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    • 专利摘要:
    Novel 3-(tetrazol-5-yl)-1-azaxanthone and its derivatives, which are shown by the following formula <IMAGE> wherein R1 is hydrogen, amino or hydroxyl; R2 is alkyl, alkoxy, halogen, nitro, carboxyl, hydroxyl, butadienylene (-CH=CH-CH=CH-) which forms a benzene ring with any adjacent carbon atoms or amino group which may be unsubstituted or substituted by at least one alkyl; and m is 0, 1 or 2; and their physiologically acceptable salts, are usable as effective medicines for preventing and/or treating allergic diseases.
    公开号:SU858570A3
    申请号:SU782668856
    申请日:1978-09-25
    公开日:1981-08-23
    发明作者:Нохара Акира；Исигуро Тосихиро；Икава Киеси
    申请人:Такеда Кемикал Индастриз,Лтд (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to the synthesis of new 3- (tetrazol-5-yl) -1-azaxanthone derivatives with formacological activity, which can be used in medicine. A known method for producing tetrazole derivatives by reacting an alkali metal az with the corresponding nitriles I. The purpose of the invention is the synthesis of new pharmacologically active compounds. The aim is achieved by the fact that according to the method of producing 3- (tetrazol-5-yl) -1-azaxone derivatives of the general formula r. Lg in I -, X 1. VI where R. is a hydrogen atom, aiyno or hydroxyl group, alkyl C alkoxy with 1-3 carbon atoms, chlorine, nitro group, carboxyl group, butadiene group (—CH “CH — CH — CH-), which forms a benzene ring with any adjacent carbon atoms, or di () alkylamino, and I1 is an integer of 0.1 or 2, or their salts, the compounds of the formula where R, m have the meanings described above are reacted with alkali azide metal at a temperature of from room temperature to 150s in the presence of Lewis acid with the subsequent isolation of the desired products in the form of free acid or salt. As an example of alkali metal azides, there are alkali metal salts of nitric acid (for example, lithium azide, sodium azl and potassium azide). The reaction can be carried out in an organic solvent. As an example of organic solvents suitable for carrying out this reaction, various hydrocarbons may be mentioned, such as benzene, toluene and petroleum ether; ethers such as tetrahydrofuran, dioxane, diethyl ether and dimethyl ether
    ethylene glycol (dimethyl cellosolve); acetonitrile, dimethylformamide, forms and dimethyl sulfoxide.
    When a salt of nitric acid is used as a reagent, the corresponding compound I is obtained in the form of a salt that corresponds in cation to the nitric acid salt used, and this phenomenon is caused by the acidity of the tetrazole ring. When treated with a suitable acid (for example, a mineral acid such as hydrochloric acid or sulfuric acid), this salt is easily converted into the compound I under consideration, which has free tetrazole. ring. The mutant outside the compound of formula I with an organic amine, alkali metal hydroxide, ammonia or other basic reagent in an ambient manner, i.e. when heated in a suitable solvent, results in the formation of the corresponding salt of compound 1. As examples of such salt-forming reagents may be used organic amines such as ethanolamine, diethanolamine, 0 L-methylephedrine, 1- (3,5-dihydroxyphenyl) -L-izopropilaminoetanol, isoproterenol, dextromethorphan, getrazan (diethylcarbamazine), diethylamine and triethylamine are alkali metal hydroxides, like sodium hydroxide and potassium hydroxide, and ammonia.
    Compound J obtained in this way has anti-allergic activity and are valuable medicines for the prevention (prevention) and treatment of allergic diseases such as allergic asthma, allergic dermatitis and senna fever (vasomotor renitis, also called senvvi rhinitis).
    When using any compound of formula I or a salt thereof for the prophylaxis or treatment of allergic diseases, this compound or its salt can be administered orally to the patient in the same dosage form as tablets, capsules, powders and solutions, usually the daily dose level (total daily dosage is about 1 to about 500 mg per adult.
    These compounds can also be administered in other ways in the form of dosage forms such as solutions for injection, compositions for aerosol inhalation, ointment, etc.
