JPH0442395B2 - - Google Patents
Info
- Publication number
- JPH0442395B2 JPH0442395B2 JP4641786A JP4641786A JPH0442395B2 JP H0442395 B2 JPH0442395 B2 JP H0442395B2 JP 4641786 A JP4641786 A JP 4641786A JP 4641786 A JP4641786 A JP 4641786A JP H0442395 B2 JPH0442395 B2 JP H0442395B2
- Authority
- JP
- Japan
- Prior art keywords
- thieno
- tetrahydro
- pyridine
- chloro
- benzyl
- 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012279 sodium borohydride Substances 0.000 claims description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 7
- ARHVQOBKFAPHQP-UHFFFAOYSA-N (2-chlorophenyl)-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)methanone Chemical compound ClC1=CC=CC=C1C(=O)N1CC(C=CS2)=C2CC1 ARHVQOBKFAPHQP-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- -1 lithium aluminum hydride Chemical compound 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 2
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-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
- ZHJTZFCCKYYGJK-UHFFFAOYSA-N 2-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound ClC1=CC=CC=C1CC(S1)=CC2=C1CCNC2 ZHJTZFCCKYYGJK-UHFFFAOYSA-N 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
- 125000000217 alkyl group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 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、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〕ピリジンの新規な製造方法に関する。本発明
の目的は、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を工業的に、かつ、高
収率で製造することにある。
（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
三つの方法がある。
(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合物と縮合させ、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、次いで、該
ピリジニウム塩を水素化して、前記の式（）
で示される化合物を得ることからなる。
(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て、次いで、ホルムアル
デヒドで還化して、前記の式（）で示される
化合物を得ることからなる。
(3) ヨーロピアン・ジヤーナル・オブ・メデイカ
ル・ケミストリー、−キミカ・テラペウテイカ
（Eur.J.Med.Chem.、−Chimca Therapeutica）
９、483（1974）に記載されている方法は、次式
（）
で示される化合物を水素化リチウムアルミニウ
ムで還元して、前記の式（）で示される化合
物を得ることからなる。
（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（）の公知の製造方法
の一例を挙げると、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、その後、還化し
て合成されるが、次式（）
で示されるジエチル−３−チエニリデンアミノア
セタールからの収率は、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。
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、これでも副生物の生成はさ
れられない。さらに、還化の段階においても、二
級アミンから三級アミンへの変換であり、分離精
製が非常に難しい。
(3)の方法では、還元剤として水素化リチウムア
ルミニウムを使用しており、、取り扱い上非常に
危険性があり、工業的実施プロセスとしては好ま
しくない。
（問題点を解決するための手段および作用）
本発明者は、上記の問題点を解決するため鋭意
検討した結果、次式（）
で示される５−（２−クロロ−ベンゾイル）−４，
５，６，７−テトラヒドロ−チエノ〔３，２−
Ｃ〕ピリジンを、酸性ジメチルスルホキシド中、
水素化ホウ素ナトリウムで還元することによる、
