JPH0215544B2 - - Google Patents
Info
- Publication number
- JPH0215544B2 JPH0215544B2 JP55010182A JP1018280A JPH0215544B2 JP H0215544 B2 JPH0215544 B2 JP H0215544B2 JP 55010182 A JP55010182 A JP 55010182A JP 1018280 A JP1018280 A JP 1018280A JP H0215544 B2 JPH0215544 B2 JP H0215544B2
- Authority
- JP
- Japan
- Prior art keywords
- sulfonamide
- intermediate product
- acid
- phenylethylamine
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 20
- 229940124530 sulfonamide Drugs 0.000 claims description 14
- 239000013067 intermediate product Substances 0.000 claims description 12
- 229940100389 Sulfonylurea Drugs 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 5
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 5
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- -1 5-substituted-isoxazole 3-carboxylic acid residue Chemical group 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 230000009435 amidation Effects 0.000 description 3
- 238000007112 amidation reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FXNSVEQMUYPYJS-UHFFFAOYSA-N 4-(2-aminoethyl)benzenesulfonamide Chemical compound NCCC1=CC=C(S(N)(=O)=O)C=C1 FXNSVEQMUYPYJS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical compound NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 description 1
- XMVNMWDLOGSUSM-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=NO1 XMVNMWDLOGSUSM-UHFFFAOYSA-N 0.000 description 1
- MLUXXYJYCQANRP-UHFFFAOYSA-N 5-methyl-n-(2-phenylethyl)-1,2-oxazole-3-carboxamide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC=CC=2)=N1 MLUXXYJYCQANRP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- IAERAFZPWNQKDJ-UHFFFAOYSA-N [4-(2-aminoethyl)phenyl]sulfonylazanium;chloride Chemical compound [Cl-].NS(=O)(=O)C1=CC=C(CC[NH3+])C=C1 IAERAFZPWNQKDJ-UHFFFAOYSA-N 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、とくに少量の投与で血糖低下作用を
示すスルホニル尿素の製造に有用なカルボキシア
ミドエチルベンゼン−４−スルホンアミドの製造
方法に関するものである。一般式
（式中、Ｒは５−置換−イソキサゾール３−カ
ルボン酸残基でありかつR1は直鎖または分岐状
のC3以下のアルキル残基であるかまたはシクロ
アルキルである）で表される上記スルホニル尿素
は一般的にはカルボキシアミドエチルベンゼン−
４−スルホンアミド（）とアルキルイソシアネ
ート（）の反応、即ち次式：
（式中、ＲおよびR1は上記に定義したものと
同様である）によつて製造される。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing carboxyamidoethylbenzene-4-sulfonamide, which is useful for producing a sulfonylurea that exhibits a hypoglycemic effect particularly when administered in a small amount. . general formula (wherein R is a 5-substituted-isoxazole 3-carboxylic acid residue and R 1 is a linear or branched C 3 or less alkyl residue or cycloalkyl) Sulfonylureas are generally carboxyamidoethylbenzene-
The reaction between 4-sulfonamide () and alkyl isocyanate (), i.e., the following formula: (wherein R and R 1 are as defined above).
スルホニル尿素（）の工業的製造の収率およ
びコストは、必要な純度をもつ、対応するカルボ
キシアミドエチルベンゼン−４−スルホンアミド
（）の製造の収率およびコストに強く依存する。 The yield and cost of the industrial production of the sulfonylurea () strongly depends on the yield and cost of the production of the corresponding carboxyamidoethylbenzene-4-sulfonamide () with the required purity.
公知の技術にしたがつて、カルボキシアミドエ
チルベンゼン−４−スルホンアミド（）は酸Ｒ
−COOHの塩化物（）と４−（β−アミノエチ
ル）−ベンゼンスルホンアミド塩酸塩（）との
間の反応によつて調製される。 According to known techniques, carboxyamidoethylbenzene-4-sulfonamide () is prepared from the acid R
It is prepared by the reaction between the chloride of -COOH () and 4-(β-aminoethyl)-benzenesulfonamide hydrochloride ().
いずれにしても公知技術の一般的な教示によれ
ば、上記反応に必要な４−（β−アミノエチル）−
ベンゼンスルホンアミド（）は、βフエニルエ
チルアミン（）のスルホクロル化、アミド化お
よびかくして得られた中間体アミドの最終酸加水
分解によつて得られる。 In any case, according to the general teachings of the prior art, the 4-(β-aminoethyl)-
Benzenesulfonamide () is obtained by sulfochlorination of β-phenylethylamine (), amidation and final acid hydrolysis of the intermediate amide thus obtained.
