DE1213851B - Process for the preparation of new pharmaceutically valuable thiophene compounds - Google Patents
Process for the preparation of new pharmaceutically valuable thiophene compoundsInfo
- Publication number
- DE1213851B DE1213851B DED40465A DED0040465A DE1213851B DE 1213851 B DE1213851 B DE 1213851B DE D40465 A DED40465 A DE D40465A DE D0040465 A DED0040465 A DE D0040465A DE 1213851 B DE1213851 B DE 1213851B
- Authority
- DE
- Germany
- Prior art keywords
- preparation
- mol
- general formula
- phenyl
- solution
- 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.)
- Pending
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Description
Verfahren zur Herstellung neuer pharmazeutisch wertvoller Thiophenverbindungen Zusatz zum Patent: 1 194424 Das Hauptpatent 1194 424 betrifft ein Verfahren zur Herstellung von Verbindungen der allgemeinen Formel und deren Salzen, wobei in der angegebenen Formel R1 ein Wasserstoffatom oder eine niedrigmolekulare Alkylgruppe und R2 ein Wasserstoff- oder Halogen atom oder eine Hydroxyl- oder eine Alkoxygruppe bedeutet.Process for the production of new pharmaceutically valuable thiophene compounds Addition to patent: 1 194424 The main patent 1194 424 relates to a process for the production of compounds of the general formula and their salts, where in the given formula R1 is a hydrogen atom or a low molecular weight alkyl group and R2 is a hydrogen or halogen atom or a hydroxyl or an alkoxy group.
Diese Verbindungen besitzen eine zentralstimulierende und coronargefäßerweiternde Wirkung. These compounds have a central stimulating and coronary vasodilator function Effect.
Bei der weiteren Ausbildung dieses Verfahrens wurde gefunden, daß man Verbindungen der angegebenen Formel auch dadurch herstellen kann, daß man in an sich bekannter Weise a) eine Verbindung der allgemeinen Formel an Stelle von 2-Thienyllithium mit 2-Thienylmagnesiumbromid umsetzt oder b) eine Verbindung der allgemeinen Formel an Stelle von Phenylmagnesiumbromid mit Phenyllithium umsetzt und gegebenenfalls die erhaltenen Basen in an sich bekannter Weise in ihre Salze überführt.In the further development of this process, it was found that compounds of the formula given can also be prepared by a) a compound of the general formula in a manner known per se in place of 2-thienyllithium with 2-thienylmagnesium bromide or b) a compound of the general formula instead of phenylmagnesium bromide is reacted with phenyllithium and, if appropriate, the bases obtained are converted into their salts in a manner known per se.
Beispiel 1 2-'N-[3-Phenyl-3-thienyl-(2)-3-hydroxy-propyl-(1)]-amino:-3-phenyl-propan Aus 4,8 g (0,2 Mol) Mg-Spänen und 32,6 g (0,2 Mol? 2-Bromthiophen wird in 100 ml absolutem Athe in üblicher Weise die Grignardlösung bereitet. Zu dieser Lösung läßt man 60,6 g (0,2 Mol) 2-IN-[3-Phenyl-3 -oxo-propyl-(l)l-amino)-3 -phenyl-propan-HC1, in 500 ml Ather suspendiert, eintropfen. Die Reaktion ist danach sofort beendet. Es wird mit 50 g Ammoniumchlorid in 150 ml Wasser zersetzt. Die Base wird in ätherischer Lösung mit isopropanolischer HCI neutralisiert. Man erhält 47 g HCI-Salz, das aus Isopropanol umkristallisiert wird. F. 1900C.Example 1 2-'N- [3-Phenyl-3-thienyl- (2) -3-hydroxypropyl- (1)] -amino: -3-phenyl-propane The Grignard solution is prepared in the usual way from 4.8 g (0.2 mol) of Mg turnings and 32.6 g (0.2 mol of 2-bromothiophene in 100 ml of absolute athe. 60.6 g of this solution are added (0.2 mol) 2-IN- [3-phenyl-3-oxo-propyl- (l) l-amino) -3-phenyl-propane-HCl, suspended in 500 ml of ether, drop in. The reaction is then ended immediately. It is decomposed with 50 g of ammonium chloride in 150 ml of water. The base is neutralized in an ethereal solution with isopropanolic HCI. 47 g of HCl salt are obtained, which is recrystallized from isopropanol. F. 1900C.
