• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Compounds of the formula <IMAGE> or of a hydrochloric or hydrobromic acid addition salt thereof, in which R1 is hydrogen or methoxy, and R2 denotes benzoyl, furoyl, thienylcarbonyl, alkoxycarbonyl having 2 to 5 carbon atoms or (2-hydroxyalkoxy)carbonyl having 4 or 5 carbon atoms, are prepared in accordance with a novel process. Initially, a 2-chloro-6,7-dimethoxyquinazoline or a 2-bromo-6,7-dimethoxyquinazoline, whose amino group situated in the 4 position is substituted, is reacted, in an inert organic solvent and at 50-200 DEG C, with a corresponding piperazine. In a second reaction step, the substituents of the amino group are removed by hydrogenolysis. The compounds which are obtained can be used as agents for lowering blood pressure.
    公开号:SU1033002A3
    申请号:SU772497901
    申请日:1977-06-14
    公开日:1983-07-30
    发明作者:Дитрич Хэммен Филип
    申请人:Пфайзер Инк (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a new half-sieves method (2-fupoyl) piperazik-1 -nnl-i aMMHO-6,7 flnMeTOK of chiinazoline of formula 1 IyOtllsO V fl -.h where R is furoyl, or its hydrochloride or hydrobromide salt, which is e with a hypotonic agent, and can be used in medicine. A known method for the preparation of (.2-furoyl) piperazin-1-yl-amyo6, 7D-me7oxyquinazoline of formula 1, which is in that 2, -dichloro 0, chetoxynequinazoline is reacted with ammonia to form 2-chloro-amino. -6.7 dimethoxy nazolin is reacted with 1-ethoxycarbonylpiperazine, with the following reaction resulting in the formation of a state product with water, and the resulting 2- (piperazin-i-yl) -amino-6,7-dimethoxyquinazoline is reacted with furoyl chloride 1. The disadvantage of this method is the multistage. The purpose of the invention is to simplify the process. The goal is achieved by a new method of obtaining a compound of the formula, which implies that 1 mole of the compound of the formula i I eHzO - .. in dHaO-vX lf I H -., Where X is a chlorine or bromine atom, R 2 is COCg H 5 or -COORa 5 -w / xf, where RS, is C -C, 1 1 14. and reacted with 2 moles of the compound of the formula I I I,,:. where RJ has the indicated value, in an inert solvent at a temperature of 50-200 0, and the target product is isolated in free form or in the form of its hydrochloride or hydrogen hydrobromic salt. In addition, the process is carried out at 80-130 ° C. Alkanols, such as isopropanol, butanol, isobutanol, isoamyl alcohol, 2-methyl-2-pentanol and 3,3-dimethyl-1-butanol, glycols such as ethylene glycol and diethylene glycol, glycol ethers such as ethylene glycol monomethyl ether, diethylene glycol monoethyl ether, 1,2-dimethoxyethane and diethylene glycol dimethyl ether; tertiary amides, such as N, N-dimethylformamide, L, M-diethylacetamide and methylpyrrolidone; dimethyl sulfoxide or pyridine. EXAMPLE 1. Preparation of (2-furoyl) -piperazin-1-ylD-4-amino-6.7 dimethoxyquinazoline. Into a 50 ml flask equipped with a stirrer, a reflux condenser and a drying tube, 1 bO MP (0.66 mol) of 4-benzoylyamio-2 chloro-6, 7-dimethoxyquinazoline, 2 mg (1.32 mmol) 1- (2 furoyl) piperazine and ml of isoamyl alcohol. The resulting mixture is heated at h, then cooled to room temperature. The precipitated solid is separated by filtration and dried, yielding 60 mg of crude product. This product is identified as (2-furoi5) -piperazin-1yl-α-amino-b, 7-dimethoxyquinazoline using thin-layer chromatography with silica gel column and using an ethyl acetate-diethylamine system as a eluent in a ratio of 90:10. This product is purified in a 0.59 inch (12.7228., 6 mm) column filled with silica gel, eluting with a solvent system of benzene / acetone / formic acid / water in a volume ratio of 100: 100: 20: 5. Moreover, ltvJ | 4i-r | I | lXl liriltft W tVV7 C.Vr "J" ril./ri4r obtain 35 mg of the desired product with mp, 275 ° C. Carrying out the procedure described above, but using the indicated solvent instead of isoamyl alcohol and wire reactions using the temperatures and times indicated in the table, the desired compound is obtained in the same way. PRI mme R 2. Preparation of (2-furoyl) piperazin-1-yl3-2-amino6, 7-dimethoxyquinazoline. In the reaction flask mix 2.0 g (0,0064 mol) -ethoxycarbonylamino-2-chloro-6, 7-Dimethoxyquinazoline and 23 ml of isoamyl alcohol. To the mixture is added with a solution of 1 -: (2-furoyl) piperazine (2.5 g, 0, OH mol) in 15 ml of isoamyl alcohol, and the mixture is heated at k c. The precipitated solid is separated in a filter funnel, washed with iso-amyl alcohol, then mixed with 100 ml of a 10% aqueous solution of sodium hydroxide. An aqueous solution of chloroform is added, and the mixture is stirred for 15 minutes. The organic layer was separated, evaporated to give about 25 ml, and 50 ml of tetrahydrofuran was added. The solids are recovered by filtration and then purified by chromatographic separation in a column filled with silica gel (K 18 inches, 25,, 2 mm), with elution first with ethyl acetate and then with methanol. The fractions containing the desired compound are collected and evaporated to dryness. The precipitate is dissolved in 10 ml of chloroform, hexane is added to the cloud point, stirred for 15 minutes and the resulting crystals are separated by filtration.
