark trap with stirring until water is distilled off. The mixture is cooled and diluted, and the solid product is immediately dissolved in dry pyridine (20 ml). Add 2.0 g of solid 4-oxo-5-lenyl- | C-pyran-2-carboxylic acid chloride (prepared according to the method of example 35) to cooled P Read the new solution with stirring. The mixture is stirred for 2 hours at room temperature, cooled and diluted with 50 ml of water. The solid desired product is recrystallized from dimethylformamide (mp 300 ° C). Example 39. P-Butyl-ioxo-5-phenoxy - N-pyran-2-carboxamide Hydrolyzing to acid (204-20b ° C with decomposition) ethyl ester of 4-oxo-5-phenoxy-H-pyran-2-karponovoy - acid according to the method of example 29. Boil with reverse the suspension with suspension of 3.6 g of this acid in 0 ml of dry benzene and 7.7 ml of thionyl chloride for 12 hours while stirring. minutes the solution was evaporated in vacuo. The remaining oil is dissolved twice in dry benzene and re-evaporated to give crude acid chloride, which is reacted with 1.5 ml of butylamine in dry pyridine according to the procedure of example 35. Target product is the desired product (mp. 1 9-151 C) Example (P. —C — methoxyenyl) -4-oxo-J-pyran-2-carboxamide. Add a cold concentrated solution () of 80 ml of ammonia 1C of a stirred suspension of 12, 5 - (- methoxyo-nyl) - -oxo-H-pyran-2-carboxylic acid ethyl ester in 120 ml of ethanol at. The mixture is 0-5 ° C, stirred for another 30 minutes, then the solid desired product is washed with water and dried (mp 2-2-2 ° C, decomposed). N f) and meper 1. bc-Netoxyphenyl) - -oxo-H-pyran-2-car-nitrile. A suspension of 8.0 g of B-C-methoxyphenyl) - + - oxo-H-pyran-2-carboxamide and 17.1 g of triphenylphosphine in 80 ml of carbon tetrachloride, 1 BO of methylene chloride and 55 ml of triethylamine are stirred for 3.5 hours at room temperature. Add 2 and. 100 ml hydrochloric acid solution to the stirred mixture while cooling, then the solvent layer is washed with water, dried and evaporated. The solid residue is crystallized from a mixture of chloroform - petroleum ether (BO-YAO C) to obtain the desired product (i.p. 1b51 ° 7 (;). Example 2.-Oxo-5-phenyl-4H-pyran-2-carbonitrile. Add Q ml of concentrated ammonia solution to a stirred suspension, 8 g of ethyl ester. -Oxo-5-phenyl-4H-pyran-2-carboxylic acid in tO ml of ethanol at 10-15 C. The mixture is then stirred for another 30 minutes at 10-15 ° C Then the solid product is recrystallized from a mixture of dimethylformamide - ethanol, get 4-oxo-5-phenyl- (H-pyran-2-carboxamide (so pl. 2 t5-2f | 8 ° C with decomposition). Suspension 3.5 g this o amide and 8.5 g of triphenylphosphine in 10 ml of carbon tetrachloride, 20 fin methylene chloride, 2.3 ml of triethylamine are stirred at room temperature. 60 g of ice and 30 ml of 2N hydrochloric acid are added, followed by the addition of chloroform to dissolve of the solid material. The solvent layer is washed with water, dried and evaporated, and the residue is crystallized from chloroform-petroleum ether (B-PO C), and then from ethanol, the desired product is obtained (mp. 177179С). Remark 5-Oenyl-2-tetrazolyl-nH-pyran- | -one. A mixture of 2.0 g of A-oxo-5-functional-H-pyran-2-carbonitrile, 1.0 g of sodium azide and 0.8 g of ammonium chloride and 20 ml of dimethylformamide is stirred at room temperature for an hour. 20 g of ice are added, and a clear solution of 20 ml 2 N is added. solid acid to obtain the desired solid
    a substance that is recrystallized and;) ethanol gives the desired product (mp. 237-23fiC with decomposition).
