JPS6041065B2 - Method for producing heterocyclic compounds - Google Patents
Method for producing heterocyclic compoundsInfo
- Publication number
- JPS6041065B2 JPS6041065B2 JP56081781A JP8178181A JPS6041065B2 JP S6041065 B2 JPS6041065 B2 JP S6041065B2 JP 56081781 A JP56081781 A JP 56081781A JP 8178181 A JP8178181 A JP 8178181A JP S6041065 B2 JPS6041065 B2 JP S6041065B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- formulas
- compound represented
- tables
- halogen
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 6
- 229910052736 halogen Chemical group 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- -1 alkali metal alkoxide Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000000739 antihistaminic agent Substances 0.000 description 6
- 229960001340 histamine Drugs 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229940125715 antihistaminic agent Drugs 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 102000000543 Histamine Receptors Human genes 0.000 description 3
- 108010002059 Histamine Receptors Proteins 0.000 description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 3
- 229960000582 mepyramine Drugs 0.000 description 3
- 125000005543 phthalimide group Chemical group 0.000 description 3
- CLEJZSNZYFJMKD-UHFFFAOYSA-N 3h-1,3-oxazole-2-thione Chemical compound SC1=NC=CO1 CLEJZSNZYFJMKD-UHFFFAOYSA-N 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N Glycolaldehyde Chemical compound OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- KGLPWQKSKUVKMJ-UHFFFAOYSA-N 2,3-dihydrophthalazine-1,4-dione Chemical compound C1=CC=C2C(=O)NNC(=O)C2=C1 KGLPWQKSKUVKMJ-UHFFFAOYSA-N 0.000 description 1
- NVIRBQTXAICWKC-UHFFFAOYSA-N 2-[3-(1,3-oxazol-2-ylsulfanyl)propyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCSC1=NC=CO1 NVIRBQTXAICWKC-UHFFFAOYSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- DRKPWFGAOIPYMS-UHFFFAOYSA-N 3-(1h-imidazol-2-ylsulfanyl)propan-1-amine;dihydrobromide Chemical compound Br.Br.NCCCSC1=NC=CN1 DRKPWFGAOIPYMS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QBOFLCYFXQBLPQ-UHFFFAOYSA-N 4-methyl-3h-1,3-oxazole-2-thione Chemical compound CC1=COC(S)=N1 QBOFLCYFXQBLPQ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102100021022 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 101100070541 Podospora anserina (strain S / ATCC MYA-4624 / DSM 980 / FGSC 10383) het-S gene Proteins 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- HDCXQTPVTAIPNZ-UHFFFAOYSA-N n-({[4-(aminosulfonyl)phenyl]amino}carbonyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NC1=CC=C(S(N)(=O)=O)C=C1 HDCXQTPVTAIPNZ-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
【発明の詳細な説明】
本発明は異項環式化合物の製造法、更に詳しくは、Ｈ−
１受容体以外のヒスタミン受容体に作用する抗ヒスタミ
ン剤として有用な化合物製造における中間体として有用
な異項環式化合物の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing heterocyclic compounds, more specifically, H-
The present invention relates to a method for producing a heterocyclic compound useful as an intermediate in the production of a compound useful as an antihistamine agent that acts on histamine receptors other than 1 receptor.
従来、生理学的活性物質はその活性を現わす過程におい
て、動物体内中、受容体として知られるある種の特殊な
役割を果たす部位と結合するものと仮定されている。Conventionally, it has been assumed that in the process of exerting its activity, physiologically active substances bind to sites in the animal body that play certain special roles, known as receptors.
