JPH0442394B2 - - Google Patents
Info
- Publication number
- JPH0442394B2 JPH0442394B2 JP11206385A JP11206385A JPH0442394B2 JP H0442394 B2 JPH0442394 B2 JP H0442394B2 JP 11206385 A JP11206385 A JP 11206385A JP 11206385 A JP11206385 A JP 11206385A JP H0442394 B2 JPH0442394 B2 JP H0442394B2
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- pyridine
- thieno
- benzyl
- tetrahydro
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- -1 2-chloro-benzyl-paratoluenesulfonate Chemical compound 0.000 claims description 8
- 150000003512 tertiary amines Chemical class 0.000 claims description 5
- OGUWOLDNYOTRBO-UHFFFAOYSA-N 4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1NCCC2=C1C=CS2 OGUWOLDNYOTRBO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 4
- BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WJFYLCXWEXZNHU-UHFFFAOYSA-N 2,3,3a,4-tetrahydrothieno[3,2-b]pyridine Chemical compound N1C=CC=C2SCCC21 WJFYLCXWEXZNHU-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PURSZYWBIQIANP-UHFFFAOYSA-N 1-(bromomethyl)-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CBr PURSZYWBIQIANP-UHFFFAOYSA-N 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- HLPRKWVEMYDPAU-UHFFFAOYSA-N 2-thiophen-2-ylethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC1=CC=CS1 HLPRKWVEMYDPAU-UHFFFAOYSA-N 0.000 description 1
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、血小板凝集および血小板粘着能の抑
制作用を有する５−（２−クロロ−ベンジル）−
４，５，６，７−テトラヒドロ−チエノ〔３，２
−Ｃ〕ピリジンおよびその塩の新規な製造方法に
関する。Detailed Description of the Invention (Industrial Field of Application) The present invention provides 5-(2-chloro-benzyl)-
4,5,6,7-tetrahydro-thieno[3,2
-C] A novel method for producing pyridine and its salts.
（従来の技術）
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジン誘導体の製造方法には、以下の
二つの方法がある。(Prior art) 4,5,6,7-tetrahydro-thieno [3,
There are the following two methods for producing the 2-C]pyridine derivative.
(1) 特公昭52−31357号公報に記載されている方
法は、次式（）
で示されるチエノ〔３，２−Ｃ〕ピリジンを次
式（）
（式中、Halはハロゲン原子を表わす。）
で示されるハロゲン化物と縮合させて、次式
（）
（式中、Halは前記と同じ意味を有する。）
で示されるピリジニウム塩を得て、ついで該ピ
リジニウム塩を水素化とし、前記式（）で示
される化合物を得ることからなる。(1) The method described in Japanese Patent Publication No. 52-31357 uses the following formula () The thieno[3,2-C]pyridine represented by the following formula () (In the formula, Hal represents a halogen atom.) By condensing with a halide represented by the following formula () (In the formula, Hal has the same meaning as above.) The process consists of obtaining a pyridinium salt represented by the following formula, and then hydrogenating the pyridinium salt to obtain a compound represented by the formula ().
(2) 特開昭51−101996号および特開昭54−1994号
公報に記載されている方法は、次式（）
（式中、R1は置換されたアルキル、アリール
またはアルキル基を表わす。）
で示される化合物を次式（）
で示されるアミンと縮合させ、次式（）
で示される化合物を得、ついでホルムアルデヒ
ドで環化して、前記式（）で示される化合物
を得ることからなる。(2) The method described in JP-A-51-101996 and JP-A-54-1994 is based on the following formula () (In the formula, R 1 represents a substituted alkyl, aryl or alkyl group.) A compound represented by the following formula () Condensation with the amine shown by the following formula () The method consists of obtaining a compound represented by formula (2) and then cyclizing with formaldehyde to obtain a compound represented by formula (2).
（発明が解決しようとする問題点）
しかし、(1)の方法では、原料となるチエノ
〔３，２−Ｃ〕ピリジン（）は、３−チオフエ
ンアルデヒドをジエチルアミノアセタール化し
て、次式（）
で示される化合物を得、その後環化して合成され
る。その環化の収率は、ジヤーナル・オブ・ザ・
アメリカン・ケミカル・ソサイアテイ（J.Am.
Chem.Soc.）75、5122（1953）によれば、10％に
すぎず、経済的かつ工業的実施プロセスとはいい
がたい。(Problems to be Solved by the Invention) However, in the method (1), the raw material thieno[3,2-C]pyridine () is obtained by converting 3-thiophenaldehyde into diethylaminoacetal and formulating the following formula (). The compound represented by is obtained and then cyclized to synthesize it. The yield of the cyclization is the Journal of the
American Chemical Society (J.Am.
