SE203309C1 - - Google Patents
Info
- Publication number
- SE203309C1 SE203309C1 SE203309DA SE203309C1 SE 203309 C1 SE203309 C1 SE 203309C1 SE 203309D A SE203309D A SE 203309DA SE 203309 C1 SE203309 C1 SE 203309C1
- Authority
- SE
- Sweden
- Prior art keywords
- piperidyl
- mixture
- ethyl
- methyl
- phentiazine
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000005245 sintering Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000002026 chloroform extract Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 6
- 229940095064 tartrate Drugs 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- -1 antispasmodics Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Uppfinnare: J Renz, J-P Bourgain och G Schwarz Prioritet begard [rein den 31 jail 1957 (Schweiz) Det har visat sig, att Man kan erhalla i 3-stallfling med lagre alkyltio- resp. aralkyltiogrupper substituerade fentiazinderivat med den allmanna formeln I van i R, betecknar en lagre alkyl- eller aralkylgrupp och R, betecknar en lagre alkylgrupp, genom alt man behandlar tertiara aminer med den allmanna formeln II I " CH, CH, van i R, och R, ha ovan angiven betydelse, med en svaveldihalogenid. Enligt patentet 197 686 framstalles merkapto-fentiazin-derivat med formeln I genom kondensation av merkapto-fentiaziner med 1-halogen-2-(N-alkylpiperidy1-2)-etan. Inventors: J Renz, J-P Bourgain and G Schwarz Priority requested [rein on 31 Jail 1957 (Switzerland) It has been shown that one can obtain in 3-stall flake with lower alkylthio- resp. aralkylthio groups substituted phentiazine derivatives of the general formula I van in R, denote a lower alkyl or aralkyl group and R, denotes a lower alkyl group, by treating tertiary amines of the general formula II I "CH, CH, van in R, and R According to patent 197 686, mercapto-phentiazine derivatives of the formula I are prepared by condensation of mercapto-phentiazines with 1-halo-2- (N-alkylpiperidyl-2) -ethane.
Foremal for patentet 199 324 hr ett fOrfarande for framstallning av merkapto-fentiazin-derivat med formeln I genom dekarboxylering av motsvarande 10-fentiazin-karbonsyraester-derivat. s CH, CH, 2 Foreliggande fOrfarande kan exempelvis genomforas pa sa. satt, att ett N42-(W-alkyl-piperidy1- 2)-ety1-1]-N-[merkapto-fenyll-anilin-derivat tes i ett lampligt organiskt losningsmedel, sasom bensen, toluen eller Iiknande, och under omrorning vid rumstemperatur eller forhojd temperatur sattes med en svaveldihalogenid. Efter avslutad reaktion avdrives losningsmedlet under forminskat tryck och indunstningsaterstoden upptages ef ter utrorning med vatten och alkalilut i ett lampligt, med vatten icke blandbart losningsmedel. Indunstningshterstoden av det organiska skiktet renas forst genom fraktionering i hbgvakuum och kan for ytterligare rening overforas till salt av en lamplig syra. Delta Or speciellt nodvandigt, da utengsmaterialets fenylkarnor Oro substituerade, sá att en blandning av olika isomerer kan bildas vid reaktionen, vilka isomerer skilja sig frail varandra genom substituentens stallning. Skiljning och renframstallning av komponenterna lyckas da genom fraktionerad kristallisation av deras salter. The subject of patent 199 324 is a process for the preparation of mercapto-phentiazine derivatives of the formula I by decarboxylation of the corresponding 10-phentiazine-carboxylic acid ester derivative. s CH, CH, 2 The present process can be carried out, for example, as follows. that an N42- (N-alkyl-piperidyl-2) -ethyl] -N- [mercapto-phenyl-aniline derivative is taken up in a suitable organic solvent, such as benzene, toluene or the like, and with stirring at room temperature. or elevated temperature was set with a sulfur dihalide. After completion of the reaction, the solvent is evaporated off under reduced pressure and the evaporation residue is taken up after stirring with water and alkali liquor in a suitable solvent, water-immiscible solvent. The evaporation residue of the organic layer is first purified by fractionation in a high vacuum and can be transferred to a salt of a suitable acid for further purification. Delta Or is especially necessary when the phenyl nuclei of the outer material Oro are substituted so that a mixture of different isomers can be formed in the reaction, which isomers differ from each other by the arrangement of the substituent. Separation and purification of the components then succeed by fractional crystallization of their salts.