β−フエニルエチルアミン（）のアミノ基が
上記反応に使用される前に、例えば無水酢酸によ
るβ−フエニルエチルアミン（）の処理（アセ
チル化）によつて、正確に保護されねばならない
ことを考慮すると、４−（β−アミノエチル）−ベ
ンゼンスルホンアミド（）、とくにその塩酸塩
の形での調製には、公知の技術の教示によれば、
以下の反応図式によつて理解できるような５つの
工程を必要とする。 Taking into account that the amino group of β-phenylethylamine () must be protected precisely before it is used in the above reaction, e.g. by treatment of β-phenylethylamine () with acetic anhydride (acetylation). For the preparation of 4-(β-aminoethyl)-benzenesulfonamide (), especially in the form of its hydrochloride, according to the teachings of the known art, then,
Five steps are required as can be understood by the reaction scheme below.
第６の工程、すなわち塩酸塩（）と適当な酸
RCOOHの塩化物（）の反応により、所望のカ
ルボキシアミドエチルベンゼン−４−スルホンア
ミド（）を得る。 Sixth step, i.e. hydrochloride () and suitable acid
Reaction of RCOOH with the chloride () gives the desired carboxamidoethylbenzene-4-sulfonamide ().
したがつて、この化合物（）の製造に、殊に
工業的観点からみれば個々の反応の部分的収率お
よび特別な中間生成物の高い純度の必要性にしば
られている限り必然的に劣つている。 Therefore, there are necessarily disadvantages in the preparation of this compound (), especially from an industrial point of view, which is bound by the need for partial yields of the individual reactions and high purity of the particular intermediate products. It's on.
本発明の基本的問題はそれゆえ、生成歩留りを
かなり良くしかつそれを得る費用、かつしたがつ
て得られるスルホニル尿素（）の生成歩留りお
よび費用を減少するように、カルボキシアミドエ
チルベンゼン−４−スルホンアミド（）の製造
に今までに必要とした反応の数を著しく減少させ
ることにある。 The basic problem of the present invention is therefore to obtain carboxyamidoethylbenzene-4-sulfonate in a manner that significantly improves the production yield and the cost of obtaining it, and thus reduces the production yield and cost of the sulfonylurea () obtained. The aim is to significantly reduce the number of reactions hitherto required for the production of amides ().
この問題は、本発明によれば、次の連続工程か
らなることを特徴とする方法によつて解決され
る。すなわち、
・β−フエニルエチルアミンを酸RCOOHの塩化
物（Ｒは５−置換−イソキサゾール３−カルボン
酸残基を示す。）と反応させ、式
（Ｒは上記と同じ意味を有する）
で表される中間生成物（）を得る、
・クロルスルホン酸による該中間生成物（）の
スルホクロル化
・濃アンモニアによるクロルスルホン化該中間生
成物のアミド化により、式
（式中、Ｒは上記で定義されたものに同じ）で
表されるカルボキシアミドエチルベンゼン−４−
スルホンアミドを得ること。 This problem is solved according to the invention by a method characterized in that it consists of the following successive steps. That is, by reacting β-phenylethylamine with the chloride of acid RCOOH (R represents a 5-substituted-isoxazole 3-carboxylic acid residue), the formula (R has the same meaning as above) Sulfochlorination of the intermediate product () with chlorosulfonic acid Chlorsulfonation with concentrated ammonia Amidation of the intermediate product According to the formula Carboxamidoethylbenzene-4- (wherein R is the same as defined above)
Obtaining the sulfonamide.
本発明方法の主たる利点は、公知技術の教示に
より現在まで必要な６つの段階に対して、単に３
つの段階でβ−フエニルエチルアミンから出発す
るカルボキシアミドエチルベンゼン−４−スルホ
ンアミド（）の製造が可能であることにある。
したがつて、結果として生ずるカルボキシアミド
エチルベンゼン−４−スルホンアミドおよびスル
ホニル尿素は現在まで可能であつたものに比して
著しく減少した費用で製造することができる。 The main advantage of the method according to the invention is that only 3 steps are needed, compared to the 6 steps required up to now according to the teachings of the prior art.
It is possible to prepare carboxyamidoethylbenzene-4-sulfonamide () starting from β-phenylethylamine in two steps.
The resulting carboxyamidoethylbenzene-4-sulfonamides and sulfonylureas can therefore be produced at significantly reduced costs compared to what has been possible to date.