ヒスタミンは動物体内において上記のごとき機作に従っ
て作用を発揮すると考えられている物質であって、その
作用には複数の種類があるところから、ヒスタミン受容
体にも複数の種類があるものと信じられている。通常、
抗ヒスタミン剤（たとえばメピラミン）と呼ばれる薬剤
によって阻止されるヒスタミン作用の類型は、アツシお
よびシールド‘こよりＨ−１と命名された受容体（ブリ
ティッシュ・ジャーナル・オブ・ファーマコロジー２７
巻４２７頁（１９６６年）参照）が関与するものと考え
られる。本発明の目的は、Ｈ−１受容体以外のヒスタミ
ン受容体に作用し、前記抗ヒスタミン剤によって抑制さ
れないある種のヒスタミン作用を抑制し、また、ガスト
リンの有するある種の作用に対する抑制剤として有用な
化合物製造における中間体として有用な異項環式化合物
の製造法を提供することである。Histamine is a substance that is thought to exert its effects in the animal body according to the mechanism described above, and since there are multiple types of its effects, it is believed that there are multiple types of histamine receptors as well. ing. usually,
The type of histamine action that is blocked by drugs called antihistamines (e.g., mepyramine) is based on a receptor named H-1 by Atsushi and Shields (British Journal of Pharmacology 27).
Vol. 427 (1966)) is thought to be involved. The object of the present invention is to provide a compound that acts on histamine receptors other than H-1 receptors, suppresses certain histamine effects that are not suppressed by the above-mentioned antihistamines, and is also useful as an inhibitor for certain effects of gastrin. An object of the present invention is to provide a method for producing a heterocyclic compound useful as an intermediate in production.
すなわち、本発明によれば、式
〔式中、Ｘ、１およびＡは後託と同意義〕で示される化
合物を式
Ｑ−（ＣＱ）ｍ−ＮＨ２
または
〔式中、ｍは後記と同意義。That is, according to the present invention, a compound represented by the formula [wherein, .
Ｑはヒドロキシまたはハロゲンを表す〕で示される化合
物と反応させ、フタルイミド保護基が存在する場合はこ
れを離脱させて、式〔式中、Ｘは水素、低級アルキルま
たはハロゲン、Ａは式中に示す炭素原子と合して形成さ
れる不飽和異項環基であって、チアゾリルまたはオキサ
ゾリル基を示す。Q represents hydroxy or halogen], and if a phthalimide protecting group is present, it is removed to form a compound of the formula [wherein X is hydrogen, lower alkyl or halogen, and A is shown in the formula] It is an unsaturated heterocyclic group formed by combining with a carbon atom, and represents a thiazolyl or oxazolyl group.
１は０または１、ｍは、１が０のとき３、１が１のとき
２を表す〕で示される目的とする異項環式化合物が得ら
れる。1 represents 0 or 1, m represents 3 when 1 is 0, and 2 when 1 represents 1] is obtained.
この反応は、該チオール出発物質に、たとえば、酸性条
件下アミノアルカノール、あるいはアルカリ性条件下ハ
ロアルキルアミンを反応させて行なえる。This reaction can be carried out by reacting the thiol starting material with, for example, an aminoalkanol under acidic conditions or a haloalkylamine under alkaline conditions.
また、フタルィミド保護基の離脱は、たとえば、反応終
了後に酸加水分解またはヒドラジノ分解することにより
行なえる。本発明で用いる出発物質は公知であるか、公
知の方法によって製造できる。Further, removal of the phthalimide protecting group can be carried out, for example, by acid hydrolysis or hydrazinolysis after completion of the reaction. The starting materials used in the present invention are known or can be prepared by known methods.
化合物〔１〕は酸付加塩の形で存在し得る。Compound [1] may exist in the form of an acid addition salt.
また、この酸付加塩を適当な塩基、たとえば、ナトリウ
ムェトキシドのごときアルカリ金属アルコキシドまたは
炭酸カリウムのごとき無機塩基と処理することによって
式〔１〕の遊離塩基を得ることができる。前記のごとく
、化合物〔１〕は動物体内においてメピラミンのごとき
抗ヒスタミン剤によって阻止されないある種のヒスタミ
ンの働きに対する措杭剤として有用な化合物の製造中間
体として用いられる。Alternatively, the free base of formula [1] can be obtained by treating this acid addition salt with a suitable base, for example an alkali metal alkoxide such as sodium ethoxide or an inorganic base such as potassium carbonate. As mentioned above, compound [1] is used as an intermediate in the production of a compound useful as a countermeasure against the effects of certain histamines that are not inhibited by antihistamines such as mepyramine in the animal body.