De enligt foreliggande forfarande framstallda, basiska foreningarna Oro vid rumstemperatur oljiga eller kristallina och bilda med syror fasta, bestandiga salter. The basic compounds prepared according to the present process are oily or crystalline at room temperature and form solid, solid salts with acids.
De enligt fOreliggande forfarande framstallda foreningarna ha terapeutiskt anvandbara, farmakodynamiska egenskaper, sasom potensiering av effekten av narkotiskt, hypnotiskt eller analgetiskt verkande farmaka och Oro darfor lampliga for behandling fore narkos. De kunna dessutom anvandas vid allergiska sjukdomar samt sasom sedativum, spasmolytikum, antiemetikum eller neuroplegikum och tjana dessutom fOr behandling av de mest olika retningstillstand. The compounds prepared according to the present method have therapeutically useful pharmacodynamic properties, such as potentiating the effect of narcotic, hypnotic or analgesic drugs and are therefore suitable for the treatment of anesthesia. They can also be used for allergic diseases as well as sedatives, antispasmodics, antiemetics or neuroplegics and also serve to treat the most different irritating conditions.
I fdljande exempel, som askadliggora utfOrandet av fOrfarandet, angivas alla temp eraturuppgifter I celsiusgrader. Smalt- och kokpunkterna Oro okorrigerade. In the following examples, which denote the execution of the procedure, all temperature data are given in degrees Celsius. Melting and boiling points Concerns uncorrected.
Exempel 1. 3-metylmerkapto-10-[2'-(N-metylpiperidy1-2")-ety1-1'1-fentiazin. Example 1. 3-Methylmercapto-10- [2 '- (N-methylpiperidyl-2 ") -ethyl] -1'-fentiazine.
Man loser 340 g N4metylmerkapto-fenyWN[2-(N'-metyl-piperidy1-2')-etyl]-anilin (kokpunkt 216° vid 0,01 mm Hg) i 5000-6000 ml bensen och tillsatter under omrorning en 18sning av 103 g nydestillerad svaveldiklorid i 1000 ml bensen. Efter kort tid avsldljes hydrokloriden. Man later blandningen sta 20 minuter vid rumstemperatur, avdunstar losningsmedlet under forminskat tryck, sa snart reaktionen avslutats, och utror aterstoden med 2500 ml vatten och sa mycket 3 n natronlut, att blandnin en reagerar alkaliskt. De utfallna baserna extraheras genom utskakning tre ganger rued 1000 ml kloroform varje gang, och de over 300-400 g kaliumkarbonat torkade, ftirenade kloroformextrakten indunstas under forminskat tryck. Vid 0,06 mm Hg over& vid temperaturer upp till 225° annu nagot utgangsmaterial. Den vid 0,02 mm Hg och 225-235° 6vergaende huvud- fraktionen innehaller tva isomera baser, som skiljas genom fraktionerad kristallisation av fumaraten. Dissolve 340 g of N4-methylmercapto-phenyl [2- (N'-methyl-piperidyl-2 ') -ethyl] -aniline (b.p. 216 ° at 0.01 mm Hg) in 5000-6000 ml of benzene and add with stirring a solution of 103 g freshly distilled sulfur dichloride in 1000 ml of benzene. After a short time, the hydrochloride precipitates. The mixture is allowed to stand for 20 minutes at room temperature, the solvent is evaporated off under reduced pressure as soon as the reaction is completed, and the residue is stirred with 2500 ml of water and so much 3 n sodium hydroxide solution that the mixture reacts alkaline. The precipitated bases are extracted by shaking three times with 1000 ml of chloroform each time, and the more than 300-400 g of potassium carbonate dried, dehydrated chloroform extracts are evaporated under reduced pressure. At 0.06 mm Hg above & at temperatures up to 225 ° annu some starting material. The main fraction at 0.02 mm Hg and 225-235 ° 6 contains two isomeric bases, which are separated by fractional crystallization of the fumarate.