留意すべきことは、本発明方法はβ−フエニル
エチルアミンと酸RCOOHの塩化物の直接反応に
より式
で表される上記中間生成物が得られることであ
り、それ故、この中間生成物が本発明の実質的な
特徴を構成するということである。 It should be noted that the process of the present invention involves the direct reaction of β-phenylethylamine with the chloride of acid RCOOH to form the formula Therefore, this intermediate product constitutes a substantial feature of the present invention.
本発明の方法によつて得られるカルボキシアミ
ドエチルベンゼン−４−スルホンアミド（）
は、古典的なすべての方法で、アルキルまたはシ
クロアルキルイソシアネート（）の適当量と反
応させることによつて、ほとんど定量的に相当す
るスルホニル尿素を得ることができる。 Carboxamidoethylbenzene-4-sulfonamide () obtained by the method of the present invention
can be obtained almost quantitatively to the corresponding sulfonylureas by reacting with appropriate amounts of alkyl or cycloalkyl isocyanates () by all classical methods.
本発明の好適な態様によれば、酸RCOOHの塩
化物は、β−フエニルエチルアミンとの反応によ
つて式
の中間生成物を与える５−メチルイソキサゾール
−３−カルボキシル酸塩化物よりなるものであ
る。 According to a preferred embodiment of the invention, the chloride of the acid RCOOH is prepared by reaction with β-phenylethylamine of the formula It consists of 5-methylisoxazole-3-carboxylic acid chloride giving the intermediate product.
そのような中間生成物をスルホクロル化および
アミド化することにより、一般式
に相当するカルボキシアミドエチルベンゼン−４
−スルホンアミドを得る。 By sulfochlorination and amidation of such intermediates, the general formula Carboxamidoethylbenzene-4 corresponding to
- Obtain the sulfonamide.
この生成物とシクロヘキシルイソシアネートと
の反応により、よく知られた式
に対応するグリソールアミドの名称で知られるス
ルホニル尿素を得る。 Reaction of this product with cyclohexyl isocyanate gives the well-known formula The corresponding sulfonylurea known under the name glycolamide is obtained.
以下に本発明の実施例を説明するが、これは本
発明の範囲をそれに限定するものではない。 Examples of the present invention will be described below, but the scope of the present invention is not limited thereto.
実施例 １
フラスコ内に一般的方法で調製された無水ピリ
ジン25ml中β−フエニルエチルアミン12.56ml
（0.1モル）溶液に、５−メチルイソキサゾール−
３−カルボニルクロリド14.5ｇ（0.1モル）を撹
拌しながらフラスコ内温度を０℃近くの値に制御
しながら滴下する。Example 1 12.56 ml of β-phenylethylamine in 25 ml of anhydrous pyridine prepared in a conventional manner in a flask.
(0.1 mol) solution, 5-methylisoxazole-
14.5 g (0.1 mol) of 3-carbonyl chloride is added dropwise while stirring while controlling the temperature inside the flask to a value close to 0°C.
滴下後、該溶液を室温で30分間撹拌し、次いで
70℃まで加熱する。この値に達した後、温度は２
時間で室温迄下がる。 After addition, the solution was stirred at room temperature for 30 minutes and then
Heat to 70℃. After reaching this value, the temperature is 2
It will drop to room temperature in time.
フラスコの内容物を氷水に注ぎ、沈澱物を減圧
脱水し、次いで洗浄する。40℃の恒温器での乾燥
後、式
のＮ−（β−フエニルエチル）−５−メチルイソキ
サゾール−３−カルボキシアミドからなる粗製中
間生成物23ｇ（収量100％）を得る。 The contents of the flask are poured into ice water and the precipitate is dried under reduced pressure and then washed. After drying in a thermostat at 40℃, the formula 23 g (100% yield) of a crude intermediate product consisting of N-(β-phenylethyl)-5-methylisoxazole-3-carboxamide are obtained.
イソプロピルエーテルで結晶化することによつ
て前記粗製生成物から出発して、理論値の約86％
の収量で中間体を得る。 Starting from the crude product by crystallization with isopropyl ether, approximately 86% of theory
The intermediate is obtained in a yield of .
この純粋な中間生成物は、水に不溶でかつ融点
89〜90℃のエタノールに可溶で、ほとんど不透明
な微晶質の白色物質である。 This pure intermediate product is insoluble in water and has a melting point of
It is a white, almost opaque, microcrystalline substance that is soluble in ethanol at 89-90°C.