    Example k, 5 ((Methoxyphenyl) -.-tetrazol-5 yl-H-pyran---one.
    This compound is prepared according to the procedure described in Example O. (mp. 242-245 ° decomposition) .;
    fl p i me R 5. Ethyl esyr 5 (Oxyenyl) - (- oxo-M-pyran-2-carboxylic acid.
    3 ml of 5- (2-methoxyenyl) -xoxyn-pyran-2-carboxylic acid ethyl ester in 100 ml of methylene chloride are added dropwise to a stirred rator of boron tribromide 3, added dropwise. The mixture is stirred for 2 hours at room temperature, the mixture is cooled to and thoroughly washed with 50 ml of water. The solid target product is recrystallized from ethanol (mp. 187-189 ° C). -.
    PRI me R 6. Ethyl ester of 5- (4-hydroxyphenoxy) -t-oxo-H-pyran 2-carboxylic acid.
    5 - (- methoxpheno1Csi) -4-oxo-L-pyran-2-carboxylic acid ethyl ester is obtained according to the method of Example 17 and the methoxy group is cleaved according to the procedure described in Example 5 to obtain the desired product (mp. 206-208 ° C ) PRI me R 7. Ethyl Air 5 - (- hydroxyoenoxy) - oxo- (1 pyran-2 carboxylic acid.
    This compound is prepared according to a procedure similar to that described in the example) (mp. III-IIB C).
    Example tO. 5 (Oxyphenoxy) - -oxo-H-pyran-2-carboxylic acid.
    8.8 ml of boron tribromide are added dropwise to a stirred solution, 35 g of ethyl air of 5- (-methoxyphenoxy) -oxo-4H-pyran-2-carboxylic acid in 50 liters of methylene chloride with careful boiling under reflux. The solution is heated under reflux for another 2 hours, then cooled and carefully diluted with 25 ml of water. The solid product is recrystallized from water (mp. 257-258 ° C with decomposition).
    Example f9. 5- (2-Oxyphenoxy) - | -oxo- | 1-pyran-2-carbono8a acid.
    This compound is prepared according to the procedure described in Example 8 (mp. 193 with decomposition).
    Example 50. 5- (| -Methoxybenzoyl) - -oxo-4H-pyran -, - carboxylic acid ..
    0 () treatment of ethyl air 5 (1methoxybenzoyl) - -oxo-H-pyran-2carboxylic acid with boron borobromide under the conditions described in example 45 causes cleavage of the ester group, get the desired product (so pl. 185-190 With decomposition).
    Example 51. C (3, -Dimethoxyphenyl) -dimethylamino3 buten-2-one.
    This compound is prepared according to the procedure described in Example 1 (mp. 9t ° C
    Example 52. 5- (3, -dimethoxyphenyl) - (- oxo-H-pyran-2-carboxylic acid ethyl ester.
    This compound is prepared according to the procedure described in Example 17 (mp. (.}.
    Example 53. 5- (3, Dimethoxyphenyl) -t-occo-tH-pyran-2-carboxylic acid
    This compound is prepared according to the procedure described in Example 29 (mp. 2101212 ° D, with decomposition).
    Example 5 |. Ethyl ester of 5 - (3, -dioxylenyl) - -oxy-H-pyran-2-carboxylic acid.
    This compound is prepared according to the procedure described in Example 5 (mp. 206208 ° (;).
    Example 53. 5 (3, Dioxyphenyl) -oxo-H-pyran-2-carboxylic acid.
    This compound is prepared according to the procedure described in Example 29 (mp. 284285 ° C., decomposition).
    Pr meper 5b. 5- (3, Dimethoxy-phenyl) -N-methyl-oxy-4H-pyran-2-carboxamide.
    The acid chloride 5 (3 dimethyloxyOlenyl) -4-oxo-AP-pyran-2-carbono acid of your acid (m.p.) is taken and reacted with methylamine according to the procedure described in example 33 to obtain the desired product (m.p. 213- -15 ° C).