    The compound of formula 11, which is the starting reagent for preparing the target compounds of formula I, can be prepared by the following oOraz.
    So, for example, a compound of formula IV:
    -,
    IV
    ,
    V
    where R306o3Ha4aeT groups, NC-CHj-, R OCOCH2- (where R is an alkyl radical with 1 to 3 carbon atoms) or HOS-CHH - (where X is a halogen atom), which results in the desired starting compound of formula II, As examples of compounds of the formula V, in which RJ is the LdBOCCH - group intended for use in this reaction, methyl cyanoacetate, methyl cyanoacetate and propyl cyanoacetate are used. The reaction of Compound III with Compound I, in which Rj - groups, NC-CHj or R OCOCH, can be carried out in the presence or in the absence of a base. Preferably, the reaction is carried out in a temperature range from room temperature to about 180 ° C and for a period of time from several MINUTES to about 24 hours. Compound II can also be obtained by reacting a compound of formula Ml with a compound of formula V in which R "is an XOC- group CHj, i.e. with cyanoacetyl halide nide (cyanoacetic acid halide) in the presence of substituted formamide. The cyanoacetyl halide used in this reaction may be cyanoacetylchloride cyanoacetyl bromide, cyanoacetyl iodide cyanoacetylfluoride, etc. The substituted formamide used in this reaction may be an alkyl or aryl-substituted formamide, such as N, N-dimethylformamide, N, M-diethyl form. amide, N, N-dipropylformamide, N-methyl-N-ethylformamide, N-methyl-N-phenyl-FOE. amide, N, N-diphenylformamide, etc. This reaction can be carried out in the presence of any one such substituted formamide, i.e. when used as a solvent, the reaction mixture, although, if required, the reaction can be carried out in a mixture of said substituted formamide with another solvent in nature that will not interfere with the reaction. Preferably, the diluent is a conventional organic solvent selected from the group consisting of hydrocarbons, ethers, halogenated hydrocarbons, esters, acetonitrile, and dimethyl sulfoxide. The amount of cyanoacetyl halide used in the preparation of the compound of formula (I) is usually range from about 1 to 10 molar equivalents based on the starting compound of formula III. Although the temperature, time and other reaction conditions are not significant, the reaction is usually water at a temperature in the range of from about to about, for a period of time from about 30 minutes to about 2 days. The proportion of substituted formamide in the reaction mixture is not one of the critical parameters and can be chosen within wide limits However, in most cases asu i.e. formamide is used in the reaction in an amount of about 2 or more molar equivalents based on the molar equivalent of the starting compound 111, Although the starting compound II required for the implementation of the present invention can A compound of the formula II, in which R, a hydroxyl group, can also be obtained by reacting compound II, in which R is an amino group, with an alkali salt of nitrous acid (for example, sodium nitrite or ± potassium ritium) in an aqueous solution of an acid (for example, in an aqueous solution of acetic or hydrochloric acid). Example 1. A mixture of 2 ml of morpholine, 3 ml of dimethylformamide and 10 ml of water is heated to and 1.71 g of powdered 4-oxo-4H-1-benzopyran-3-carbonitrile is added to the solution while stirring, and the procedure for adding this reagent continues no more than 5 minutes The resulting mixture was kept at this temperature for another hour, after which the precipitate formed was collected by filtration. The filter cake is washed with water, recrystallized from acetic acid and washed with chloroform. The result is 1.3 g of crystalline 2-amino-4-oxo-4H-1-benzopyran-3-carboxaldehyde, having so pl. 252-255s (with