シクロヘキサン−酢酸エチル（７：３）混合物
を展開液として使用してシリカゲル薄層クロマト
グラフイーにおいて、ただ１つのスポツトを認め
た。 Only one spot was observed in silica gel thin layer chromatography using a cyclohexane-ethyl acetate (7:3) mixture as the developing solution.
第２のフラスコ内で、無水クロロホルム15ml中
クロルスルホン酸3.015ml（0.044モル）の溶液を
調製し、そしてフラスコを−５℃に冷却した。こ
のクロルスルホン酸溶液に、フラスコ内の温度を
−５℃に制御しながら、無水クロロホルム20ml中
上述した純粋な中間生成物9.2ｇ（0.04モル）を
含む溶液を滴下する。この操作終了後、フラスコ
内の温度を室温まで上昇させ、更に30分後、水と
氷の混合物中にフラスコ内容物を注ぎ、温度が０
℃を越えないように保つ。 In a second flask, a solution of 3.015 ml (0.044 mol) of chlorosulfonic acid in 15 ml of anhydrous chloroform was prepared and the flask was cooled to -5°C. A solution containing 9.2 g (0.04 mol) of the pure intermediate product described above in 20 ml of anhydrous chloroform is added dropwise to this chlorosulfonic acid solution while controlling the temperature in the flask at -5°C. After completing this operation, the temperature inside the flask was raised to room temperature, and after another 30 minutes, the contents of the flask were poured into a mixture of water and ice until the temperature reached 0.
Keep the temperature below ℃.
次ぎに、クロロホルム層を分離し、無水硫酸ナ
トリウムで乾燥し、次いで真空下で溶媒を蒸発す
る。得られた残渣（12.5ｇ、収量92.5％）を室温
で、濃アンモニア水（28゜Be′）75mlで一夜撹拌す
る。 The chloroform layer is then separated, dried over anhydrous sodium sulfate, and then the solvent is evaporated under vacuum. The resulting residue (12.5 g, yield 92.5%) was stirred overnight at room temperature with 75 ml of concentrated aqueous ammonia (28° Be').
真空下で脱水して綿くず状沈澱を得、これを水
洗した後乾燥する。 Dehydration is performed under vacuum to obtain a fluff-like precipitate, which is washed with water and then dried.
この生成物を無水エタノール中で再結晶して式
に相当する４−〔β−（５−メチルイソキサゾリル
−３−カルボキシアミド）−エチル〕−ベンゼンス
ルホンアミド（融点219〜220℃）約10ｇを得る。 This product was recrystallized in absolute ethanol to give the formula Approximately 10 g of 4-[β-(5-methylisoxazolyl-3-carboxamido)-ethyl]-benzenesulfonamide (melting point 219 DEG -220 DEG C.) is obtained.
収量は理論値の約80％である。クロロホルム−
メタノール−酢酸（100：10.1）の展開液を使用
して、シリカゲル薄層クロマトグラフイーにおい
て、単一のスポツトを与えた。 The yield is about 80% of the theoretical value. Chloroform-
Single spots were generated in silica gel thin layer chromatography using methanol-acetic acid (100:10.1) eluent.
実施例 ２
フラスコ中に、β−フエニルエチルアミン
12.11ｇ（0.1モル）、ジメチルアニリン13.3ｇ
（0.11モル）および無水ベンゼン35mlの溶液を調
製する。こ溶液に５−メチルイソキサゾリル−３
−カルボニルクロリド14.5ｇ（0.1モル）を滴下
する。Example 2 In a flask, β-phenylethylamine
12.11g (0.1 mol), dimethylaniline 13.3g
(0.11 mol) and 35 ml of anhydrous benzene. Add 5-methylisoxazolyl-3 to this solution.
- 14.5 g (0.1 mol) of carbonyl chloride are added dropwise.
該溶液を70℃の急速加熱後、室温まで冷却す
る。フラスコ内容物を減圧濾過ベンゼン溶液を蒸
発乾固する。 The solution is rapidly heated to 70°C and then cooled to room temperature. The contents of the flask are filtered under reduced pressure and the benzene solution is evaporated to dryness.
残渣22.5ｇをエタノール中で再結晶してＮ−
（β−フエニルエチル）−５−メチルイソキサゾリ
ル−３−カルボキシアミド（融点89〜90℃）から
なる中間生成物19ｇ（理論値に対して収量82.5
％）を得る。 22.5 g of the residue was recrystallized in ethanol to give N-
19 g of intermediate product consisting of (β-phenylethyl)-5-methylisoxazolyl-3-carboxamide (melting point 89-90°C) (yield 82.5 based on theoretical value)
%).