    Example 57. 3- (31 -Dibenzyl-yxenyl) - -oxo-4I-pyran-2-carboxylic acid.
    Mix the mixture of g of ethyl ether 3 (3, -dioxy (nickel) - -Oxo-iH-pyran-2-carboxylic acid, 6.0 g of anhydrous potassium carbonate and ml of benzyl bromide in 30 ml of dry dimethylformamide at room temperature for 2 and then filtered. The filtrate is cooled, acidified with 20 ml of 2N hydrochloric acid and diluted with 80 ml of water. The solid product is recrystallized from ethanol to give ethyl eLir 5 (3, Dibenzyloxyphenyl) -t-oxo-4M-pyrane -.- carboxylic acid (so pl. 122-125 ° C). A solution of 7.5 g of ethyl ether, obtained by heating, is heated on an oil bath at TbZ-IO C with stirring and lij g of lithium iodide in 12P ml of dry dimethyl Lormamide in atmosphere / nitrogen for 6 hours. The solution is cooled and acidified with 500 ml of 1N hydrochloric acid, the recrystallized solid from ethanol to give the desired product (t 206-208 C). Example 58. 5- (4-tert-Butylbenzoyl) -it-OKCo-tHpyran-2-carboxylic acid ethyl ester. Get 3 (t-tert-Butylbenzoyl) -dimethylamino-3-butene-2 -one according to the procedure described in Example 16 and used without purification to obtain the target compound {m.p. 8285 C) according to the method of Example 17. Example 59. 5 - (- tert-Butylbenzoyl) - oxo-1H-pyran-2-carboxylic acid. This compound is obtained by cleaving ethyl ether as described in Example 0 (mp. 133-1 ° C). EXAMPLE 60 3 - (- tert-Butylfeioxy) - -dimethylamino-3 butene-2-one This compound is prepared according to the method described in Example 1 (mp.98 ° Example 61. 5- ( 1-tert-butylphenoxy) -A-oxo- | H-pyran-2-carboxylic acid. 5- (T-butylphenoxy) -oxo-1H-pyran-2-carboxylic acid ethyl ester is obtained (T.nnv 108-110 ° С ) according to the procedure described in Example 17 and hydrolyzed as described in Example 2 to obtain the desired product (mp. 190193, with decomposition). Example 62. (Cyclohek%, OS forces) -phenoxy J-h-dimethylamino- 3-Outene -2-one. Add 31 fv of freshly distilled chloroacetone to a solution of 1.0 g of sodium iodide. 50 ml of dry acetone. The mixture is left to stand for one hour at room temperature and then added to the boiling mixture of 52.8 g (cyclo xylo) phenyl and 52 g anhydrous potassium carbonate in 100 ml of dry acetone. The mixture is boiled under reflux while stirring for another 5 hours, filtered and evaporated to a brown oil, which is crystallized from ether-petroleum eLir), obtained from 1-hexyl) -6 penoxy 2-propanone (m.p. ). The desired product is obtained from this ketone according to the procedure described in Example 1 (mp). Example 63. (11-cyclohexyl) -phenoxy-3-oxo | And-pyran-2-carboxylic acid. The ethyl ester of (cyclohexyl) phenoxy-l-oxo-H-pyran-2-carboxylic acid (m.p.) is obtained according to the procedure described in example 17 and hydrolyzed as described in example 29 to give the desired product (m.p. 187-190 ° C). Example 6 of 5- (-Butylphenyl) -oxo-H-pyran-2-carboxylic acid. A solution of 13.5 g of 4-butylbenzaldehyde, ml of nitroethane and 1.6 ml of butylainin in 20 ml of ethanol is boiled under reflux with stirring for 6 hours and evaporated. The residue is distilled in vacuo to yield 1- (-butylphenyl) -2-nitropropene (b.p. 124-12.5 ° C / 0.15 mm). 6.5 ml of concentrated hydrochloric acid are added in small portions over a period of 6 hours to a peremimisable mixture of 7.6 g of this nitropropene, 13.6 g of iron powder and 0.1 g of ferric chloride in 50 v of water at reflux. . The mixture is distilled with steam and the distillate is extracted with ether. The cyiuFT extract was evaporated and the residue was distilled in vacuo to give 1- (h-butylOnyl) -2-propanoHg. The reaction ", 6 g of this ketone with dimethylformamide dimethyl acetal (+, 0 ml), as described in Example 1, was obtained. 