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〕ピリジンの製造方法を見い出した。
反応は、チエノピリジン誘導体（）と水素化
ホウ素ナトリウムを１対１〜10倍モル、望ましく
は１対１〜４倍モルの割合で溶解し、その溶液
に、酸性物質としてメタンスルホン酸、エタンス
ルホン酸、ベンゼンスルホン酸またはパラトルエ
ンスルホン酸を、チエノピリジン誘導体（）に
対して１〜15倍モル、望ましくは２〜５倍モルを
添加したDMSO溶液を0.5〜１時間で滴下し、滴
下終了後、50〜100℃で１〜３時間加熱して行わ
れる。目的物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〕ピリジンは塩基性物質であり、公知の精製操
作により容易に単離することができる。
（発明の効果）
本発明により、温和な還元剤である水素化ホウ
素ナトリウムを酸性DMSO中で使用することで、
取り扱い上危険である水素化リチウムアルミニウ
ムを使用せずに、アミド体であるチエノピリジン
誘導体を還元して、水素化リチウムアルミニウム
を用いた時と同じくらいの効率で、目的物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
することが可能となつた。さらに、中性物質から
塩基性物質へという、原料と生成物の関係がある
ため、分離精製が容易であり、工業的かつ経済的
実施プロセスである。
（実施例）
次に、本発明の実施例を挙げるが、この実施例
によつて本発明が限定されるものではない。
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
水素化ホウ素ナトリウム1.9ｇ（45ｍmol）と
５−（２−クロロ−ベンゾイル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジン
5.0ｇ（18ｍmol）を含むDMSO溶液30mlに、メ
タンスルホン酸3.8ml（63ｍmol）を含むDMSO
溶液30mlを30分で滴下し、70℃で２時間反応を行
つた。反応終了後、10％水酸化ナトリウム水溶液
50mlを添加し、エーテル50mlで３回抽出した。さ
らに、そのエーテル層を0.1N水酸化ナトリウム
30mlで３回洗浄し、DMSOを除去した。そのエ
ーテル層を10％塩酸50mlで３回抽出した。その水
層を10％水酸化ナトリウムでPH12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3.4ｇ（収率72％）を得た。
NMR、元素分析値を以下に示すが、これは目
的物の構造を支持する。
NMR （CDCl3）
δ（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 分析値
Ｃ 63.76％ 63.49％
Ｈ 5.31％ 5.47％
Ｎ 5.31％ 5.26％
Cl 13.47％ 13.17％
Ｓ 12.14％ 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
水素化ホウ素ナトリウム1.9ｇ（45ｍmol）と
５−（２−クロロ−ベンゾイル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジン
5.0ｇ（18ｍmol）を含むDMSO溶液30mlに、パ
ラトルエンスルホン酸10.8ｇ（63ｍmol）を含む
DMSO溶液30mlを30分で滴下し、70℃で２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2.8ｇ（収率59％）を得た。
NMR、元素分析値は、目的物の構造を支持す
る。
参考例 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
水素化リチウムアルミニウム0.95ｇ（25ｍ
mol）を含むエーテル50mlに、５−（２−クロロ
−ベンゾイル）−４，５，６，７−テトラヒドロ
−チエノ〔３，２−Ｃ〕ピリジン6.9ｇ（25ｍ
mol）を含むエーテル溶液30mlを滴下し、室温で
５時間反応させた。反応終了後、過剰の水素化リ
チウムアルミニウムを、水１〜２mlを滴下して不
活性化した。水酸化アルミ等の不溶物を別し、
液を10％塩酸50mlで３回抽出した。その水層を
10％水酸化ナトリウムでPH12とし、エーテル50ml
で３回抽出した。エーテル層を乾燥後、エーテル
を留去し、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5.1ｇ（収率77％）を得た。
NMR、元素分析値は、目的物の構造を支持す
る。
参考例 ２
水素化ホウ素ナトリウム1.9ｇ（45ｍmol）と
５−（２−クロロ−ベンゾイル）−４，５，６，７
−テトラヒドロ−チエノ〔３，２−Ｃ〕ピリジン
50ｇ（18ｍmol）を含むDMSO溶液40mlを、70℃
で２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つたが、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〕ピリジンは得られなかつた。 DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention provides 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Concerning a new method for producing pyridine. The object of the present invention is to provide 5-(2-chloro-benzyl)-4, which has an inhibitory effect on platelet aggregation and platelet adhesion.