According to Chem.Soc.) 75 , 5122 (1953), it is only 10% and cannot be called an economical and industrial implementation process.
また、(2)の方法では、２−（２−チエニル）−エ
チルトシレートと２−クロロ−ベンジルアミンと
の反応において、三級アミン等の副生物が多量に
生ずるため、精製分離に非常に煩雑な操作が必要
である。三級以上のアミン体の副生をさけようと
すると、該アミンをトシレートに対して、２倍モ
ル以上用いなければならず、該アミンからの収率
は低い。さらに、この方法でも副生物の生成はさ
けられない。 In addition, in method (2), a large amount of by-products such as tertiary amines are produced in the reaction of 2-(2-thienyl)-ethyl tosylate and 2-chloro-benzylamine, so it is extremely difficult to purify and separate. Requires complicated operations. In order to avoid the by-product of tertiary or higher class amines, the amine must be used in an amount of at least twice the mole of tosylate, and the yield from the amine is low. Furthermore, even with this method, the production of by-products cannot be avoided.
（問題点を解決するための手段および作用）
上記の問題点を解決するため鋭意検討した結
果、４，５，６，７−テトラヒドロ−チエノ
〔３，２−Ｃ〕ピリジンを２−クロロ−ベンジル
−パラトルエンスルホネートと反応させるかまた
は２−クロロ−ベンジルハライドと有機三級アミ
ンの存在下で反応させることにより、５−（２−
クロロ−ベンジル）−４，５，６，７−テトラヒ
ドロ−チエノ〔３，２−Ｃ〕ピリジンを高収率で
製造する方法を見い出した。(Means and effects for solving the problems) As a result of intensive studies to solve the above problems, we found that 4,5,6,7-tetrahydro-thieno[3,2-C]pyridine was replaced with 2-chloro-benzyl 5-(2-
We have found a method for producing chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine in high yield.
以下に、本発明の実施方法を詳しく説明する。 Below, the method of implementing the present invention will be explained in detail.
原料である４，５，６，７−テトラヒドロ−チ
エノ〔３，２−Ｃ〕ピリジンは、エス・グロンイ
ウイツ（S.Gronwitz）らの方法〔アルキブ・ホ
ー・ケミイ（ArK.Kemi.）32（19）、217、1970）
によつて容易に調製することができる。 The raw material 4,5,6,7-tetrahydro-thieno[3,2-C]pyridine was prepared by the method of S. Gronwitz et al. [ArK. Kemi. 32 (19 ), 217, 1970)
It can be easily prepared by
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジンに対して２−クロロ−ベンジル
−パラトルエンスルホネートまたは２−クロロ−
ベンジルハライドは、0.5〜２倍モル使用しても
よいが、望ましくは0.5〜１倍モルである。 4,5,6,7-tetrahydro-thieno[3,
2-C] 2-chloro-benzyl-paratoluenesulfonate or 2-chloro-
Benzyl halide may be used in an amount of 0.5 to 2 moles, preferably 0.5 to 1 mole.
反応温度は15〜100℃であり、望ましくは20〜
30℃である。 The reaction temperature is 15~100℃, preferably 20~
It is 30℃.
溶媒としては、アセトニトリル、エタノール、
メタノール、ベンゼン、トルエン、キシレン、
THF、ジオキサンなどであり、望ましくはアセ
トニル、ベンゼンである。 As a solvent, acetonitrile, ethanol,
methanol, benzene, toluene, xylene,
Examples include THF and dioxane, preferably acetonyl and benzene.
本反応において、２−クロロ−ベンジルハライ
ドを用いる場合は、触媒として有機三級アミンを
添加する。有機三級アミンとしては、トリエチル
アミン、ピリジン、トリエチレンジアミン、トリ
ブチルアミン、トリプロピルアミンなどであり、
望ましくはトリエチルアミン、ピリジンである。 In this reaction, when using 2-chloro-benzyl halide, an organic tertiary amine is added as a catalyst. Examples of organic tertiary amines include triethylamine, pyridine, triethylenediamine, tributylamine, tripropylamine, etc.
Preferred are triethylamine and pyridine.
有機三級アミンの添加量としては、テトラヒド
ロチエノピリジンに対して１〜10倍モル、望まし
くは１〜1.5倍モルである。 The amount of the organic tertiary amine added is 1 to 10 times, preferably 1 to 1.5 times, by mole relative to tetrahydrothienopyridine.
反応時間は１時間以上であり、望ましくは４〜
５時間である。 The reaction time is 1 hour or more, preferably 4 to 4 hours.