3- ("butylphenyl) -4-dimethylamino-3 buten-2-one that is used,. o® of purification to obtain ethyl ester of 5 (butyL1enyl) - -oxo- | H-pyran-2-carboxylic acid (m.p. b5C) according to the procedure described in Example 17. This ester is hydrolyzed according to the procedure described in Example 29, to obtain the desired product (mp. 193-195 ° C). Example 65. 3-bromo-oxo-5-phenyl-H-pyran-2-carboxylic acid ethyl ester. A suspension of sodium ethoxide is prepared by adding ethanol (1.6 ml) and a stirred suspension of 1.3 g of sodium hydride dispersion washed with petroleum ether 40-60 ° C in 50 ml of ether under a nitrogen atmosphere. The solution, 8 g of 4-dimethyl amino-3 phenyl-3 5-uten-2-one and 5.2 ml of diethyl oxalate in 50 ml of ether are added with stirring to a suspension of sodium ethoxide at, and the resulting transparent pacnnop is obtained. stirred for another 2 h at room temperature, then cooled and treated with glacial acetic acid (2.5 ml) and 50 t-ui of water. Ethyl acetate was added to dissolve the solid that had formed and the layer was re-crystallized from ethyl acetate-petroleum ether (60-8P ° C) to give 6-dimethylamino-2, dioxo-5-phenyl-5-hexanoic acid ethyl ester (mp. 110 ° WITH). A solution of 0.73 ml of bromine in 10 ml of chloroform is added dropwise to a stirred solution of this hexanate (1 g) in 50 ml of chloroform at up to. The solution is stirred for 1.5 hours at room temperature, washed with water and evaporated. The remaining solid product is crystallized from ethanol-water to give the desired product (mp. -). The following examples illustrate pharmaceutical formulations containing compounds (Formula (1). The active ingredient used is 4-oxo-5 Feiyl- | H-pi9 016 ethyl ester), the granules are dried at about 55 ° D, and passed through a No. 16 sieve. Magnesium stearate and sodium starch glycolate, passed through a No. 60 mesh U sieve. Add granules which, after mixing, are compressed into a tablet machine to obtain tablets each weighing 500 mg. Example 67. Ready t capsules containing 50 mg of the drug, next va, mg: Active ingredient 50 Starch .42 Lactose. Magnesium stearate 3 Total. Lactose, starch, magnesium stearate and active ingredient are passed through a sieve Jf kk mesh. B and filled into hard gelatin capsules in an amount of RO mg. Example 68. Prepared candles containing 25 mg of active ingredient of the following composition, mg: Active ingredient Glycerides of saturated fatty acid 2000 The active ingredient is passed through a 60 mesh B sieve T and suspended in glycerides of saturated fatty acids previously melted using the minimum necessary of heat. The mixture is then poured into forwarded substituents: atohalo, C, -04-alkyl, cycloalkyl, C-C -alkoxy, benzyloxy or oxygroup, characterized in that the compound of general formula II. (8 HC CC-CHj where R has the indicated values; R - C -, - C 1 alkyl, is reacted with a dialk: salad of common Lormula III (COOR, 3; 2 where R has the specified values in the presence of a base and the compound of the general formula 1U R. T,% g -J "" with TDe R-, R have the indicated values With 50 are cyclized in the presence of acid and the desired product of the general formula (1) is isolated, where R is COOR -rpynpa. About which R is an atom hydrogen or.-alkyl, and / or translate it into a compound of the general Lormula (1), where R is a cyano group, 5-tetrazolyl or -CONHR group, or the desired product of the general formula (1) is isolated, de R phenyl mono- or disubstituted by C-C alkoxy group and / or translate it into a compound of the general Lormula (1), where R is phenyl mono- or disubstituted with an oxy group, and isolate the target duct and / or translate it into the compound of the general formula (1), where R is phenyl, mono- or dysametans of the benzyloxy group, and the desired product is isolated and / or translated into the compound of the general formula (|), where Ry is phenyl, mono or di-substituted benzyloxy. Sources of inhalation taken into account in the examination of P. liderfield. Heterocyclic compounds. M., Izl. Publishing house-1953, t. 1, p. 295.