Man loser 25 g av basblandningen och 8,3 g fumarsyra i 300 ml kokande etanol, filtrerar och later sta vid rumstemperatur, varvid fumaratet av 3-metylmerkapto-10-[2'-(N-metyl-piperidy1- 2")-ety1-11-fentiazin utskiljes kristallint och den isomera foreningen forblir i losning. Efter cmkristallisering ur 100 ml kokande etanol smatter saltet vid 158-160° (sonderdelning). Fumaratet visar icke nagon smaltpunktsnedsattning i blandsmaltpunkt med ett preparat, som framstallts enIigt patentet 197 686. Smaltpunkt hos 3-metylmerkapto-10-[2'-(N-metyl-piperidy1-2")-ety1-11- fentiazin 72-74°. Hydroklorid, smaltpunkt 158160°, sintring frail 153°. Tartratet kristalliserar med 1 mol kristallvatten, smaltpunkt 130° (siinderdelning), sintring Iran 70°. 25 g of the base mixture and 8.3 g of fumaric acid are dissolved in 300 ml of boiling ethanol, filtered and allowed to stand at room temperature, the fumarate of 3-methylmercapto-10- [2 '- (N-methyl-piperidyl-2 ") -ethyl -11-Phentiazine is crystallized out and the isomeric compound remains in solution After crystallization from 100 ml of boiling ethanol, the salt is slurried at 158 DEG-160 DEG C. (probing). Melting point of 3-methylmercapto-10- [2 '- (N-methyl-piperidyl-2 ") - ethyl-11-phentiazine 72-74 °. Hydrochloride, m.p. 158160 °, sintering frail 153 °. The tartrate crystallizes with 1 mole of crystal water, melting point 130 ° (sintering), sintering Iran 70 °.
Exempel 2. 3-etylmerkapto-1042'-(N-metyl-piperidy1-2")-ety1-11-fentiazin. Example 2. 3-Ethylmercapto-1042 '- (N-methyl-piperidyl-2 ") - ethyl-11-fentiazine.
Man loser 354 g N4m-etylmerkapto-fenyll-N[2-(N'-metyl-piperidy1-2)-etyll-anilin (kokpunkt 205° vid 0,005 mm Hg) i 5000-6000 ml bensen och tillsatter under omrorning en losning av 103 g nydestillerad svaveldiklorid i 1000 ml bensen. Efter kort tid avsldlj es hydrokloriden. Man later blandningen sta. 20 minuter vid rumstemperatur, avdriver losningsmedlet under forminskat tryck, sO snart reaktionen avslutats, och utror aterstoden med 2500 ml vatten och sO mycket 3 n natronlut, att blandningen reagerar alkaliskt. Blandningen av utfallna baser extraheras genom utskakning tre ganger med 1000 ml kloroform varje gang, och de Over 300-400 g kaliumkarbonat torkade, f Orenade kloroformextraktea indunstas under f Orminskat tryck. Indunstningsatersto den fraktioneras i hogyakuum. Efter avskiljning av vid 0,008 mm Hg upp till 220° overgaende fordroppar uppsamlar den vid samma tryck och 220-228° destillerande huvudfraktionen. 354 g of N4m-ethylmercapto-phenyl-N [2- (N'-methyl-piperidyl-2) -ethyl] -aniline (boiling point 205 ° at 0.005 mm Hg) are dissolved in 5000-6000 ml of benzene and a solution of 103 g freshly distilled sulfur dichloride in 1000 ml of benzene. After a short time, the hydrochloride is precipitated. The mixture is allowed to stand. 20 minutes at room temperature, evaporate the solvent under reduced pressure, as soon as the reaction is complete, and stir the residue with 2500 ml of water and as much as 3 n sodium hydroxide solution, so that the mixture reacts alkaline. The mixture of precipitated bases is extracted by shaking three times with 1000 ml of chloroform each time, and the Over 300-400 g of potassium carbonate are dried, the crude chloroform extracts are evaporated under reduced pressure. Evaporation residue is fractionated in a hogya vacuum. After separation at 0.008 mm Hg up to 220 ° transient vapor droplets, it collects at the same pressure and 220-228 ° distilling main fraction.