    Melting point of crystalline product, yield 900
    (37%).
    . The above reaction is repeated at 18 hours; however, the results remain virtually unchanged.
    2-methyl-2-pentanol
    Diet ilen gly col
    2
    130
    0.25,200
    权利要求:
    Claims (2)
    [1]
    1. The method of obtaining 2- £ 4- (2-furyl) -piperazin-1-yl /] - 4-amino-6,7-dimethoxyquinazoline of the general formula where is furoyl, or its hydrochloride or hydrobromide salt based on derivative 6, 7-dimethoxyquinazoline, characterized in that, in order to simplify the process, as a derivative of 6,7-dimethoxyquinazoline take 1 mol of a compound of the general formula pi) N where X is chloro or bromo;
    8 2 —COS 6 H B or —COOR 3 , where R ^ —Cjf —Cph is alkyl, and is reacted with 2 mol of a compound of the general formula
    V .. and / where R ^ has the indicated value.
    4 In an inert solvent at 50-200 ° C, and the target product is isolated in free form or in the form of hydrochloric or hydrobromic salt.
    [2]
    2. The method according to p. 1, about t and h and y - 1 and the second with the fact that the process is carried out at 80-130 ° C.
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    同族专利:
    公开号 | 公开日
    JPS5543465B2|1980-11-06|
    EG12922A|1980-03-31|
    SU946402A3|1982-07-23|
    BG35747A3|1984-06-15|
    YU40164B|1985-08-31|
    AU2558377A|1978-09-07|
    CS202069B2|1980-12-31|
    NO147838B|1983-03-14|
    SE450120B|1987-06-09|
    GR72288B|1983-10-17|
    DD131021A5|1978-05-24|
    PT66617A|1977-06-01|
    CA1068698A|1979-12-25|
    SE7705745L|1977-12-16|
    YU132677A|1982-08-31|
    FI771741A|1977-12-16|
    HU177883B|1982-01-28|
    ZA773014B|1978-04-26|
    RO77330A|1981-06-22|
    SE8107554L|1981-12-16|
    PT66617B|1978-10-27|
    IL52167D0|1977-07-31|
    FR2355015A1|1978-01-13|
    IL52167A|1981-01-30|
    NZ184168A|1979-08-31|
    DK240877A|1977-12-16|
    PL105558B1|1979-10-31|
    PL111221B1|1980-08-30|
    CH638516A5|1983-09-30|
    PL113012B1|1980-11-29|
    FI66853B|1984-08-31|
    AR218251A1|1980-05-30|
    BE855656A|1977-12-14|
    HK31481A|1981-07-10|
    RO73050A|1981-08-30|
    PH22196A|1988-06-28|
    SE435380B|1984-09-24|
    JPS52153985A|1977-12-21|
    BG35594A3|1984-05-15|
    NL172543B|1983-04-18|
    IE45423B1|1982-08-25|
    NL172543C|1983-09-16|
    CH638203A5|1983-09-15|
    CH638517A5|1983-09-30|
    GB1548856A|1979-07-18|
    IE45423L|1977-12-15|
    NL7705939A|1977-12-19|
    DK146625B|1983-11-21|
    NO771919L|1977-12-16|
    FR2355015B1|1981-07-24|
    RO77308A|1981-08-17|
    ATA386977A|1979-09-15|
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    DK146625C|1984-06-04|
    MY8100270A|1981-12-31|
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    DE2725019A1|1977-12-22|
    NO147838C|1983-06-22|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3511836A|1967-12-13|1970-05-12|Pfizer & Co C|2,4,6,7-tetra substituted quinazolines|
    US3669968A|1970-05-21|1972-06-13|Pfizer|Trialkoxy quinazolines|
    JPS4966691A|1972-10-30|1974-06-27|
    US3935213A|1973-12-05|1976-01-27|Pfizer Inc.|Process for hypotensive 4-amino-2- quinazoline derivatives|
    JPS50126682A|1974-03-25|1975-10-04|DE3346675A1|1983-12-23|1985-07-04|Beiersdorf Ag, 2000 Hamburg|SUBSTITUTED 1--4- CYCLOHEXENYL DERIVATIVES OF PIPERAZINE AND HOMOPIPERAZINE, METHODS FOR THE PRODUCTION THEREOF, AND THEIR USE, AND ITS RELATED PRODUCTS|
    AT384218B|1985-12-04|1987-10-12|Gerot Pharmazeutika|METHOD FOR PRODUCING NEW CHINAZOLINE DERIVATIVES|
    CA2077252C|1992-08-31|2001-04-10|Khashayar Karimian|Methods of making ureas and guanidines, and intermediates therefor|
    US5654307A|1994-01-25|1997-08-05|Warner-Lambert Company|Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family|
    IL112249A|1994-01-25|2001-11-25|Warner Lambert Co|Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds|
    IL112248D0|1994-01-25|1995-03-30|Warner Lambert Co|Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them|
    US5932538A|1996-02-02|1999-08-03|Nitromed, Inc.|Nitrosated and nitrosylated α-adrenergic receptor antagonist compounds, compositions and their uses|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US69620176A| true| 1976-06-15|1976-06-15|
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