    权利要求:
    Claims (1)
    [1]
    ' · Claim
    A process for the preparation of 5 "^ 3ameschennyh pyrone of formula 1 · wherein - COOR 3 - group, CONHR ^ -group, a cyano group or 5-tetrazolyl where Q - g water atom or alkyl genus ;
    R is a group of the formula R where m is an integer equal to 0 or 1;
    Z is 0, S, SO, S0 2 or a CO group; R “, - phenyl unsubstituted or substituted by one or two groups selected from 17 substituent substituents: a halogen atom, (C-C4-alkyl, C ^ -C ^ cycloalkyl, C., - C 4 -alkoxy, benzyloxy or wherein the compound of the general formula is an oxy group in that
    U
    HC = C — C — CH3 where R 2 has the indicated meanings;
    R ff - CtC <j - alkyl, is reacted with a dialkyl-R salad of the general Formula Y (C00R ) 2 where R 3 has the indicated meanings, in the presence of a base, and the obtained compound of the general formula 1U where R 2 , And 3 and R 5 have the indicated values are 5 ,
    976850 18 is subjected to cyclization in the presence of an acid and the desired product * of the general formula (1) is isolated, where R 4 is C00R 3 -pynpa, in which R 3 is a hydrogen atom or C ^ -C ^ -alkyl, and / or is converted to the compound of General formula (1), where R 1 is a cyano group, 5-tetrazolyl or -C0NHR 3 -rpynna, or the target product of the general formula (1) is isolated, where R 4 is' phenyl mono- or disubstituted C ^ -C ^ alkoxy group and / or transfer it to the compound of the general Formula (1), where 4 is phenyl mono- or disubstituted by an oxy group, and isolate the desired product and / or transfer it to the compound of the general formula (1), where K 4 is phenyl mono- or disubstituted with a benzyloxy group, and the desired product is isolated and / or converted to a compound of the general formula (]), where R Y is phenyl mono or di-substituted with a benzyloxy group. Information sources,
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    US4335048A|1982-06-15|5-|-8-propyl-4H-1-benzopyran-4-one-2-carboxylic acid
    FR2492378A1|1982-04-23|6-SUBSTITUTED 6H-DIBENZO | PYRANNE DERIVATIVES USEFUL AS ANTI-CELLULAR, IMMUNOMODULATORY AND ANTIVIRAL DRUGS AND METHODS OF THEIR PREPARATION
    同族专利:
    公开号 | 公开日
    RO81048A|1983-02-01|
    FI801020A|1980-10-06|
    AR225918A1|1982-05-14|
    HU184257B|1984-07-30|
    ZA801977B|1981-07-29|
    GR67760B|1981-09-22|
    FR2453168B1|1983-08-12|
    FR2453168A1|1980-10-31|
    IT8048348D0|1980-04-04|
    IL59748A|1983-11-30|
    CH646967A5|1984-12-28|
    ES490122A0|1981-04-01|
    NL8002025A|1980-10-07|
    IE800671L|1980-10-05|
    GB2123814A|1984-02-08|
    GB8312570D0|1983-06-08|
    SE8002515L|1980-10-06|
    GB2047697B|1983-10-19|
    AU5703180A|1980-10-09|
    AT368499B|1982-10-11|
    PL223229A1|1981-01-30|
    YU92080A|1983-02-28|
    PT71050A|1980-05-01|
    CA1142944A|1983-03-15|
    IL59748D0|1980-06-30|