Beispiel 2 2-{N- [3-Phenyl-3-thienyl-(2)-3-hydroxy-propyl-(1)]-amino)3 -(p-chlprphenyl)-propan Aus 3,5 g (0,145 Mol) Mg-Spänen und 23,6 g (0,145 Mol) 2-Bromthiophen wird in 50 ml absolutem Äther in üblicher Weise die Grignardverbindung bereitet. Diese Lösung wird mit einer Suspension von 23 g (0,068 Mol) (N-[3-p-Chlorphenyl -propyl - (2) - aminoj - äthyl}-phenyl - keton -HCl in 250 ml absolutem Äther versetzt und 4 Stunden gekocht. Anschließend wird mit 20 g Ammoniumchlorid in 100 ml Wasser zersetzt, die Ätherlösung mit Pottasche getrocknet und destilliert. Man erhält 12,8 g Base vom Kp.oa = 250 bis 252"C. In isopropanolischer Lösung wird mit isopropanolischer Maleinsäurelösung ein Maleinat erhalten, das, aus Isopropanol umkristallisiert, bei 145 bis 146"C schmilzt.Example 2 2- {N- [3-phenyl-3-thienyl- (2) -3-hydroxy-propyl- (1)] -amino) 3 - (p-chlorophenyl) -propane The Grignard compound is prepared in the usual way from 3.5 g (0.145 mol) of Mg turnings and 23.6 g (0.145 mol) of 2-bromothiophene in 50 ml of absolute ether. This solution is mixed with a suspension of 23 g (0.068 mol) of (N- [3-p-chlorophenyl-propyl- (2) -aminoj-ethyl} -phenyl-ketone -HCl in 250 ml of absolute ether and the mixture is boiled for 4 hours. Then it is decomposed with 20 g of ammonium chloride in 100 ml of water, the ether solution is dried with potash and distilled. This gives 12.8 g of base with a boiling point of 250 to 252 ° C. In isopropanolic solution with isopropanolic maleic acid solution a maleate is obtained which , recrystallized from isopropanol, melts at 145 to 146 "C.
Beispiel 3 2N- [3-Phenyl-3-thienyl-(2)-3-hydroxy-propyl-(1)]-aminoT-3-(4-methoxv-Dhenvl)-DroDan Aus 6,2 g (0,252 Mol) Mg-Spänen und 41 g (0,252 Mol) 2-Bromthiophen wird in 100 ml abso- gutem Sicher in üblicher Weise die Grignardverbindung bereitet. Dazu läßt man bei 0°C 42 g (0,126 Mol) 2-{N-[3-Phenyl-3-oxo-propyl-(1)]-amino}-3-(4-methoxy-phenyl)-propan-HCl, in 300 ml ababsolutem Äther suspendiert, tropfen. Nach einer halben Stunde wird mit 50 g Ammoniumchlorid in 150 ml Wasser unter Kühlung zersetzt. Die ätherische Lösung wird über Pottasche getrocknet und das HCl-Salz der Base unter Kühlen mit einer Lösung on HCI in Isopropanol gefällt. Nach dem Umkristallisieren aus Essigester-Äthanol (2: 1) erhält man 28 g HCl-Salz vom F. 160 bis 161"C.Example 3 2N- [3-Phenyl-3-thienyl- (2) -3-hydroxy-propyl- (1)] -aminoT-3- (4-methoxv-Dhenvl) -DroDane The Grignard compound is prepared in 100 ml of absolute safety in the usual way from 6.2 g (0.252 mol) of Mg turnings and 41 g (0.252 mol) of 2-bromothiophene. For this purpose, 42 g (0.126 mol) of 2- {N- [3-phenyl-3-oxo-propyl- (1)] -amino} -3- (4-methoxyphenyl) -propane-HCl are allowed at 0 ° C , suspended in 300 ml of absolute ether, drip. After half an hour, 50 g of ammonium chloride in 150 ml of water are used to decompose with cooling. The ethereal solution is dried over potash and the HCl salt of the base is precipitated with a solution of HCl in isopropanol while cooling. After recrystallization from ethyl acetate-ethanol (2: 1), 28 g of HCl salt with a melting point of 160 to 161 ° C. are obtained.