It is 5 hours.
試薬の添加方法は、同時に添加して反応を行つ
てもよいが、望ましくは２−クロロ−ベンジルハ
ライドあるいは２−クロロ−ベンジル−パラトル
エンスルホネートの溶液の中にテトラヒドロチエ
ノピリジンの溶液を徐々に添加する。反応終了後
は、抽出操作を行うだけで、容易に５−（２−ク
ロロ−ベンジル）−４，５，６，７−テトラヒド
ロ−チエノ〔３，２−Ｃ〕ピリジンを単離するこ
とができる。 The reagents may be added simultaneously to carry out the reaction, but preferably the solution of tetrahydrothienopyridine is gradually added to the solution of 2-chloro-benzyl halide or 2-chloro-benzyl-paratoluenesulfonate. . After the reaction is complete, 5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine can be easily isolated by simply performing an extraction operation. .
（発明の効果）
本発明により、高収率で、四級アミンなどの副
成の全くない高純度の５−（２−クロロ−ベンジ
ル）−４，５，６，７−テトラヒドロ−チエノ
〔３，２−Ｃ〕ピリジンを製造することができる。(Effects of the Invention) The present invention provides highly purified 5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3] with a high yield and no by-products such as quaternary amines. ,2-C]pyridine can be produced.
（実施例）
次に、本発明による実施例を以下に挙げるが、
この実施例によつて本発明が限定されるものでは
ない。(Example) Next, examples according to the present invention are listed below.
The present invention is not limited to this example.
実施例 １
５−（２−クロロ−ベンジル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジン10ｇ（72ｍmol）と２−クロロ
−ベンジルクロライド11.6ｇ（72ｍmol）および
トリエチルアミン11ml（79ｍmol）を、アセトニ
トリル100mlに溶解し、室温で４時間反応させた。
反応終了後、アセトニトリルを減圧留去し、この
反応混合物に水100ml、ジエチルエーテル100mlを
添加し、二層に分離後、水100mlで３回洗浄した。
エーテル層を2N−塩酸100mlで３回抽出し、その
水層を2N−水酸化ナトリウムでPH10とし、エー
テル100mlで３回抽出した。エーテル層を乾燥後、
エーテルを減圧留去して、５−（２−クロロ−ベ
ンジル）−４，５，６，７−テトラヒドロ−チエ
ノ〔３，２−Ｃ〕ピリジン16.4ｇ（モル収率：86
％）を得た。Example 1 5-(2-chloro-benzyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine 4,5,6,7-tetrahydro-thieno[3,
2-C] 10 g (72 mmol) of pyridine, 11.6 g (72 mmol) of 2-chloro-benzyl chloride, and 11 ml (79 mmol) of triethylamine were dissolved in 100 ml of acetonitrile, and reacted at room temperature for 4 hours.
After the reaction was completed, acetonitrile was distilled off under reduced pressure, and 100 ml of water and 100 ml of diethyl ether were added to the reaction mixture, which was separated into two layers and washed three times with 100 ml of water.
The ether layer was extracted three times with 100 ml of 2N hydrochloric acid, and the aqueous layer was adjusted to pH 10 with 2N sodium hydroxide and extracted three times with 100 ml of ether. After drying the ether layer,
The ether was distilled off under reduced pressure to give 16.4 g of 5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine (mole yield: 86
%) was obtained.
NMR、元素分析を以下に示すが、これは、目
的物の構造を支持する。 NMR, elemental analysis is shown below and supports the structure of the object.
NMR（機種）
（CDCl3）
δ値（ppm） 2.90（ｓ、4H）
3.60（ｓ、2H）
3.85（ｓ、2H）
6.90（dd、2H）
7.30（ｍ、4H）
元素分析
理論値 Ｃ 63.76％ Ｈ 5.31％ Ｎ 5.31％
Cl 13.47％ Ｓ 12.14％
分析値 Ｃ 63.49％ Ｈ 5.47％ Ｎ 5.26％
Cl 13.17％ Ｓ 12.39％
実施例 ２
５−（２−クロロ−ベンジル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジン10ｇ（72ｍmol）と２−クロロ
−ベンジルブロマイド14.8ｇ（72ｍmol）および
トリエチルアミン11ml（79ｍmol）を、ベンゼン
100mlに溶解し、室温で４時間反応させた。反応
終了後、実施例１と同様の処理を行い、５−（２
−クロロ−ベンジル）−４，５，６，７−テトラ
ヒドロ−チエノ〔３，２−Ｃ〕ピリジン17.2ｇ
（モル収率90）を得た。NMR、元素分析は、目
的物の構造を支持する。NMR (model) (CDCl 3 ) δ value (ppm) 2.90 (s, 4H) 3.60 (s, 2H) 3.85 (s, 2H) 6.90 (dd, 2H) 7.30 (m, 4H) Elemental analysis Theoretical value C 63.76% H 5.31% N 5.31% Cl 13.47% S 12.14% Analysis value C 63.49% H 5.47% N 5.26% Cl 13.17% S 12.39% Example 2 5-(2-chloro-benzyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine 4,5,6,7-tetrahydro-thieno[3,
2-C] 10 g (72 mmol) of pyridine, 14.8 g (72 mmol) of 2-chloro-benzyl bromide, and 11 ml (79 mmol) of triethylamine were added to benzene.