decomposition). The resulting substance is identified by elemental analysis and nuclear magnetic resonance spectroscopy. NMR spectra were taken out in determinated dimethyl sulfoxide (DMSO-O) cf: iO, 19 (IH, singlet), 9.67 (1.5H, broad singlet), 8.11 (lH, dd, D 2.8 Hz , 7.97-7.80 (MN, multiplet). Elemental analysis.i Found,%: C 63.59, H 3.44, N 7.45, CcNH-N.OS, Calculated,%: C 63.49, H 3.73, N 7.45. The following compounds are synthesized in exactly the same way. Examples of the preparation are given in Table 1. Example 2. A mixture of 217 mg of 2-amino-6-ethyl-4-oxo-4H-1-benzopyran- 3-carboxaldehyde, 300 mg of malononitrile, 5 ml of ethanol and 0.5 ml of piperidine are stirred at reflux for 15 minutes. After cooling the reaction mixture, formed as a slightly soluble crystalline precipitate, the product is separated by filtration and recrystallized from dimethylformide. The procedure will give 160 mg of 2-amino-7-ethyl-1-azaxanone-3-carbonitrile in the form of colorless hollow crystals with mp above The obtained compound is identified by IR and NMR spectroscopy and elemental analysis. IR spectrum of the product in liquid paraffin, 3325, 3125, 2225, 1660. NMR spectrum (c), (f: 9.07 (IH, singlet) , 8.16 (IH, doublet, 3 2 Hz), 7.88 (1H, doublet-doublet) 7.63 (1H, doublet, Hz), 2.92 (2H, quadruplet, Hz), 1.39 ( ZN, triple t, J = 7Hz). Elemental analysis. Found,%: C 67.75, H 4, 01, N16.0, Calculated,%: C 67.91, H 4.18, N 15.84. Examples of the preparation of such compounds are given in table. 2. Example 3. In 40 ml of dimethylformamide, 1.82 g of 2-amino-6-ethIl-4-oxo-4H-1-benzopyran-3-carboxaldehyde is dissolved, after which 3.5 g of cyanoacetylchloride are added to the resulting solution. . The reaction mixture is heated at BO-C for 3 hours with continuous stirring. After this, the solvent is distilled off under reduced pressure and the residue is chromatographed on silica gel. The desired product is isolated from the chloroform eluate and recrystallized from acetonitrile. The result is 1.03 g of 7-ztil-3-cyano-1-azaxanthone, so pl. 183-185С. In tab. 3 shows examples of the preparation of such compounds. Example 4. K70ML of dimethylformamide was added 2.2 g of 2-amino-4-oxo-4H-1-benzopyran-3-carboxal dehyd, after which 2.5 g of cyanoacutane was added to the resulting solution. The reaction mixture is heated by stirring for 15 hours, maintaining the temperature at 140, then the solvent is distilled off under reduced pressure. The residue after distillation of the solvent was chromatographed on silica gel, using chloroform as eluent. The product, taken from the chloroform eluate, is recrystallized from acetonitrile, resulting in a total of 0.83 g of 3-cyano-1-azaxanthone as a crystalline substance with mp. 220-226 C. The resulting compound is identified by NMR spectroscopy and elemental aralia. NMR spectrum taken in deuterated dimethyl sulfoxide (flMCO-dg), rf: 7.4-8.4 (4H, multiplet), 9.10 (1H, doublet, tJ 2 Hz), 9.30 (1H, doublet, 3 2 Hz). Elemental analysis. Found,%: C 70.12, H 2.55, N 12.5. Calculated,%: C, 70.27; H, 2.72; N, 12.61. Examples of the compounds obtained are given in Table. 4. Example 5. To a solution of 0.5 g of 7-isopropyl-2-amino-3-cyano-1-azaxanthone in 80 ml of acetic acid, 1, O, of sodium nitrite at a temperature is gradually added. One hour after the addition of sodium nitrite, 3 ml of water was added to the reaction mixture, which was heated during that hour at the temperature. Thereafter, the solvent was distilled off under reduced pressure, and water was added to the residue. The resulting yellow precipitate is separated by filtration, washed with water and recrystallized from ethanol. 