たとえば、式〔１〕の化合物を、式
Ｒ，一Ｎ＝Ｃ＝Ｅ
〔式中、Ｒ，は水素、低級アルキル、アシルまたはジァ
ルキルアミノアルキル、Ｅは酸素、硫黄またはＮＲ２を
示す。For example, the compound of formula [1] can be prepared by formula R, -N=C=E [wherein R represents hydrogen, lower alkyl, acyl or dialkylaminoalkyl, and E represents oxygen, sulfur or NR2].
Ｒ２は水素、ニトロまたはシアノを表わす〕で示される
化合物と反応させることによりメピラミンのごとき抗ヒ
スタミン剤によって阻止されないある種のヒスタミンの
働きに対する措抗剤として有用な化合物が得られる。R2 represents hydrogen, nitro, or cyano] to obtain a compound useful as an inhibitor against certain histamine effects that are not inhibited by antihistamines such as mepyramine.
つぎに参考例および実施例を挙げて本発明を更に詳しく
説明するが、これらに限定されるものではない。Next, the present invention will be explained in more detail with reference to Reference Examples and Examples, but the present invention is not limited thereto.
参考例 １
２−〆ルカプトイミダゾール２夕および３−アミノプロ
パノール１．１４泌の臭化水素酸溶液（４８％）２５肌
を２期時間加熱還流する。Reference Example 1 A hydrobromic acid solution (48%) containing 2 hours of 2-captoimidazole and 1.1 hours of 3-aminopropanol was heated under reflux for 2 hours.
反応混合物を蒸発、乾燥し、油状残留物から得られた固
形物をエタノールーェーテルから２回再結晶して、２一
（３−アミノプロピルメルカプト）イミダゾール・二臭
化水素酸塩３．５５夕を得る。融点：１６０〜１６ぞ○
。実施例 １
参考例１と同様にしてつぎの第１表に示す式Ｈｅｔ−Ｓ
−ＣＨ２Ｃ＆ＣＨ２ＮＨ２・２ＨＢｒで表わされる化合
物を得る。The reaction mixture was evaporated to dryness and the solid obtained from the oily residue was recrystallized twice from ethanol-ether to give 2-(3-aminopropylmercapto)imidazole dihydrobromide.3. Get 55 evenings. Melting point: 160~16○
. Example 1 Similarly to Reference Example 1, the formula Het-S shown in the following Table 1
A compound represented by -CH2C&CH2NH2.2HBr is obtained.
第１表には、該中間体から得られるヒスタミン桔抗剤と
して有用な最終生成物も合わせて示す。第１表
〔注）表中、＊＊＊は「Ｈｅｔ」の欄に示す異項環基を
意味する。Table 1 also shows the final products obtained from the intermediates which are useful as histamine antagonists. Table 1 [Note] In the table, *** means the heterocyclic group shown in the "Het" column.
実施例 ２
【ｉ｝ エタノール１８００必中カリウムチオシアネー
トに塩酸９０私を加え、無機物質を炉別して炉液にグリ
コールアルデヒド３５．９夕を加え、この溶液を２少時
間加熱還流する。Example 2 [i} 90% of hydrochloric acid is added to 1800% of potassium thiocyanate in ethanol, the inorganic substances are separated in a furnace, 35.9% of glycolaldehyde is added to the furnace liquid, and this solution is heated under reflux for 2 hours.
