• 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:
    A process for preparing an ergoline of the formula wherein Cs = C10 is a CC single or double bond, R' is a hydrogen or CONR2, R being hydrogen, methyl, or ethyl, and wherein NR' is in the a- or β-position, R2 is lower alkyl of up to 3 carbon atoms, and the salts thereof, comprises treating the corresponding ergolinyl carboxylic acid amide with lead (IV) acetate in an aprotic polar solvent; reacting the intermediarily formed corresponding isocyanate with water or with a reactive amine of up to 4 carbon atoms, (e.g. a mono- or dialkylamine of up to 4-C atoms); and, optionally, treating the resultant product with an acid to form the corresponding salt.
    公开号:SU1272988A3
    申请号:SU823470940
    申请日:1982-08-03
    公开日:1986-11-23
    发明作者:Зауер Герхард；Хаффер Грегор
    申请人:Шеринг Аг (Фирма)；
    IPC主号:
    专利说明:


    CM. The invention relates to an improved method for producing ergolins of the general formula eoyn, where R is hydrogen or a CON (X) j residue with X being ethyl, and the NHR group can be in the oi or p position; Rj is lower alkyl having 1-3 carbon atoms, C | p is a simple or carbon-carbon double bond, or their physiologically acceptable salts, which are valuable pharmacologically active compounds and also serve as intermediates in the synthesis of those. I The aim of the invention is to create an enhanced method of obtaining ergoline compounds, allowing to expand the range of target products and increase the stereoselectivity of the process, which is achieved by treating the corresponding amgreen carbonyl acid with lead acetate. (Iv) in the presence of anhydrous alkali metal carbonate or alkaline earth metal. Example 1. 534.6 ml of isomeric acid amide (2 mmol) are dissolved in 1 O ml of dimethylformamide. After adding 0.6 g of potassium carbonate while cooling with ice water, 1.8 g of lead (IV) acetate (98%, A mmol) are introduced in portions into the reaction mixture in portions over 3 minutes, stirred for 5 minutes, and 8 ml of freshly distilled dimethylamine. After 10 minutes, the reaction solution was diluted with 50 ml of methylene chloride and washed twice with 10 m 1 of 6% aqueous ammonia solution and an additional 500 ml of water. Dried on magnesium sulfate and one stripped off the organic phase is filtered on 50 g of alumina (neutral, activity step), and eluted with methylene chloride - ethyl acetate 80:20. . The residue which remains after evaporation, which consists of 3- (9,10-didehydro-6-methyl-8p-ergolinyl) -1,1-dystilurea, is dissolved in 10 ml of ethanol. a solution of 0.25 g of maleic acid in 5 ml of ethanol is added, evaporated by 2/3 volume and left to crystallize after seeding the crystals overnight in a refrigerator. 0.51 g of 3- (9,10-dehydro-6-methyl-8-ergolinyl) -, 1-dystilurea hydroxide is isolated. with 0.5 (methanol). Example2. 267.3 ml of an isothermal acid amide (1 mmol), as in Example 1, are reacted with lead (IV) acetate. The reaction mixture is then carefully introduced into 25 ml of 1N sulfuric acid, which is preheated to 85c, further stirred for 5 minutes, after cooling, mixed in portions with 2 g of sodium bicarbonate and, after addition of 25 ml of methylene chloride, it is stirred for 15 minutes. min The entire reaction solution is filtered through kieselguhr, the aqueous phase is extracted twice with 20 ml of methylene chloride. The residue after evaporation of the combined methylene chloride phases is filtered with a meta-mixture. NOL - water 95: 5 through silica gel. 84 mg of 9.1 O-didehydro-6-methylergoline-8 (x1-amine. My,, 5 (pyridine) are obtained. Example 3. Analogously to Example 1, 295 mg of Amide 9, U-didehydro-b-} -propyl-86- ergolincarboxylic acid is reacted with lead (IV) acetate to form an isocyanate that reacts with diethylamine to form the corresponding urea. After the treatment, 120 mg of 3- (9.10-Å) is obtained according to chromatography on alumina using a mixture of methylene chloride and ethyl acetate. Didehydro-6-n-propyl-8-cC-ergolinyl) -1, 1-diethyl urea. Preparation of starting material. From 3.1 g of methyl sephira. 9,10 didehydro-bH-prop: il-8 | 6-ergoline-carboxylic acid by keeping the mixture in isomeric amides by settling in an ammonia solution in ethylene glycol, from which 1.2 g of 9,10-didehydro-6- is separated by chromatography. I-propyl-8c (.-Ergolincarboxylic acid. Md + 297 °, 5 (pyridine). EXAMPLE 4 ,
    权利要求:
    Claims (1)
    [1]
    The claims 1. The method of producing ergolim
    where R - hydrogen or the residue CON (X) t at X - ethyl, and the corpse na NHR, may be in оС - or / 1 position; - the lowest. alkyl having 1-3
    carbon atom, C 9 ......
    . , C, 0 is a simple or double carbon-carbon bond., Or their physiologically acceptable salts from the reactive derivatives of ergolinyl carboxylic acids through the formation of an intermediate isocyanate, characterized in that, in order to simplify the process and expand the range of target products, the ergolinyl carboxylic amide of the general formula
    HH where R 2 has the indicated meanings, in an aprotic solvent such as dimethylformamide, is treated with lead (IV) acetate in the presence of anhydrous alkali metal or alkaline earth metal carbonate and then reacted with water in the presence of acid or diethylamine, after which, if necessary using a physiologically acceptable acid, they are converted to the corresponding salt.