7-isopropyl-2-hydroxy-3-cyano-1-azaxanthone is obtained in the form of a yellow crystalline substance having m.p. above . Elemental analysis. Found: C, 68.28; H, 4.34; N, 9.70. g Calculated,%: C 68.56, H 4.32, N 10.00. Example 6. A mixture of 1.73 g of 2-amino-6-methoxy-4-oxo-4H-1-benzopyran-3-carboxaldehyde, 3.2 ml of ethyl cyanoacetate, 80 ml of ethanol and 1.6 ml of piperidine are boiled in reverse cooler with continuous stirring for an hour. To the resulting mixture was added 3.2 ml of ethyl cyanoacetate and 1.6 ml of piperidine, after which the mixture was heated under reflux for an additional 3 hours. After cooling, the precipitated precipitate was filtered and recrystallized from chloroform-ethanol (2: 1). The result is 1.91 g of ethyl 2-aminot-7-methoxy-1-azaxanthone-3-carboxylate in the form of colorless needle crystals with so pl. 286288 C. The mother liquor remaining after filtration of the precipitate is concentrated, the precipitate formed is separated by filtration and dissolved in chloroform. The resulting chloroform solution is chromatographed on a column of silica gel (14 g). Moreover, the elution is carried out first with a mixture of chloroform-acetone-formic acid (9: 1: 0.1) and then with a mixture of chloroform-acetone-formic acid (2: 1: 0.1 ). Both eluates are combined and concentrated in vacuo to dryness. The residue after evaporation is recrystallized from dimethylformamide-ethanol, resulting in 75 ml of 2-hydroxy-7-methoxy-1-azaxanthone-3-carbonitrile as a white solid with mp. above . The product is identified by infrared and NMR spectroscopy and elemental analysis. NK-spectrum (in vaseline oil): 2250 (stretching vibrations of the CN group), 1680, 1640 cM-t NMR spectrum taken in deuterated trifluoroacetic acid (C FaC 00D)
    (9.20 (IH, singlet), 7.90. (1H), 7.75 (2H, singlet), 4.10 (OTH, singlet
    Elemental analysis (calculated for gross formula): C. .l X 1/4 HgiO.
    Found%: C 61.76, K 2.90, N 10.31
    Calculated,%: C 61.76, H 3.14, N 10.29.
    Example 7 0.50 g of 7-isopropyl-3-cyano-1-aaxanthone is dissolved in 50 ml of dimethylformamide and 0.362 g of sodium azide and 0.282 g of ammonium chloride are added to the resulting solution. The reaction is carried out at a temperature of 120 ° C for 2 hours with continuous stirring. The reaction mixture is then evaporated in vacuo to remove the solvent and 5 ml is added to the residue. water, after which 5 ml of a 5% aqueous solution of sodium nitrite are added to this mixture. The reaction mixture is acidified with 10% hydrochloric acid, the precipitated precipitate is separated by filtration, washed on the filter with water and recrystallized from dimethylformamide. The result is 0.31 g of crystalline 7-isopropyl-3- (1H-tetrazol-5-yl ) -1-azaxanthone having a melting point of 275-277 | C (the product melts with decomposition, which is accompanied by foaming). The compound obtained is identified according to NMR spectroscopy.
    NMR spectrum1 (in DMSA - d), rf: 1.30 (6H, doublet, 3 7 Hz), 3.00 (1H, quintet, 3 7 Hz), 7.70 (1H, doublet Hz), 7, 90 (1H, doubled duplicate Dv 2, Over 8), 8.03 (1H, doublet), 9.15 (1H, doublet), 9.38 (1H, doublet).
    The following compounds are synthesized in the same way: 3- (1H-Tetrazol-5-yl) -1-azaxanthone, m.p. above 300 ° C;
    7-Ethyl-3- (1H-tetrazol-5-yl) -1-azaxanthone,
    m.p. 262-265 seconds (decomposes with foaming);
    7-Isopropyl-2-amino-3- {1H-tetrazol-5-yl) -1-azaxanthr, m.p. ,
    7-Isopropyl-2-hydroxy-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. 300 ° C;
    7,9-Dimethyl-3- (1H-tetrazol-5 yl) -1-azaxanthone, m.p. 294-298 seconds;
    7-tert. Butyl-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. 273-275 "with;
    7-Iopropoxy-3- (1H-tetrazol-5-yl) -1-azaxanthone, so pl. 271-272 ° C;
    7-Chloro-3- (1H-tetrazol-5-yl) -1-azaxanthone,
    m.p. above 300 ° C, 3- (1H-Tetrazol-5-yl) -benzo (h) -1-azaxanthone, so pl. 291-293 C (decomp.);
    9-Methoxy-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. above ZOO ° C.