これを濃縮した後、冷やして白色固体を得、次いでエタ
ノールから再結晶してオキサゾール−２−チオール３０
夕を得る。融点：１４３〜１４４ｑ○。｛ｉｉ’ ３ー
フロモプロピルフタルイミド１３．４夕をナトリウムェ
トキシド（ナトリウム１．１５夕から得る。After concentrating and cooling, a white solid was obtained, which was then recrystallized from ethanol to obtain oxazole-2-thiol 30
Get the evening. Melting point: 143-144q○. {ii' 13.4 mm of 3-furomopropylphthalimide is obtained from 1.15 mm of sodium ethoxide.
）およびオキサゾールー２ーチオール５．１夕のエタノ
ールｌｏ０の‘溶液に燈拝しながら加える。この溶液を
２．５時間加熱還流し、減圧下に濃縮し、磯澄を水１０
０泌で処理して２一（３ーフタルイミドプロピルチオ）
オキサゾール１４夕を得る。融点：１０１ｏｏ。エタノ
ールから再結晶して純オキサゾール化合物を得る。融点
：１０２〜１０３ｑ○。価 ヒドラジンヒドレート５．
３夕を２−（３−フタルイミドプロピルチオ）オキサゾ
ール１０夕のエタノール１７３の‘溶液に縄拝しながら
注意して加え、この溶液を２５分間加熱還流する。) and oxazole-2-thiol 5.1 mL of ethanol solution. This solution was heated under reflux for 2.5 hours, concentrated under reduced pressure, and dissolved in 10 ml of water.
21 (3-phthalimidopropylthio) after treatment with 0 secretion
Obtain oxazole 14 days. Melting point: 101oo. Recrystallize from ethanol to obtain pure oxazole compound. Melting point: 102-103q○. Value Hydrazine hydrate 5.
Three parts of 2-(3-phthalimidopropylthio)oxazole are carefully added to a solution of ten parts of ethanol 173, and the solution is heated to reflux for 25 minutes.
冷後、フタルヒドラジドを炉則して、炉液を減圧下濃縮
し、残溝にエタノールを加えて再び蒸発させ、２一（３
−アミノプロピルチオ）オキサゾールを得る。実施例
３
実施例２の反応条件に準じて４−メチルオキサゾールー
２−チオール５．８夕を３−フロモプロピルフタルィミ
ド１３．４夕と反応させて、４ーメチル−２一（３−フ
タルイミドプロピルチオ）オキサゾール１４夕を得る。After cooling, the phthalhydrazide was concentrated under reduced pressure, and ethanol was added to the remaining groove and evaporated again.
-aminopropylthio)oxazole is obtained. Example
3 According to the reaction conditions of Example 2, 5.8 mm of 4-methyloxazole-2-thiol was reacted with 13.4 mm of 3-fluoropropylphthalimide to produce 4-methyl-2-(3-phthalimidopropyl). Thio)oxazole 14 is obtained.
エタノール−エーテルから結晶化後の融点：９２〜９３
℃。実施例２の反応条件に準じてこのフタルィミド化合
物からフタルィミド保護基を離脱させる。Melting point after crystallization from ethanol-ether: 92-93
℃. The phthalimide protecting group is removed from this phthalimide compound according to the reaction conditions of Example 2.
実施例 ４および５実施例１または実施例２と同機にし
てつぎの第２表に示す式Ｈｅｔ−ＣＨ２ＳＣＨ２ＣＨ２
ＮＨ２・２ＨＷ〔式中、Ｗは第２表に記載のピクレート
またはブロミドを意味する〕で示される化合物を得る。Examples 4 and 5 The same machine as Example 1 or 2 has the formula Het-CH2SCH2CH2 shown in Table 2 below.
A compound represented by NH2.2HW (wherein W means picrate or bromide listed in Table 2) is obtained.
なお、表中には該中間体から得られるヒスタミン措抗剤
として有用な最終生成物も合せて示す。第２表
実施例 ６
前記実施例１〜５と同様にしてつぎの化合物を得る。The table also shows the final product obtained from the intermediate, which is useful as a histamine inhibitor. Table 2 Example 6 The following compounds were obtained in the same manner as in Examples 1 to 5 above.