The mixture was dissolved in 100 ml and reacted at room temperature for 4 hours. After the reaction was completed, the same treatment as in Example 1 was carried out to obtain 5-(2
-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine 17.2g
(Molar yield 90) was obtained. NMR, elemental analysis supports the structure of the object.
実施例 ３
５−（２−クロロ−ベンジル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジン10ｇ（72ｍmol）と２−クロロ
−ベンジルクロライド11.6ｇ（72ｍmol）および
ピリジン6.4ml（79ｍmol）をアセトニトリル100
mlに溶解し、室温で４時間反応した。反応終了
後、実施例１と同様の処理を行い、５−（２−ク
ロロ−ベンジル）−４，５，６，７−テトラヒド
ロ−チエノ〔３，２−Ｃ〕ピリジン13.7ｇ（モル
収率72％）を得た。NMR、元素分析は、目的物
の構造を支持する。Example 3 5-(2-chloro-benzyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine 4,5,6,7-tetrahydro-thieno[3,
2-C] 10 g (72 mmol) of pyridine, 11.6 g (72 mmol) of 2-chloro-benzyl chloride, and 6.4 ml (79 mmol) of pyridine were dissolved in 100 g of acetonitrile.
ml and reacted at room temperature for 4 hours. After the reaction was completed, the same treatment as in Example 1 was carried out to obtain 13.7 g of 5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine (mole yield 72 %) was obtained. NMR, elemental analysis supports the structure of the object.
実施例 ４
５−（２−クロロ−ベンジル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン
４，５，６，７−テトラヒドロ−チエノ〔３，
２−Ｃ〕ピリジン10ｇ（72ｍmol）と２−クロロ
−ベンジルクロライド11.6ｇ（72ｍmol）を、ア
セトニトリル100mlに溶解し、室温で４時間反応
した。反応終了後、実施例１と同様の処理を行
い、５−（２−クロロ−ベンジル）−４，５，６，
７−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン4.6ｇ（モル収率24％）を得た。NMR、元素分
析は、目的物の構造を支持する。Example 4 5-(2-chloro-benzyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine 4,5,6,7-tetrahydro-thieno[3,
2-C] 10 g (72 mmol) of pyridine and 11.6 g (72 mmol) of 2-chloro-benzyl chloride were dissolved in 100 ml of acetonitrile and reacted at room temperature for 4 hours. After the reaction was completed, the same treatment as in Example 1 was carried out to obtain 5-(2-chloro-benzyl)-4,5,6,
4.6 g (24% molar yield) of 7-tetrahydro-thieno[3,2-C]pyridine was obtained. NMR, elemental analysis supports the structure of the object.
実施例 ５
５−（２−クロロ−ベンジル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジ
ン
２−クロロ−ベンジル−パラトルエンスルホネ
ート21.4ｇ（72ｍmol）をアセトニトリル70mlに
溶解後、アセトニトリル30mlに溶解した４，５，
６，７−テトラヒドロ−チエノ〔３，２−Ｃ〕ピ
リジンを徐々に添加して、室温で４時間反応させ
た。反応終了後は、実施例１と同様の後処理を行
ない、５−（２−クロロ−ベンジル）−４，５，
６，７−テトラヒドロ−チエノ〔３，２−Ｃ〕ピ
リジン15.1ｇ（モル収率79％）を得た。NMR、
元素分析は、目的物の構造を支持する。Example 5 5-(2-chloro-benzyl)-4,5,6,7
-Tetrahydro-thieno[3,2-C]pyridine 21.4 g (72 mmol) of 2-chloro-benzyl-paratoluenesulfonate was dissolved in 70 ml of acetonitrile, then 4,5,
6,7-tetrahydro-thieno[3,2-C]pyridine was slowly added and reacted for 4 hours at room temperature. After the reaction was completed, the same post-treatment as in Example 1 was carried out to obtain 5-(2-chloro-benzyl)-4,5,
15.1 g (79% molar yield) of 6,7-tetrahydro-thieno[3,2-C]pyridine was obtained. NMR,
Elemental analysis supports the structure of the object.