    Example 8. In 150 ml of ethanol, 2.0 g of 6-chloro-2-amino-hro5 mon-3-carboxaldehyde was suspended, after which 1.3 g of malononitrile and 5 ml of piperidine were added to this suspension with stirring. The resulting mixture was refluxed for 2 hours. Then the reaction mixture was evaporated under reduced pressure, and all substances boiling to 100 ° C were distilled off. 50 ml of dimethylformamide was added to the residue, and then yogt 0.5 g of sodium azide and 0.4 g of ammonium chloride were added. The reaction is carried out under continuous stirring conditions for 2 hours. At the end of this time, the solvent is distilled off under reduced pressure. The residue is diluted with water, treated with 6 ml of 10% aqueous solution of sodium nitrite and acidified with 10% hydrochloric acid. The precipitate formed is filtered off, washed on the filter with water and the ne 5 recrystallized from dimethyl form. The result is 7-chloro-2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone as a crystalline substance with mp. above .
    Q The following compounds are synthesized in the same way:
    7-Nitro-2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. above 300 ° C;
    5 9-Methoxy-2-amino-3- (1n-tetrazol-5-yl) -1-azaxanthone, m.p.
    8-hydroxy-2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone,
    m.p. zoo ° s;
    0 Benzo (h) -2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. ,
    7-dimethylamino-2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone, 5 m.p. above 300 ° C;
    7,9-Dimethyl 2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone, m.p. 300 ° C.
    Example 9. To a solution of 0.163 g of p-7-isopropyl-2-amino-3- (1H-tetrazol-5-yl) -1-azaxanthone in 20 ml of methanol was added 0.1 g of diztanolamine and the mixture was heated at bSRC for 10 min
    After cooling, the precipitated crystals are separated by filtration and recrystallized from methanol. In the end, get the target diethanolamine the salt of 7-isopropyl-2-amino-3- (1n-tetrazol-5-yl) -1-azaxanthone in the form of colorless needle crystals with so pl. above .
    In a similar manner, the 7-isopropyl-3- (1H-tetrazol-5-yl) -1-azaxanto5 dimethanummonium salt is synthesized. 149-15lc. 11. Starting compound 6-Methyl-4-oxo-4H-1-benzopyran-3-carbonitrile b-Ethyl-4-oxo-4H-1-benopyran-4-carbonitrile 6-Chloro-4-oxo-4H-1-benzopyran -3-carbonitrile 6-methoxy-4-oxo-4H-1-benzopyran-3-carbonitrile .... "-...." a b, 8-dimethyl-4-oxo-4H-2-benzopyran-3 7-hydroxy-4-oxo-4H-1-benzopyran-3-carbonitrile-6-nitro-4-oxo-4H-1-benzopyran-3-carbonitrile 6-isopropyl-4-oxo-4H-1-benzo pyran-carbonitrile 6-n-Butyl-4-oxo-4H-2-benzopyran-3-carbonitrile 3-carbonitrile 8-methoxy-4-oxo-4H-1-bis-pyran-3-carbonitrile 3-Cyano-6eH3o (f) -chromone 6-Dimethylamino-4-oxo-4H-1-benzopyran-3-carbonitrile b-tert. Butyl 4-oxo-4H-1-benzopyran-3-carbonitrile 6-IZOPROPOXI-4-OXO-4H-1-benzopyran-3-carbonitrile 85857012 Product | mp C (recrystallization solvent) 2-amino-6-methyl -4-282-284 -oxo-4N-1-benzopy-Acetic acid, acid-3-carboxaldelota-2-amino-6-ethyl-4-ca-246-249 (decomp.) So-4K-1-benzopyran- Acetone-3-carboxaldehyde 2-amino-6-z lor-4-ca-308-310 (decomp.) With co-4H-1-benzopyran-acetic acid-3-carboxaldehyde 2-amino-6-methoxy-4-251 -254 (dec.) -Oxo-4H-1-benzopyran-chloroform-3-carboxaldehyde. - -. - - - - - - - ".. - -.". - -. "-, ..." ™ in,.,., ... ".." 