5,6,7-tetrahydro-thieno[3,2-
C] To produce pyridine and its salts industrially and in high yield. (Prior art) 4,5,6,7-tetrahydro-thieno [3,
There are the following three methods for producing the 2-C]pyridine derivative. (1) The method described in Japanese Patent Publication No. 52-31357 uses the following formula () Thieno[3,2-C]pyridine represented by
The following formula () (In the formula, Hal represents a halogen atom.) By condensing with a halogen compound represented by the following formula () (In the formula, Hal has the same meaning as above.) A pyridinium salt represented by the above formula is obtained, and then the pyridinium salt is hydrogenated to form the formula ()
The process consists of obtaining a compound represented by (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 the formula (2) and then reducing the compound with formaldehyde to obtain a compound represented by the above formula (2). (3) European Journal of Medical Chemistry, -Chimca Therapeutica (Eur.J.Med.Chem., -Chimca Therapeutica)
9, 483 (1974), the following formula () The compound represented by formula (2) is reduced with lithium aluminum hydride to obtain the compound represented by formula (2). (Problems to be Solved by the Invention) However, in method (1), 3-thiophenaldehyde is It is synthesized by diethylaminoacetalization and then refluxation, and the following formula () The yield from diethyl-3-thienylidene aminoacetal is given by the Journal of the
American Chemical Society (J.Am.
According to Chem.Soc.) 75 , 5122 (1953), it is only 10%, and it cannot be called an economical and industrial implementation process. In addition, in method (2), by-products such as tertiary amines are produced in the reaction of 2-(2-thienyl)ethyl tosylate and 2-chlorobenzylamine, so purification and separation requires extremely complicated operations. is necessary. 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 even with this, no by-products are generated. Furthermore, in the reflux stage, secondary amines are converted to tertiary amines, which is extremely difficult to separate and purify. Method (3) uses lithium aluminum hydride as a reducing agent, which is extremely dangerous to handle and is not suitable for industrial implementation. (Means and effects for solving the problems) As a result of intensive studies to solve the above problems, the inventor found that the following formula () 5-(2-chloro-benzoyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Pyridine in acidic dimethyl sulfoxide,
By reduction with sodium borohydride,
The following formula () 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] A method for producing pyridine was discovered. The reaction is carried out by dissolving the thienopyridine derivative () and sodium borohydride in a ratio of 1 to 1 to 10 times the mole, preferably 1 to 1 to 4 times the mole, and adding methanesulfonic acid and ethanesulfonic acid as acidic substances to the solution. A DMSO solution containing benzenesulfonic acid or paratoluenesulfonic acid added in an amount of 1 to 15 times the mole, preferably 2 to 5 times the mole of the thienopyridine derivative (), is added dropwise over 0.5 to 1 hour. This is done by heating at ~100°C for 1 to 3 hours. Target product 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Pyridine is a basic substance and can be easily isolated by known purification procedures. (Effect of the invention) According to the present invention, by using sodium borohydride, which is a mild reducing agent, in acidic DMSO,
By reducing the amide thienopyridine derivative without using lithium aluminum hydride, which is dangerous to handle, the desired product 5- can be obtained with the same efficiency as when using lithium aluminum hydride.
It became possible to produce (2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine. Furthermore, because of the relationship between the raw materials and the products, from neutral substances to basic substances, separation and purification is easy, making it an industrial and economical process to implement. (Example) Next, examples of the present invention will be described, but the present invention is not limited to these examples. Example 1 5-(2-chloro-benzyl)-4,5,6,7
-Tetrahydro-thieno[3,2-C]pyridine Sodium borohydride 1.9 g (45 mmol) and 5-(2-chloro-benzoyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine
DMSO containing 3.8 ml (63 mmol) of methanesulfonic acid in 30 ml of DMSO solution containing 5.0 g (18 mmol)
30 ml of the solution was added dropwise over 30 minutes, and the reaction was carried out at 70°C for 2 hours. After the reaction is complete, add 10% aqueous sodium hydroxide solution.
50 ml was added and extracted three times with 50 ml of ether. Furthermore, the ether layer was diluted with 0.1N sodium hydroxide.
The DMSO was removed by washing three times with 30 ml. The ether layer was extracted three times with 50 ml of 10% hydrochloric acid. The aqueous layer was adjusted to pH 12 with 10% sodium hydroxide, and ether was added.
Extracted three times with 100 ml. After drying the ether layer, the ether was distilled off to give 5-(2-chloro-benzyl)
-4,5,6,7-tetrahydro-thieno[3,
3.4 g (yield 72%) of 2-C]pyridine was obtained. NMR and elemental analysis values are shown below, which support the structure of the target product. NMR (CDCl 3 ) δ (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 Analytical value C 63.76% 63.49% H 5.31% 5.47% N 5.31% 5.26% Cl 13.47% 13.17% S 12.14% 12.39% Example 2 5-(2-chloro-benzyl)-4,5,6,7
-Tetrahydro-thieno[3,2-C]pyridine Sodium borohydride 1.9 g (45 mmol) and 5-(2-chloro-benzoyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine
30 ml of DMSO solution containing 5.0 g (18 mmol) contains 10.8 g (63 mmol) of para-toluenesulfonic acid.
30 ml of DMSO solution was added dropwise over 30 minutes, and the mixture was reacted at 70°C for 2 hours. After the reaction was completed, the same post-treatment as in Example 1 was carried out to obtain 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] 2.8 g (yield 59%) of pyridine was obtained. NMR and elemental analysis values support the structure of the target product. Reference example 1 5-(2-chloro-benzyl)-4,5,6,7
-Tetrahydro-thieno[3,2-C]pyridine Lithium aluminum hydride 0.95g (25m
6.9 g of 5-(2-chloro-benzoyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine (25 mol)
30 ml of an ether solution containing mol) was added dropwise, and the mixture was allowed to react at room temperature for 5 hours. After the reaction was completed, excess lithium aluminum hydride was inactivated by dropwise addition of 1 to 2 ml of water. Separate insoluble materials such as aluminum hydroxide,
The liquid was extracted three times with 50 ml of 10% hydrochloric acid. that water layer
Adjust pH to 12 with 10% sodium hydroxide and 50ml of ether.
Extracted three times. After drying the ether layer, the ether was distilled off and 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] 5.1 g of pyridine (yield 77%) was obtained. NMR and elemental analysis values support the structure of the target product. Reference example 2 1.9 g (45 mmol) of sodium borohydride and 5-(2-chloro-benzoyl)-4,5,6,7
-tetrahydro-thieno[3,2-C]pyridine
40 ml of DMSO solution containing 50 g (18 mmol) was heated at 70°C.
The mixture was allowed to react for 2 hours. After the reaction was completed, the same post-treatment as in Example 1 was carried out, but 5-(2-chloro-
Benzyl)-4,5,6,7-tetrahydro-thieno[3,2-C]pyridine was not obtained.
Claims (1)
５，６，７−テトラヒドロ−チエノ〔３，２−
Ｃ〕ピリジンを、酸性ジメチルスルホキシド中、
水素化ホウ素ナトリウムで還元することを特徴と
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〕ピリジンの製造方法。 ２ 酸性ジメチルスルホキシドを調製するため
に、メタンスルホン酸、エタンスルホン酸、ベン
ゼンスルホン酸またはパラトルエンスルホン酸を
添加する特許請求の範囲第１項記載の製造方法。[Claims] Linear formula () 5-(2-chloro-benzoyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Pyridine in acidic dimethyl sulfoxide,
The following formula () characterized by reduction with sodium borohydride 5-(2-chloro-benzyl)-4,
5,6,7-tetrahydro-thieno[3,2-
C] Method for producing pyridine. 2. The manufacturing method according to claim 1, wherein methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or para-toluenesulfonic acid is added to prepare acidic dimethylsulfoxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4641786A JPS62205087A (en) | 1986-03-05 | 1986-03-05 | Production of ticlopidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4641786A JPS62205087A (en) | 1986-03-05 | 1986-03-05 | Production of ticlopidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62205087A JPS62205087A (en) | 1987-09-09 |
| JPH0442395B2 true JPH0442395B2 (en) | 1992-07-13 |
Family
ID=12746572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4641786A Granted JPS62205087A (en) | 1986-03-05 | 1986-03-05 | Production of ticlopidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62205087A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6043368A (en) * | 1996-09-04 | 2000-03-28 | Poli Industria Chimica, S.P.A. | Method of making thieno-pyridine derivatives |
-
1986
- 1986-03-05 JP JP4641786A patent/JPS62205087A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62205087A (en) | 1987-09-09 |
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