Beispiel 4 2N- [3-Phenyl-3-thienyl-(2)-3-hydroxy-propyl-(1)]-amino}-3-phenyl-propan Aus 2,3 g (0,4 Mol) Lithium und 48 g (0,4 Mol) Brombenzol wird in 200 ml absolutem Äther in üblicher Weise die Phenyllithiumlösung bereitet.Example 4 2N- [3-Phenyl-3-thienyl- (2) -3-hydroxypropyl- (1)] -amino} -3-phenyl-propane The phenyllithium solution is prepared in the usual way from 2.3 g (0.4 mol) of lithium and 48 g (0.4 mol) of bromobenzene in 200 ml of absolute ether.
Diese Lösung wird bei Zimmertemperatur mit einer Suspension von 31 g (0,1 Mol) (2- [3-Phenyl-propyl-(2)-amino]-äthyl}-thienyl-(2)-keton-HCl in 200 ml absolutem Äther versetzt. Nach einer Stunde wird mit 50 g Ammoniumchlorid in 150 ml Wasser zersetzt, die Ätherlösung mit Pottasche getrocknet und das Lösungsmittel abdestilliert. Man erhält 13 g Base vom Kp.1 = 225 bis 235"C. In ätherischer Lösung wird mit isopropanolischer MCl ein Hydrochlorid erhalten, das, aus Isopropanol umkristallisiert, bei 190"C schmilzt.This solution is at room temperature with a suspension of 31 g (0.1 mol) (2- [3-phenyl-propyl- (2) -amino] -ethyl} -thienyl- (2) -ketone-HCl in 200 ml of absolute ether added. After one hour, 50 g of ammonium chloride in 150 ml of water decomposed, the ethereal solution dried with potash and the solvent distilled off. 13 g of base with a boiling point of 225 to 235 ° C. are obtained. In an ethereal solution a hydrochloride is obtained with isopropanolic MCl, which, recrystallized from isopropanol, melts at 190 "C.
Claims (1)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DED37431A DE1194424B (en) | 1961-11-10 | 1961-11-10 | Process for the preparation of basic thiophene derivatives |
| CH1147162A CH429760A (en) | 1961-11-10 | 1962-09-28 | Process for the preparation of new pharmaceutically valuable compounds |
| FI621835A FI42572C (en) | 1961-11-10 | 1962-10-11 | Process for the preparation of therapeutically valuable basic thiophene derivatives |
| BR143797/62A BR6243797D0 (en) | 1961-11-10 | 1962-10-15 | PROCESS TO PRODUCE NEW VALUABLE PHARMACEUTICAL COMPOUNDS |
| GB39127/62A GB970445A (en) | 1961-11-10 | 1962-10-16 | Thiophene derivatives |
| SE11930/62A SE311168B (en) | 1961-11-10 | 1962-11-07 | |
| DK483762AA DK105813C (en) | 1961-11-10 | 1962-11-09 | Process for the preparation of basic thiophene derivatives or salts or quaternary ammonium compounds thereof. |
| DK246264AA DK105595C (en) | 1961-11-10 | 1962-11-09 | Process for the preparation of basic thiophene derivatives or salts or quaternary ammonium compounds thereof. |
| DED40465A DE1213851B (en) | 1961-11-10 | 1962-12-07 | Process for the preparation of new pharmaceutically valuable thiophene compounds |
| BE628104A BE628104A (en) | 1961-11-10 | 1963-02-06 | Process for the preparation of novel phenyl-thienyl-alkanos derivatives |
| SE13233/63A SE309601B (en) | 1961-11-10 | 1963-11-29 | |
| FI691216A FI42577C (en) | 1961-11-10 | 1969-04-24 | Method for the preparation of basic thiophene derivatives affecting the cardiac circulation |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DED37431A DE1194424B (en) | 1961-11-10 | 1961-11-10 | Process for the preparation of basic thiophene derivatives |