2-Amino-6,8-dimethyl-4-259-263 (decomp.) -Oxo-4H-1- benzopyran-acetic acid-3-carboxaldehyde 2-Amino-7-hydroxy-4-oxo-297-300 (decomp.) -4H-1-benzopyran-3-Acetic acid-carboxaldehyde 2-Amino-6-nitro-4- 290-293 (decomp.) -Oxo-4N-1-benzopyran-Muravina sour-3-carbsyl saldegidt 2-Amino-b-isopropyl-4- 206-208-oxo-4H-1-benzopyran-Acetic acid-3- 2-Amino-6-n-butyl-4-220-222-oxo-4H-1-benzopyran-acetic acid-3-carboxaldehyde 2-amino-8-methoxy-4-235-238-oxo-4N-1 carboxaldehyde -benopyran-Chloroform -3-carboxaldehyde 2-Amino-benzo (f) -chro-258-260 (razlomemon-3-carboxal De-pheny with foaming) 2-Amino-6-dimethylamino-276-280 (with decomposition-4-oxo-4H-1-benE O-deposition) of wounds-3-carboxaldehyde Chloroform methanol 2-Amino-6-tert.butyl-240 -242 -4-oxo-4H-1-benzopyran-acetic acid-3-carboxaldehyde 2-amino-6-isopropoxy-4-218-219-oxo-4H-1-benzopyran-chloroform-3-carboxaldehyde Table Acetic acid 13 The starting compound 2-Amino-4-oxo-4H-1-6enzopyran-3-carboxaldehyde 2-A1 "1io-b-chloro-4-oxo-4H-1-beisopyran-3-car- -. Boxaldehyde 2-Amino-b-dimeti: lamino-4-oxo-4H-1-benzopyran-3-carboxaldehyde 2-amino-6-isopropyl-4-oxo-4H-1-benzopyran-3-carboxaldehyde 2-amino-6 -methyl-4-oxo-4H-1-benopyran-3-carboxaldehyde 2-Amino-8-methoxy-4-oxo-4H-1-benzopyran-3-carboxaldehyde 2-AMHHO-6eH3o (f) -chromone 3-carboxaldehyde The original compound 2-Amino-6-methyl-4-oxo-4H-1-benzopyran-Z-carboxald guide 2-Amino-4-oxo-4H-1-benzopyran-3-carboxaldehyde 2-Amino-6-isopropyl-4 -oxo-4H-1-benzopyran-3-carboxaldehyde 2-AMINO-6-HLOR-4-OXO-4H-1-benzopyran-3-carboxaldehyde, iliglmt h1 | "2-amino-6,8-dimethyl-4- Kso-4H-1-benzopyran-3-carboxaldehyde 2-A1 1ino-6-tert. butyl-4-oxo-4H-1-benzopnran-3-carboxaldehyde .. “.“.-. - ...-- -.------ 858570 14 Taolitsa 2 Product ITl., S / Solvent I for recrystallization of 2-Amino-1-azaxan-300 ton-3-carbonitrile Dimethylformamide 2-Amino-7-chloro-1-aza - 300 xanthone-3-carbonyte-Di1 etylformamdyl 2-Amino-7-dimethylammonium-300 -1-azaxanthone-3-carvo- Ethanol nitrile 2-amino-7-isopropyl-3-300-cyano-1-azaxanthone Dimethylformamide 7 -Methyl-2-amino-3-cya-300 no-1-azaxaitone Dimethylformamide 9-Methoxy-2-g mino-3 - cyano-1-azaxanthone 300 Dimethylformamide 2-Amino-3-cyano-bvn-300 (f ) -1-azaxanthone Dimethylformamide Table 3 I Product I Mp. C Solvent I for recrystallization of 7-Cometil-3-cyano-240-242 -1-azaxanthone Ethanol Z-Cyano-1-azaxan-220-226 tons Ethanol 7-Isopropyl-3-cya-203-205 no-1-azaxanthone Ethanol, 7-Chloro-3-cyano-1- 286-288-azaxanthone Dimethylformamide col I1ShG1I - D-yy - ™ 7,9-Dimethyl-3 -cyano- 254-257 -1-azaxanthone Acetonitrile 7-Gret. Butyl-3-cyano-247-249 -1-azaxanthone Acetonitrile ------ ----- --------------- ---------