中間生成物を実施例１記載と同様に処理して、
同じカルボキシアミドエチルベンゼン−４−スル
ホンアミド（）を得た。 The intermediate product was treated as described in Example 1,
The same carboxamidoethylbenzene-4-sulfonamide () was obtained.
本発明が例示として上述した好適な実施態様に
限定されず、かつ当業者が本発明の範囲および精
神から逸脱することなく種々の変形および種々の
変更をもたらすことができることが理解されよ
う。 It will be understood that the invention is not limited to the preferred embodiments described above by way of example, and that those skilled in the art can make various modifications and changes without departing from the scope and spirit of the invention.
Claims (1)
に有用なカルボキシアミドエチルベンゼン−４−
スルホンアミドの製法において、以下の工程、す
なわち、 (a) β−フエニルエチルアミンを酸
【式】の塩化物と反応させ て、 一般式 で表される中間生成物を得、 (b) クロルスルホン酸により該中間生成物（）
をスルホン化し、 (c) 前記中間生成物のスルホクロル化物を濃アン
モニアによりアミド化して、一般式 で表されるカルボキシアミドエチルベンゼン−
４−スルホンアミドを得る、 ことを含むことを特徴とするカルボキシアミドエ
チルベンゼン−４−スルホンアミドの製造方法。[Scope of Claims] 1. Carboxamidoethylbenzene-4- useful for producing sulfonylurea having hypoglycemic effect
In the method for producing sulfonamides, the following steps are carried out: (a) β-phenylethylamine is reacted with the chloride of the acid [formula] to form a compound of the general formula (b) converting the intermediate product ( ) with chlorosulfonic acid;
(c) The sulfochloride of the intermediate product is amidated with concentrated ammonia to obtain the general formula Carboxamidoethylbenzene represented by
A method for producing carboxyamidoethylbenzene-4-sulfonamide, comprising: obtaining 4-sulfonamide.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT7923578A IT1121577B (en) | 1979-06-14 | 1979-06-14 | PROCEDURE FOR THE PRODUCTION OF CARBOXAMIDE-ETHYLBENZEN-4-4SULPHONAMIDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55167278A JPS55167278A (en) | 1980-12-26 |
| JPH0215544B2 true JPH0215544B2 (en) | 1990-04-12 |
Family
ID=11208273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1018280A Granted JPS55167278A (en) | 1979-06-14 | 1980-02-01 | Manufacture of carboxyamidoethylbenzenee44sulfonamide |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS55167278A (en) |
| DE (1) | DE2950380A1 (en) |
| FR (1) | FR2459237A1 (en) |
| IT (1) | IT1121577B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4201047A1 (en) * | 1992-01-17 | 1993-07-22 | Bayer Ag | SUBSTITUTED ISOXAZOLE CARBONIC ACID AMIDES |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51136646A (en) * | 1975-04-18 | 1976-11-26 | Boehringer Mannheim Gmbh | Production of phenylalkane carboxylic acid and blood sugar and lipid lowering agent containing same |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH516578A (en) * | 1967-11-02 | 1971-12-15 | Bayer Ag | Process for the preparation of arylsulfonylureas containing heterocyclic acylamino groups and having an antihypertensive effect |
| DE1679952A1 (en) * | 1967-11-11 | 1971-06-09 | Basf Ag | Process for the production of molded articles from polyamides |
| US3965173A (en) * | 1971-05-21 | 1976-06-22 | Chubb Francis L | Process for preparing p-(5-chloro-2-methoxy-benzamidoethyl)-benzene sulfonamide |
-
1979
- 1979-06-14 IT IT7923578A patent/IT1121577B/en active
- 1979-12-10 FR FR7930249A patent/FR2459237A1/en active Granted
- 1979-12-14 DE DE19792950380 patent/DE2950380A1/en not_active Withdrawn
-
1980
- 1980-02-01 JP JP1018280A patent/JPS55167278A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51136646A (en) * | 1975-04-18 | 1976-11-26 | Boehringer Mannheim Gmbh | Production of phenylalkane carboxylic acid and blood sugar and lipid lowering agent containing same |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55167278A (en) | 1980-12-26 |
| IT7923578A0 (en) | 1979-06-14 |
| DE2950380A1 (en) | 1980-12-18 |
| FR2459237A1 (en) | 1981-01-09 |
| IT1121577B (en) | 1986-04-02 |
| FR2459237B1 (en) | 1983-10-14 |
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