３一〔（２−アミノヱチル）チオメチル〕イソサゾール
臭化水素酸塩、融点１３１〜１３３℃４ープロモー３一
〔（２ーアミノエチル）チオメチル〕ィソチアゾール臭
化水素酸塩、融点１１１〜１１２０。3-[(2-aminoethyl)thiomethyl]isothiazole hydrobromide, melting point 131-133°C 4-promo 3-[(2-aminoethyl)thiomethyl]isothiazole hydrobromide, melting point 111-1120.
Claims (1)
化合物を式 Ｑ−（ＣＨ＿２）ｍ−ＮＨ＿２ 〔式中、ｍは後記と同意義。 Ｑはヒドロキシまたはハロゲンを表す〕で示される化合
物と反応させることを特徴とする式▲数式、化学式、表
等があります▼ 〔式中、Ｘは水素、低級アルキルまたはハロゲン、Ａ
は式中に示す炭素原子と合して形成される不飽和異項環
基であつて、チアゾリルまたはオキサゾリル基を示す。 ｌは０または１、ｍは、ｌが０のとき３、ｌが１のとき
２を表す〕で示される異項環式化合物の製造法。 ２ 式 ▲数式、化学式、表等があります▼ 〔式中、Ｘ、ｌおよびＡは後記と同意義〕で示される
化合物を式▲数式、化学式、表等があります▼ 〔式中、ｍは後記と同意義。 Ｑはヒドロキシまたはハロゲンを表す〕で示されるフタ
ルイミド保護化合物と反応させ、ついで該保護基を離脱
させることを特徴とする式▲数式、化学式、表等があり
ます▼ 〔式中、Ｘは水素、低級アルキルまたはハロゲ
ン、Ａは式中に示す炭素原子と合して形成される不飽和
異項環基であつて、チアゾリルまたはオキサゾリル基を
示す。 ｌは０または１、ｍは、ｌが０のとき３、ｌが１のとき
２を表す〕で示される異項環式化合物の製造法。[Claims] 1 A compound represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, X, l, and A have the same meanings as below] , m has the same meaning as below. There are formulas, chemical formulas, tables, etc. that are characterized by reacting with a compound represented by Q represents hydroxy or halogen.
represents an unsaturated heterocyclic group formed by combining with the carbon atoms shown in the formula, and represents a thiazolyl or oxazolyl group. l is 0 or 1; m is 3 when l is 0; and 2 when l is 1]. 2 A compound represented by the formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, Same meaning. There are formulas, chemical formulas, tables, etc. that are characterized by reacting with a phthalimide protected compound represented by Q represents hydroxy or halogen, and then removing the protecting group. Alkyl or halogen, A is an unsaturated heterocyclic group formed by combining with the carbon atom shown in the formula, and represents a thiazolyl or oxazolyl group. l is 0 or 1; m is 3 when l is 0; and 2 when l is 1].
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56081781A JPS6041065B2 (en) | 1981-05-27 | 1981-05-27 | Method for producing heterocyclic compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56081781A JPS6041065B2 (en) | 1981-05-27 | 1981-05-27 | Method for producing heterocyclic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57171976A JPS57171976A (en) | 1982-10-22 |
| JPS6041065B2 true JPS6041065B2 (en) | 1985-09-13 |
Family
ID=13756016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56081781A Expired JPS6041065B2 (en) | 1981-05-27 | 1981-05-27 | Method for producing heterocyclic compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6041065B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62143234U (en) * | 1986-03-04 | 1987-09-09 |
-
1981
- 1981-05-27 JP JP56081781A patent/JPS6041065B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62143234U (en) * | 1986-03-04 | 1987-09-09 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57171976A (en) | 1982-10-22 |
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