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining derivatives of 3- (tetraeol-5-yl) -1-azaxanthone total
    formulas * ___ 0 IL40 Wd οςυ 0 k 45 where - atom hydrogen amino or
    hydroxyl group, R 2 is alkyl. C ^ -Cl, alkoxyl with the number of carbon atoms 1-3, chlorine, nitro group, carboxyl group, hydroxyl group, buta-JQ diene group (-CH = CH-CH "CH *), which forms a benzene ring with any adjacent atoms carbon, or di (SS ") alkylamino, am represents an integer of 0.1 or 2,
    or their salts About l tea with i the fact that compound of the formula I / O 'sn 1 0 Where R,, R 4 andmatter ohara- therized above
    subjected to interaction with an alkali metal azide at a temperature from room temperature to 150 ° C. in the presence of a Lewis acid, followed by isolation of the desired products in the form of a free acid or salt.
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    JPS5825677B2|1983-05-28|
    DE2841644A1|1979-04-05|
    NL188579B|1992-03-02|
    ES473680A1|1979-04-16|
    NL188579C|1992-08-03|
    FR2404011B1|1981-08-14|
    GR64802B|1980-06-02|
    FR2404011A1|1979-04-20|
    US4267332A|1981-05-12|
    IT7827984D0|1978-09-22|
    GB2004551B|1982-03-10|
    DK156725B|1989-09-25|
    NL7809741A|1979-03-28|
    JPS5448798A|1979-04-17|
    DE2841644C2|1989-09-21|
    AU522242B2|1982-05-27|
    NO149964C|1984-07-25|
    ATA685478A|1980-07-15|
    AT360988B|1981-02-10|
    BE870736A|1979-03-26|
    HU178360B|1982-04-28|
    GB2004551A|1979-04-04|
    CH638525A5|1983-09-30|
    DK418678A|1979-03-27|
    AU3948878A|1980-03-06|
    ZA785054B|1979-08-29|
    NO783233L|1979-03-27|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    GB1403487A|1972-07-21|1975-08-28|Yoshitomi Pharmaceutical|Heterocyclic substituted alkanoic acids and derivatives|
    NL7403583A|1973-03-19|1974-09-23|
    JPS576433B2|1973-06-26|1982-02-04|
    JPS5516432B2|1974-05-28|1980-05-01|JPH0588236B2|1985-01-28|1993-12-21|Takeda Chemical Industries Ltd|
    JPH0588237B2|1985-03-20|1993-12-21|Takeda Chemical Industries Ltd|
    US5831117A|1995-01-20|1998-11-03|G. D. Searle & Co.|Method of preparing retroviral protease inhibitor intermediates|
    JPH08325248A|1995-05-26|1996-12-10|Chugoku Kayaku Kk|New reagent for synthesizing tetrazole compound and production of tetrazole compound using the same|
    US5952338A|1996-07-05|1999-09-14|Takeda Chemical Industries, Ltd.|Agent for prophylaxis and treatment of disturbance of visual function|
    US7268454B2|2003-01-17|2007-09-11|Magnetic Torque International, Ltd.|Power generating systems|
    US10214536B2|2016-01-29|2019-02-26|The Regents Of The University Of Michigan|Amlexanox analogs|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    JP52115817A|JPS5825677B2|1977-09-26|1977-09-26|
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