    RO81048B|1983-01-30|
    ES8104268A1|1981-04-01|
    NZ193343A|1982-03-23|
    PL123700B1|1982-11-30|
    GB2123814B|1984-08-01|
    IE49581B1|1985-10-30|
    BE882644A|1980-10-03|
    ATA181880A|1982-02-15|
    DD150002A5|1981-08-12|
    AU535315B2|1984-03-15|
    DE3012597A1|1980-10-16|
    US4364956A|1982-12-21|
    CS214826B2|1982-06-25|
    PH14895A|1982-01-08|
    JPS55133376A|1980-10-17|
    IT1143086B|1986-10-22|
    LU82334A1|1981-12-02|
    GB2047697A|1980-12-03|
    DK142180A|1980-10-06|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4065290A|1975-07-03|1977-12-27|Eli Lilly And Company|Herbicidal β-phenyl-4-piperidinones|
    US4060533A|1976-06-25|1977-11-29|Sandoz, Inc.|Pyranone carboxamides|US4603144A|1984-08-16|1986-07-29|G. D. Searle & Co.|Kojic acid ether-ester derivatives|
    DE3600287A1|1986-01-08|1987-07-16|Bayer Ag|1-ARYLPYRAZOLE|
    JPH0778059B2|1986-03-11|1995-08-23|ダイセル化学工業株式会社|Pyrone-3-carboxamide derivative and herbicide|
    DE3831695A1|1988-09-17|1990-03-22|Hoechst Ag|ELAIOPHYLIN DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR USE AS MEDICINAL PRODUCTS AND MEDICINAL PRODUCTS CONTAINING THE SAME|
    US5650533A|1989-09-11|1997-07-22|Rhone-Poulenc Agriculture Ltd.|Intermediates to herbicidal 4-substituted isoxazoles|
    US5656573A|1989-09-11|1997-08-12|Rhone-Poulenc Agriculture Ltd.|Herbicidal 4-substituted isoxazoles|
    GB8920519D0|1989-09-11|1989-10-25|Rhone Poulenc Ltd|New compositions of matter|
    US5747424A|1989-09-11|1998-05-05|Rhone-Poulenc Agriculture Ltd.|Herbicidal 4-substituted isoxazol|
    DE4031723A1|1990-10-06|1992-04-09|Basf Ag|METHOD FOR PRODUCING ,-UNATURED CARBONYL COMPOUNDS|
    TW587079B|1998-09-25|2004-05-11|Almirall Prodesfarma Ag|2-phenylpyran-4-one derivatives|
    AR029489A1|2000-03-10|2003-07-02|Euro Celtique Sa|PIRIDINES, PYRIMIDINES, PIRAZINAS, TRIAZINES REPLACED BY ARILO, PHARMACEUTICAL COMPOSITIONS AND THE USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT|
    PE20011333A1|2000-03-16|2002-01-16|Almirall Prodesfarma Ag|DERIVATIVES OF 2-FENYLPYRAN-4-ONA AS INHIBITORS OF CYCLOOXYGENASE 2|
    AR036873A1|2001-09-07|2004-10-13|Euro Celtique Sa|PIRIDINAS ARIL REPLACED A, PHARMACEUTICAL COMPOSITIONS AND THE USE OF THE SAME FOR THE PREPARATION OF A MEDICINAL PRODUCT|
    AR037233A1|2001-09-07|2004-11-03|Euro Celtique Sa|PIRIDINAS ARIL REPLACED, PHARMACEUTICAL COMPOSITIONS AND THE USE OF SUCH COMPOUNDS FOR THE PREPARATION OF A MEDICINAL PRODUCT|
    US20090053641A1|2005-03-24|2009-02-26|Kazuyoshi Kuroda|Charge control agent and related art|
    EP1862860A4|2005-03-24|2009-10-21|Orient Chemical Ind|Charge control agent and related technique|
    TW201736529A|2015-12-23|2017-10-16|國家科學及工業硏究協會|Compounds|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB7912063|1979-04-05|
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