Claims (1)
ノ〔３，２−Ｃ〕ピリジンを２−クロロ−ベンジ
ル−パラトルエンスルホネートと反応させるかま
たは２−クロロ−ベンジルハライドと有機三級ア
ミンの存在下に反応させることを特徴とする次式
（） で示される５−（２−クロロ−ベンジル）−４，
５，６，７−テトラヒドロ−チエノ〔３，２−
Ｃ〕ピリジンおよびその塩の製造方法。[Claims] Linear formula () 4,5,6,7-tetrahydro-thieno[3,2-C]pyridine represented by reacting with 2-chloro-benzyl-paratoluenesulfonate or the presence of 2-chloro-benzyl halide and an organic tertiary amine. The following formula () characterized by reacting below 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Method for producing pyridine and its salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11206385A JPS61271291A (en) | 1985-05-27 | 1985-05-27 | Production of thienopyridine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11206385A JPS61271291A (en) | 1985-05-27 | 1985-05-27 | Production of thienopyridine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61271291A JPS61271291A (en) | 1986-12-01 |
| JPH0442394B2 true JPH0442394B2 (en) | 1992-07-13 |
Family
ID=14577116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11206385A Granted JPS61271291A (en) | 1985-05-27 | 1985-05-27 | Production of thienopyridine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61271291A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4906756A (en) * | 1988-05-10 | 1990-03-06 | Syntex (U.S.A.) Inc. | 2-(2-nitrovinyl)thiophene reduction and synthesis of thieno[3,2-c]pyridine derivatives |
-
1985
- 1985-05-27 JP JP11206385A patent/JPS61271291A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61271291A (en) | 1986-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7687631B2 (en) | Synthesis of diethyl{[5-(3-fluorophenyl)-pyridine-2yl]methyl}phosphonate | |
| JP2005501841A5 (en) | ||
| KR20090032009A (en) | New process for the synthesis of strontium ranelate and its hydrates | |
| JP3173602B2 (en) | Novel intermediate for the production of enyne derivatives and its production method | |
| KR970001157B1 (en) | Process and intermediates for preparing azabicyclo(2,2,2)octan-3-imines | |
| JPH0378395B2 (en) | ||
| JPH0442394B2 (en) | ||
| JP2668816B2 (en) | Process for producing benzothiadiazole derivative | |
| JP2007308510A (en) | Derivative of 2-aminobenzenesulfonic acid and 2-aminobenzenesulfonyl chloride, its production method, and its use as synthetic intermediate | |
| JPS62201842A (en) | Manufacture of 3-hydroxycyclopent-4-ene-1-ones | |
| NO147838B (en) | INTERMEDIATE FOR USE IN PREPARATION OF THE HYPOTENSIVE AGENT 2- (4- (2-FUROYL) PIPERAZIN-1-YL) -4-AMINO-6,7-DIMETOXYKINAZOLINE | |
| US6147226A (en) | Synthesis of cyclopentyl 2-thienyl ketone, tiletamine and tiletamine acid addition salts, such as tiletamine hydrochloride | |
| HU186944B (en) | Process for producing 2-oxo-5,6,7,7a-tetrahydro-4h-thieno-bracket-3,2-c-bracket closed-pyridine derivatives | |
| KR100203457B1 (en) | Process for terbinafine | |
| JP2767295B2 (en) | Method for producing indole-3-carbonitrile compound | |
| JPS607632B2 (en) | Method for producing thieno(3,2-C)pyridine and its derivatives | |
| JP2659587B2 (en) | 4-aziridinyl pyrimidine derivatives and their production | |
| JP2706554B2 (en) | 4-trifluoromethylaniline derivative and method for producing the same | |
| JP3252484B2 (en) | Method for producing 4,5-dihydro [1,2,4] triazolo [4,3-a] quinoxaline derivative | |
| JPH0442395B2 (en) | ||
| JP3903291B2 (en) | Process for producing 2,3,6,7,10,11-hexaalkoxytriphenylenes | |
| KR100619434B1 (en) | New manufacturing method of wine lab amide | |
| JP3650156B2 (en) | Process for producing trialkylsilyltrialkylsiloxymethylene compounds | |
| JP4018816B2 (en) | Cycloheptenone derivative and method for producing the same, and method for producing cycloheptimidazole derivative using the same | |
| JP2583791B2 (en) | Production method of halogenated ethylbenzene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |