CA1088539A - Process for the preparation of 5-(2-chlorobenzyl)-4,5, 6,7-tetrahydrothieno ¬3,2-c| pyridine - Google Patents
Process for the preparation of 5-(2-chlorobenzyl)-4,5, 6,7-tetrahydrothieno ¬3,2-c| pyridineInfo
- Publication number
- CA1088539A CA1088539A CA295,721A CA295721A CA1088539A CA 1088539 A CA1088539 A CA 1088539A CA 295721 A CA295721 A CA 295721A CA 1088539 A CA1088539 A CA 1088539A
- Authority
- CA
- Canada
- Prior art keywords
- chlorobenzyl
- amine
- pyridine
- thienylethyl
- tetrahydrothieno
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Abstract
ABSTRACT OF THE DISCLOSURE
A process for the preparation of 5-(2-chlorobenzyl)-4,5,6 7-tetrahydrothien?[3,2-c]pyridine, wherein N-(2-thienylethyl)-N-hydroxymethyl-N-(2-chlorobenzyl) amine obtained from N-(2-thienylethyl)-N-(2-chlorobenzyl)amine and formaldehyde is submitted to cyclization.
A process for the preparation of 5-(2-chlorobenzyl)-4,5,6 7-tetrahydrothien?[3,2-c]pyridine, wherein N-(2-thienylethyl)-N-hydroxymethyl-N-(2-chlorobenzyl) amine obtained from N-(2-thienylethyl)-N-(2-chlorobenzyl)amine and formaldehyde is submitted to cyclization.
Description
Il 1~f~8539
- 2 -Subject of this in~ention i8 a new process for the preparation of 5-(2-chlorobenzyl)-4,5,6,7-tetrahydrothieno-¦ fi, 2- ~ pyridine, of the fo~mula (I) I /\, /=\
Q ~ ~2 ~ (I) This compound involves a great pharmacological and clinical interest due to it8 anti-inflammatory, ~asodilatatory and pla-telet aggregation inhibiting activity. See, to this purpose~
Eur.J.Med. Chem.-Chimica Therapeutica, September-October 1974, 9 , n5, pag. 487-490.
Compound (I) can be prepared in different ways either by reduction of 5-(2-chlorobenzyl)-thieno r,2-~ -pyridinium chloride (DOS 2404308)~ or by preliminary synthesis of the N-un~ub~tituted tetrahydro-4,5,6,7-thieno ~?-~ pyridine ring ~ollowed by the reaction with 2-chlorobenzyl chloride (Eur.J. ~ ; -~ed. Chem-Chimica ~herapeutica, September-October 1974, 9 , n5, pag. 483-486). Alte~natively, the latter paper also de-scribes the acylation of tetrahydro-4,5,6,7-thieno~3,?-c~-p~
ridine with 2-chlorobenzyl ahloride, and the following reduc- -tion of th8 CO to CH2 group by ~iAlH4.
None of the proce~s described is satisfactory in practise~
both be¢au6e of the poor yields and the cost of the reagents -used in the steps nece~sary for each synthetic pathway.
It has been fou~d now that compound (I) can be obtained in a completely sa~isfying way, eYen on an industrial scale, by cyclization of N-(2-thienylethyl)-N-(2-chlorobenzyl)-amine lV~8539 ¦(II) with formaldehyde, accordingly to the schema:
Cll2-C~I~-N~1-C~i2 ~ ~ (I) l (II) -¦ The ~tarting product of this reaction (which is characteriz d ¦with high yields) can be obtained in turn through two differen ¦ways of synthesi~, which offer no ~pecial di~ficulty.According ¦to the fir~t method, 2-chlorobenæylamine i~ acylated with 2-¦thienyl-acetic acid chloride~ and amide (III) 80 obtained is ¦reduced to amine (II~ by PC15 and NaBH4:
-COCl + H2N-CH2~ ~.
1) PC15 ¦ ~ ~ 2) NaBH
CH2-CO-NH-CH2 ~ ~ (II) Cl Alternatively a derivative of 2-thienylacetic acid (e.g.
either the ester according to the method of Bouveault-Blanc~
or the chloride with ~iAlH4, or the ester with NaBH4/ A1~13 too) can ~e reduced to 2-thienyl-ethanol. ~his latter compound is reaoted a9 the tosylate~ directly affording the amine (II) together with 2-chlorobenzylamine 1 10~8539 1) To~ylchloride ¦ ~ 2~ 2-chlorobenzylamine ¦ ~ ~ CH2-CH20H ~ (II3 The reaction of the amine (II), whenever obtained~ with formaldehyde, in the pre~ence of anhydrou~ HCl, preferably in ~.
dimethylformamide solution~ yields the final product (I) withou~ difficulty It i~ not necessary to isolate the N-hydro~ymethyl intermediate, the product from cyclization being directly reached :
_ ,~
HCH0 CH2H HCl (I
L~S~--CH2 aH2 ~ C 12 (III) , ' , " ' ~he invention i9 illuetrated by the following example~
which are not intended ae a limitation thereof. : ;
E~A}1~E 1 . ,.
~:: ~:
a) N-(2-thien~la¢etyl)-N-(2-chlorobenzyl)amine - ..
o-ehlorobenzylamine (141 g) and triethylamine (101 g) were dis~olved in 600 ml of anhydrou~ benzene. ~nder ~tirring, 160 : ~g o~ 2-thienylacetic acid chloride were~ adde~, the temperature .
. ~ being mantained at 35-40C. A precipitate developed immediatel~ .
After comFletion of the addition the ~olution wae heated for ~ -~,: :, `67 ~
:~ . ' ;.. . . , . ~
30' to 60-65C, the precipitate dissolving again. After cooling, 1 liter of CH2C12 was added and the mixture washed with S00 ml of H2O. The organic layer was dried on MgSO4, then filtered and concentrated to approx. 500 ml "in vacuo". After dllution with 400 ml of n-pentane, the reaction was left for one hour at 0, and the crystalline product was subsequently filtered: yield 200 g, m.p. 104-105C. The analytical data agreed with the values calculated; the compound was shown to be unitary by thin-layer chromatography.
b) N-~2-thienylethyl)-N-(2-chlorobenxyl)amine ~ ~ `~
106 g (0.4 mole) of the amide as previously described, dissolved in 500 ml of CHC13, were treated wlth 104 g (0.5 mole) of PC15 and refluxed for 5'. The mixture was cooled to QC, 46 g (1.2 mole) of NaBH4, suspended in 500 ml of absolute ethanol, were added during 15' with stirring, keeping the temperature between 0C and 5C. After heating to 60 for 10' and cooling to 0-5C a solution of 100 g of Na2CO3 in a liter of water was slowly added under stirring and external cooling with an ice bath. The reacting mixture was repeatedly extracted with CH2C12 and the combined extracts were evaporated. The residue was taken up with 300 ml of conc. HCl and 300 ml of water, then 300 ml of diisopropyl ether were added and the mixture stirred for 10'.
~ he crystalline precipitate (the amine hydrochloride) was suspended in water and treated with excess Na2CO3; the free base was extracted with diisopropyl ether and distilled "in 10~8539 vacuo". B.~.o 3 135-140C. 74 g of the product, unitary by thin ¦layer chromatography, were obtained.
¦The ~nalytical and ~pectro~copic data were in ag~eement with ¦the expected structure.
c) N-(2-thienylethyl)-N-(2-chlorobenzyl)-N-hydroxvmethyl-amine.
18.3 g of N-(2-thienylethyl)-N-chlorobenzylamine were dissolved ¦in 100 ml of toluene and 10 ml o~ 40~0 HCH0 were added to the ¦solution. After ~tirring for 5'~ the organic pha~e was sepa-¦rated and dried on MgS04; the solvent was removed and the /0 ¦residue distilled "in vacuo"0 The yield of the N-hydroxymethyl ¦derivative, b.p.o 1 1~5-165a, was 6.7 g.
¦d) 5-(2-chlorobenzyl)-4~5~6~7-tetrahydrothie ~ ,2-~ -pyridine .
5 g of N-(2-thienylmethyl)-N-(2-chlorobenzyl)-N-hydroxy-methyl amine were dissolved in 10 ml of a 5N HCl solution in anhydrou~ dimethylformamide. After standing at room temperatur~
o~ernight~ the reacting mixture was ¢ooled to -5C. The crysta~
line precipitate was filtered at the pump~ then washed with I anhydrous acetone and dr~ed: 4.3 g of 5-(2-chlorobenzyl)-4~5~6 ¦ 7-tetrahydrothieno~ ~2-~ pyridine hydrochloride, m.p. 201-203 0 C~ were obtained.
~ he analytical and spectroscopic data were in perfect agree-ment with the compound ~tructure, which was found unitary~by ~thin-layer chromatography.
EXAMP~E 2 a) N-(2-thienylethyl)-N-(2-chlorobenzyl)amine In a round bottomed flask, fitted with a ~tirrer~ a ther-mometer~ a dropping funnel and a reflux condenser, 6 g of a ~7 78~ solution of ~odium hydride in paraffin oil and 100 ml of ~, . . .
~0~8539 ¦ anhydrous tetrahydrofuu~dn were added under anhydrous nitrogen l Then 24 g of 2-thienylethanol (produced by reducing ethyl ¦ 2-thienylacetate with ~aBH4/AlC13) dissolved in 30 ml of ¦ tetrahydrofuran were quickly added. The mixture obtained was ¦ heated to 50C ~der ~tirring, until a clear solution was ¦ obtained. This solution was cooled to -2C and 33.2 g of ¦ 4-toluene-sulphonyl chloride in 50 ml of anhydrous tetrahy-¦ furan were dropned over approx. 30'. At the end of the additic n ¦ the cooling bath wa~ removed and a solution of 50 g of ¦ 2-chlorobenzylamine in 50 ml of tetrahydrofuran was dropped.
l ~he mixture was then heated to 70C and kept`at this tempe~
¦ ature for 10'. By cooling to 10C~ 20g of 2-chlorobenzylamine ¦ toluensulphonate precipitated~ which were recovered by ¦ filtration "in vacuo". ~he filtrate was evaporated at reduced ¦ pressure~ taken up with 140 ml of water Qnd basified with ¦ Na2C03 and the base was extracted with CH2C12. ~he solution in CH2C12was dried on E2C03 and evaporated to dryness. By ¦ distilling the re~idue "in vacuo" the a~ine~ identical to that I prepared according to example 1b)~ was obtained in a yield of c2~ 1 33 g~
l b~ 5-(2-chlorobenzyl)-4~5~6~7-tetrahydrothieno 6~2- ~ pyridine ~; I .................................................................... .,-17.5 g of N-~2-thienylethyl)-N-(2-chlorobenzyl~a-nine~
dissolved in 65 ml of toluene~ were treated with 20 ml o~ 40 aqueous CH20. A~ter stirring for 10' at room temperature the aqueous layer was separated and discarded and the toluene laye ~, -~088539 was dried on Na2S04. This solution was treated with 22.5 ml of a 5N HCl solutionin dimethylformamide, and processed as in example ld); 15 g of product ~I), pure on the basis of thin-layer chromatography, were obtained.
Q ~ ~2 ~ (I) This compound involves a great pharmacological and clinical interest due to it8 anti-inflammatory, ~asodilatatory and pla-telet aggregation inhibiting activity. See, to this purpose~
Eur.J.Med. Chem.-Chimica Therapeutica, September-October 1974, 9 , n5, pag. 487-490.
Compound (I) can be prepared in different ways either by reduction of 5-(2-chlorobenzyl)-thieno r,2-~ -pyridinium chloride (DOS 2404308)~ or by preliminary synthesis of the N-un~ub~tituted tetrahydro-4,5,6,7-thieno ~?-~ pyridine ring ~ollowed by the reaction with 2-chlorobenzyl chloride (Eur.J. ~ ; -~ed. Chem-Chimica ~herapeutica, September-October 1974, 9 , n5, pag. 483-486). Alte~natively, the latter paper also de-scribes the acylation of tetrahydro-4,5,6,7-thieno~3,?-c~-p~
ridine with 2-chlorobenzyl ahloride, and the following reduc- -tion of th8 CO to CH2 group by ~iAlH4.
None of the proce~s described is satisfactory in practise~
both be¢au6e of the poor yields and the cost of the reagents -used in the steps nece~sary for each synthetic pathway.
It has been fou~d now that compound (I) can be obtained in a completely sa~isfying way, eYen on an industrial scale, by cyclization of N-(2-thienylethyl)-N-(2-chlorobenzyl)-amine lV~8539 ¦(II) with formaldehyde, accordingly to the schema:
Cll2-C~I~-N~1-C~i2 ~ ~ (I) l (II) -¦ The ~tarting product of this reaction (which is characteriz d ¦with high yields) can be obtained in turn through two differen ¦ways of synthesi~, which offer no ~pecial di~ficulty.According ¦to the fir~t method, 2-chlorobenæylamine i~ acylated with 2-¦thienyl-acetic acid chloride~ and amide (III) 80 obtained is ¦reduced to amine (II~ by PC15 and NaBH4:
-COCl + H2N-CH2~ ~.
1) PC15 ¦ ~ ~ 2) NaBH
CH2-CO-NH-CH2 ~ ~ (II) Cl Alternatively a derivative of 2-thienylacetic acid (e.g.
either the ester according to the method of Bouveault-Blanc~
or the chloride with ~iAlH4, or the ester with NaBH4/ A1~13 too) can ~e reduced to 2-thienyl-ethanol. ~his latter compound is reaoted a9 the tosylate~ directly affording the amine (II) together with 2-chlorobenzylamine 1 10~8539 1) To~ylchloride ¦ ~ 2~ 2-chlorobenzylamine ¦ ~ ~ CH2-CH20H ~ (II3 The reaction of the amine (II), whenever obtained~ with formaldehyde, in the pre~ence of anhydrou~ HCl, preferably in ~.
dimethylformamide solution~ yields the final product (I) withou~ difficulty It i~ not necessary to isolate the N-hydro~ymethyl intermediate, the product from cyclization being directly reached :
_ ,~
HCH0 CH2H HCl (I
L~S~--CH2 aH2 ~ C 12 (III) , ' , " ' ~he invention i9 illuetrated by the following example~
which are not intended ae a limitation thereof. : ;
E~A}1~E 1 . ,.
~:: ~:
a) N-(2-thien~la¢etyl)-N-(2-chlorobenzyl)amine - ..
o-ehlorobenzylamine (141 g) and triethylamine (101 g) were dis~olved in 600 ml of anhydrou~ benzene. ~nder ~tirring, 160 : ~g o~ 2-thienylacetic acid chloride were~ adde~, the temperature .
. ~ being mantained at 35-40C. A precipitate developed immediatel~ .
After comFletion of the addition the ~olution wae heated for ~ -~,: :, `67 ~
:~ . ' ;.. . . , . ~
30' to 60-65C, the precipitate dissolving again. After cooling, 1 liter of CH2C12 was added and the mixture washed with S00 ml of H2O. The organic layer was dried on MgSO4, then filtered and concentrated to approx. 500 ml "in vacuo". After dllution with 400 ml of n-pentane, the reaction was left for one hour at 0, and the crystalline product was subsequently filtered: yield 200 g, m.p. 104-105C. The analytical data agreed with the values calculated; the compound was shown to be unitary by thin-layer chromatography.
b) N-~2-thienylethyl)-N-(2-chlorobenxyl)amine ~ ~ `~
106 g (0.4 mole) of the amide as previously described, dissolved in 500 ml of CHC13, were treated wlth 104 g (0.5 mole) of PC15 and refluxed for 5'. The mixture was cooled to QC, 46 g (1.2 mole) of NaBH4, suspended in 500 ml of absolute ethanol, were added during 15' with stirring, keeping the temperature between 0C and 5C. After heating to 60 for 10' and cooling to 0-5C a solution of 100 g of Na2CO3 in a liter of water was slowly added under stirring and external cooling with an ice bath. The reacting mixture was repeatedly extracted with CH2C12 and the combined extracts were evaporated. The residue was taken up with 300 ml of conc. HCl and 300 ml of water, then 300 ml of diisopropyl ether were added and the mixture stirred for 10'.
~ he crystalline precipitate (the amine hydrochloride) was suspended in water and treated with excess Na2CO3; the free base was extracted with diisopropyl ether and distilled "in 10~8539 vacuo". B.~.o 3 135-140C. 74 g of the product, unitary by thin ¦layer chromatography, were obtained.
¦The ~nalytical and ~pectro~copic data were in ag~eement with ¦the expected structure.
c) N-(2-thienylethyl)-N-(2-chlorobenzyl)-N-hydroxvmethyl-amine.
18.3 g of N-(2-thienylethyl)-N-chlorobenzylamine were dissolved ¦in 100 ml of toluene and 10 ml o~ 40~0 HCH0 were added to the ¦solution. After ~tirring for 5'~ the organic pha~e was sepa-¦rated and dried on MgS04; the solvent was removed and the /0 ¦residue distilled "in vacuo"0 The yield of the N-hydroxymethyl ¦derivative, b.p.o 1 1~5-165a, was 6.7 g.
¦d) 5-(2-chlorobenzyl)-4~5~6~7-tetrahydrothie ~ ,2-~ -pyridine .
5 g of N-(2-thienylmethyl)-N-(2-chlorobenzyl)-N-hydroxy-methyl amine were dissolved in 10 ml of a 5N HCl solution in anhydrou~ dimethylformamide. After standing at room temperatur~
o~ernight~ the reacting mixture was ¢ooled to -5C. The crysta~
line precipitate was filtered at the pump~ then washed with I anhydrous acetone and dr~ed: 4.3 g of 5-(2-chlorobenzyl)-4~5~6 ¦ 7-tetrahydrothieno~ ~2-~ pyridine hydrochloride, m.p. 201-203 0 C~ were obtained.
~ he analytical and spectroscopic data were in perfect agree-ment with the compound ~tructure, which was found unitary~by ~thin-layer chromatography.
EXAMP~E 2 a) N-(2-thienylethyl)-N-(2-chlorobenzyl)amine In a round bottomed flask, fitted with a ~tirrer~ a ther-mometer~ a dropping funnel and a reflux condenser, 6 g of a ~7 78~ solution of ~odium hydride in paraffin oil and 100 ml of ~, . . .
~0~8539 ¦ anhydrous tetrahydrofuu~dn were added under anhydrous nitrogen l Then 24 g of 2-thienylethanol (produced by reducing ethyl ¦ 2-thienylacetate with ~aBH4/AlC13) dissolved in 30 ml of ¦ tetrahydrofuran were quickly added. The mixture obtained was ¦ heated to 50C ~der ~tirring, until a clear solution was ¦ obtained. This solution was cooled to -2C and 33.2 g of ¦ 4-toluene-sulphonyl chloride in 50 ml of anhydrous tetrahy-¦ furan were dropned over approx. 30'. At the end of the additic n ¦ the cooling bath wa~ removed and a solution of 50 g of ¦ 2-chlorobenzylamine in 50 ml of tetrahydrofuran was dropped.
l ~he mixture was then heated to 70C and kept`at this tempe~
¦ ature for 10'. By cooling to 10C~ 20g of 2-chlorobenzylamine ¦ toluensulphonate precipitated~ which were recovered by ¦ filtration "in vacuo". ~he filtrate was evaporated at reduced ¦ pressure~ taken up with 140 ml of water Qnd basified with ¦ Na2C03 and the base was extracted with CH2C12. ~he solution in CH2C12was dried on E2C03 and evaporated to dryness. By ¦ distilling the re~idue "in vacuo" the a~ine~ identical to that I prepared according to example 1b)~ was obtained in a yield of c2~ 1 33 g~
l b~ 5-(2-chlorobenzyl)-4~5~6~7-tetrahydrothieno 6~2- ~ pyridine ~; I .................................................................... .,-17.5 g of N-~2-thienylethyl)-N-(2-chlorobenzyl~a-nine~
dissolved in 65 ml of toluene~ were treated with 20 ml o~ 40 aqueous CH20. A~ter stirring for 10' at room temperature the aqueous layer was separated and discarded and the toluene laye ~, -~088539 was dried on Na2S04. This solution was treated with 22.5 ml of a 5N HCl solutionin dimethylformamide, and processed as in example ld); 15 g of product ~I), pure on the basis of thin-layer chromatography, were obtained.
Claims (4)
1. A process for the preparation of 5-(2-chlorobenxyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridine, wherein N-(2-thienyl-ethyl)-N-hydroxymethyl-N-(2-chlorobenxyl) amine obtained from N-(2-thienylethyl)-N-(2-chlorobenzyl) amine and formaldehyde is submitted to cyclizatlon.
2. A process as claimed in claim 1, wherein the cyclization is carried out with anhydrous HCl in an anhydrous solvent.
3. A process as claimed in claim 2, wherein the solvent used is dimethylformamide.
4. A process as claimed in claims 1-3, wherein the cyclization is carried out directly on the reaction product of N-(2-thienylethyl)-N-(2-chlorobenzyl) amine with formal-dehyde, extracted from the aqueous phase.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT41002/77A IT1082336B (en) | 1977-01-27 | 1977-01-27 | PROCESS FOR THE PREPARATION OF 5.2.CLOROBENZIL. 4 5 6 7.TETRAIDRO TIEN 3 2.C. PYRIDINE |
| IT41.002A.77 | 1977-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1088539A true CA1088539A (en) | 1980-10-28 |
Family
ID=11249989
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA295,721A Expired CA1088539A (en) | 1977-01-27 | 1978-01-26 | Process for the preparation of 5-(2-chlorobenzyl)-4,5, 6,7-tetrahydrothieno ¬3,2-c| pyridine |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS5395994A (en) |
| CA (1) | CA1088539A (en) |
| GR (1) | GR63080B (en) |
| IT (1) | IT1082336B (en) |
| NL (1) | NL7801004A (en) |
| SE (1) | SE7800990L (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2508453A1 (en) * | 1981-06-30 | 1982-12-31 | Sanofi Sa | PROCESS FOR THE PREPARATION OF (THIENYL-2) AND THIENYL-3) -2-ETHYLAMINE DERIVATIVES AND PRODUCTS THUS OBTAINED |
| EP0068979A1 (en) * | 1981-06-30 | 1983-01-05 | Elf Sanofi | Process for the preparation of (thienyl-2) and (thienyl-3)-2 ethyl amine derivatives, and products so obtained |
| CN105601644A (en) * | 2015-12-31 | 2016-05-25 | 苏州弘森药业有限公司 | Novel method for synthesizing ticlopidine hydrochloride |
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 |
-
1977
- 1977-01-27 IT IT41002/77A patent/IT1082336B/en active
-
1978
- 1978-01-26 SE SE7800990A patent/SE7800990L/en unknown
- 1978-01-26 JP JP817978A patent/JPS5395994A/en active Pending
- 1978-01-26 CA CA295,721A patent/CA1088539A/en not_active Expired
- 1978-01-27 NL NL7801004A patent/NL7801004A/en not_active Application Discontinuation
- 1978-01-27 GR GR55293A patent/GR63080B/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2508453A1 (en) * | 1981-06-30 | 1982-12-31 | Sanofi Sa | PROCESS FOR THE PREPARATION OF (THIENYL-2) AND THIENYL-3) -2-ETHYLAMINE DERIVATIVES AND PRODUCTS THUS OBTAINED |
| EP0068979A1 (en) * | 1981-06-30 | 1983-01-05 | Elf Sanofi | Process for the preparation of (thienyl-2) and (thienyl-3)-2 ethyl amine derivatives, and products so obtained |
| EP0068978A1 (en) * | 1981-06-30 | 1983-01-05 | Elf Sanofi | Process for the preparation of (thienyl-2)- and (thienyl-3)-2 ethylamine derivatives, and products so obtained |
| CN105601644A (en) * | 2015-12-31 | 2016-05-25 | 苏州弘森药业有限公司 | Novel method for synthesizing ticlopidine hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| NL7801004A (en) | 1978-07-31 |
| SE7800990L (en) | 1978-07-28 |
| JPS5395994A (en) | 1978-08-22 |
| IT1082336B (en) | 1985-05-21 |
| GR63080B (en) | 1979-08-08 |
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