| DED40401A DE1199783B (en) | 1962-11-30 | 1962-11-30 | Process for the preparation of basic thiophene derivatives |
| DED40465A DE1213851B (en) | 1961-11-10 | 1962-12-07 | Process for the preparation of new pharmaceutically valuable thiophene compounds |
| DED40471A DE1219038B (en) | 1962-12-08 | 1962-12-08 | Process for the preparation of thiophene compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1213851B true DE1213851B (en) | 1966-04-07 |
Family
ID=45560586
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DED37431A Pending DE1194424B (en) | 1961-11-10 | 1961-11-10 | Process for the preparation of basic thiophene derivatives |
| DED40465A Pending DE1213851B (en) | 1961-11-10 | 1962-12-07 | Process for the preparation of new pharmaceutically valuable thiophene compounds |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DED37431A Pending DE1194424B (en) | 1961-11-10 | 1961-11-10 | Process for the preparation of basic thiophene derivatives |
Country Status (8)
| Country | Link |
|---|---|
| BE (1) | BE628104A (en) |
| BR (1) | BR6243797D0 (en) |
| CH (1) | CH429760A (en) |
| DE (2) | DE1194424B (en) |
| DK (2) | DK105813C (en) |
| FI (2) | FI42572C (en) |
| GB (1) | GB970445A (en) |
| SE (2) | SE311168B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1921453C3 (en) * | 1969-04-26 | 1973-04-19 | Degussa | Basic dithienyl derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB646198A (en) * | 1946-02-28 | 1950-11-15 | Winthrop Stearns Inc | Improvements in or relating to the preparation of antispasmodic agents |
| GB657301A (en) * | 1948-02-25 | 1951-09-19 | Wellcome Found | Improvements in and relating to the preparation of substituted amino-alcohols and derivatives thereof |
| GB702269A (en) * | 1950-01-06 | 1954-01-13 | Wellcome Found | Tertiary allylamines of therapeutic value and the production thereof |
-
1961
- 1961-11-10 DE DED37431A patent/DE1194424B/en active Pending
-
1962
- 1962-09-28 CH CH1147162A patent/CH429760A/en unknown
- 1962-10-11 FI FI621835A patent/FI42572C/en active
- 1962-10-15 BR BR143797/62A patent/BR6243797D0/en unknown
- 1962-10-16 GB GB39127/62A patent/GB970445A/en not_active Expired
- 1962-11-07 SE SE11930/62A patent/SE311168B/xx unknown
- 1962-11-09 DK DK483762AA patent/DK105813C/en active
- 1962-11-09 DK DK246264AA patent/DK105595C/en active
- 1962-12-07 DE DED40465A patent/DE1213851B/en active Pending
-
1963
- 1963-02-06 BE BE628104A patent/BE628104A/en unknown
- 1963-11-29 SE SE13233/63A patent/SE309601B/xx unknown
-
1969
- 1969-04-24 FI FI691216A patent/FI42577C/en active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1921453C3 (en) * | 1969-04-26 | 1973-04-19 | Degussa | Basic dithienyl derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| FI42577C (en) | 1970-09-14 |
| DK105813C (en) | 1966-11-14 |
| FI42572B (en) | 1970-06-01 |
| FI42572C (en) | 1970-09-14 |
| CH429760A (en) | 1967-02-15 |
| BR6243797D0 (en) | 1973-05-24 |
| DE1194424B (en) | 1965-06-10 |
| SE309601B (en) | 1969-03-31 |
| DK105595C (en) | 1966-10-17 |
| BE628104A (en) | 1963-05-29 |
| GB970445A (en) | 1964-09-23 |
| SE311168B (en) | 1969-06-02 |
| FI42577B (en) | 1970-06-01 |
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