    VNIIIPI Order 6353/59 Circulation 379 Subscription
    Custom polygr. ave, city of Uzhhorod, st. Project, 4
    类似技术:
    公开号 | 公开日 | 专利标题
    ES2562080T3|2016-03-02|Process and intermediate compounds to prepare integrase inhibitors
    CA2191647C|2005-01-25|Process improvement in the synthesis of n-[3-|phenyl]-n-ethylacetamide
    SU691089A3|1979-10-05|Method of producing carbonyl-substituted 1-sulphonylbenzimidazoles
    DK159680B|1990-11-19|CYCLIC IMIDES USED FOR THE PREPARATION OF CYCLIC AMINO ACIDS
    SU1272988A3|1986-11-23|Method of producing ergolines or physiologically acceptable salts thereof
    IE59396B1|1994-02-23|Process for the preparation of 2-alkoxy-n-|octan-3-yl)amino-benzamides
    EP0080819B1|1985-01-16|11-0-alkylerythromycin a derivatives
    KR920002295B1|1992-03-21|Process for the preparation of pyrrolidone derivatives
    Tamura et al.1973|Novel syntheses of thiazolo [3, 2‐b]‐s‐triazoles
    GB2036744A|1980-07-02|Eburnane derivatives
    US3758546A|1973-09-11|Methoxy amine derivatives and process for preparing them
    SU532340A3|1976-10-15|The method of obtaining 3- | - triazolo | pyridazines or their salts
    JP2578797B2|1997-02-05|Method for producing N- | formamides
    SU922108A1|1982-04-23|Process for producing derivatives of 6-methyl-8-beta-hydrazinomethylergolin or their salts
    KR19990008411A|1999-01-25|Improvement method of 4-hydroxy-2-pyrrolidone
    US4189444A|1980-02-19|Process for the preparation of N,N'-disubstituted 2-naphthaleneethanimidamide and intermediates used therein
    US5643438A|1997-07-01|Process for the preparation of substituted diamino-dicarboxylic acid derivatives
    US4062891A|1977-12-13|N-formyl-2,3,5,6-dibenzobicyclo[5.1.0]octan-4-methylamine
    JP2771257B2|1998-07-02|Preparation of imidazole derivatives
    US7544802B2|2009-06-09|Process for the preparation of 2-|-tropane derivatives
    SU1189351A3|1985-10-30|Method of producing 5'-s-|-peptidergotalkaloid or its additive salts with acids
    US3751462A|1973-08-07|Process for preparation of substituted fluoromethanesulfonanilides
    SU469251A3|1975-04-30|The method of obtaining heterocyclic compounds
    SU382622A1|1973-05-25|METHOD FOR PREPARING -A1U1INO-OR-Y-OXISAL ^ SECONDED HETEROCYCLIC COMPOUNDS
    US3842086A|1974-10-15|Process for the preparation of substituted or unsubstituted pyridines
    同族专利:
    公开号 | 公开日
    HU186969B|1985-10-28|
    IE53437B1|1988-11-09|
    DE3261963D1|1985-02-28|
    YU199282A|1985-03-20|
    EP0074921A1|1983-03-23|
    CS642282A2|1985-07-16|
    CS241122B2|1986-03-13|
    AT11289T|1985-02-15|
    AU555576B2|1986-10-02|
    GR76897B|1984-09-04|
    ES515428A0|1983-05-01|
    JPH0239511B2|1990-09-05|
    DD203544A5|1983-10-26|
    US4748248A|1988-05-31|
    DE3135305C2|1983-07-21|
    DE3135305A1|1983-03-10|
    DK161646B|1991-07-29|
    IL66679A|1986-04-29|
    IL66679D0|1982-12-31|
    EP0074921B1|1985-01-16|
    DK161646C|1992-01-06|
    ES8305361A1|1983-05-01|
    CA1175813A|1984-10-09|
    DK368382A|1983-03-04|
    JPS5855483A|1983-04-01|
    AU8786382A|1983-03-10|
    IE822156L|1983-03-03|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    EP0021206B1|1979-06-13|1983-06-22|Schering Aktiengesellschaft|-n', n'-diethyl urea derivatives, their preparation and pharmaceutical compositions containing them|DE3151912A1|1981-12-23|1983-06-30|Schering Ag, 1000 Berlin Und 4619 Bergkamen|NEW ERGOLIN AMINO DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINAL PRODUCTS|
    DE3309493A1|1983-03-14|1984-09-20|Schering AG, 1000 Berlin und 4709 Bergkamen|NEW ERGOLIN DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND USE AS A MEDICINAL PRODUCT|
    CH666035A5|1984-12-24|1988-06-30|Sandoz Ag|8-ALPHA ACYLAMINOERGOLENE.|
    DE3915950A1|1989-05-12|1990-11-15|Schering Ag|8ACYLAMINO ERGOLINE, THEIR PRODUCTION AND USE AS A MEDICINAL PRODUCT|
    US20060171795A1|2005-01-28|2006-08-03|Cromwell Stephen D|Substantial embedment of metallic debris|
    JP2010119349A|2008-11-20|2010-06-03|Shinichi Okamoto|Method for producing processed cereal flour food product such as instant bread|
    EP3253753A4|2015-01-20|2018-06-27|Xoc Pharmaceuticals, Inc|Ergoline compounds and uses thereof|
    MX2017009406A|2015-01-20|2018-01-18|Xoc Pharmaceuticals Inc|Isoergoline compounds and uses thereof.|
    AU2018275873A1|2017-06-01|2019-12-19|Xoc Pharmaceuticals, Inc.|Ergoline derivatives for use in medicine|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE3135305A|DE3135305C2|1981-09-03|1981-09-03|Process for the production of 8-ergolinyl ureas|
    [返回顶部]