En losning av 20 g basblandning i attiksyraetylester forsattes med en losning av beraknad mangd vinsyra i attiksyraetylester, varvid tartratet av 3-etylmerkapto-1042'-(N-metyl-piperidy1- 2")-ety1-11-fentiazin utfaller. Efter staende vid rumstemperatur avfiltreras, smaltpunkt 135° (sonderdelning), sintring Iran 70°. Blandsmaltpunkt med ett motsvarande preparat, som framstallts enligt patentet 197 686 visar icke nagon smallpunktsdepression. Kokpunkt hos 3-etylmerkapto10- [2' -(N-metyl-piperidy1-2") - ety1-11-fentiazin 225° vid 0,008 mm Hg, smaltpunkt 57-59°. A solution of 20 g of base mixture in attic acid ethyl ester was continued with a solution of an estimated amount of tartaric acid in attic acid ethyl ester, the tartrate of 3-ethylmercapto-1042 '- (N-methyl-piperidyl-2 ") -ethyl1-11-phentiazine precipitating. room temperature is filtered off, melting point 135 ° (probe division), sintering Iran 70 ° Mixing melting point with a corresponding preparation prepared according to patent 197 686 shows no small point depression Boiling point of 3-ethylmercapto10- [2 '- (N-methyl-piperidy1-2 ") - ethyl 11-11-phentiazine 225 ° at 0.008 mm Hg, m.p. 57-59 °.
Exempel 3. 3-n-propylmerkapto-10-[2'-(N-metyl-piperidy1-2")-ety1-11-fentiazin. Example 3. 3-n-propylmercapto-10- [2 '- (N-methyl-piperidyl-2 ") - ethyl-11-phentiazine.
Man loser 368 g N-[m-n-propylmerkapto-fenyli- N12-(r-metyl-piperidy1-2`)-etylFanilin(kok- punkt 198° vid 0,01 mm Hg) i 5000-6000 ml bensen och tillsatter under ()morning en losning av 103 g nydestillerad svaveldiklorid i 1000 ml 3 bensen. Efter kort tid avskilj es hydrokloriden. Man later blandningen sta 20 minuter vid rumstemperatur, avdunstar losningsmedlet under forminskat tryck, sä snart reaktionen avslutats, och utror aterstoden med 2500 ml vaLLen och sá mycket 3 n natronlut, att blandningen reagerar alkaliskt. Blandningen av utfallna baser exLraheras genom tre ganger utskakning med 1000 ml kloroform varje gang, och de Over 300-400 g kaliumkarbonat torkade, forenade kloroformextrakten indunstas under forminskat tryck. Indunstningsaterstoden fraktioneras i hOgvakuum; efter avskiljning av vid 0,01 mm Hg upp till 242° Overgaende fordroppar uppsamlar man den vid samma tryck och vid 242-250° destillerande huvudfraktionen. 368 g of N- [mn-propylmercapto-phenyl] -N12- (r-methyl-piperidyl-2 ') -ethylphaniline (b.p. 198 ° at 0.01 mm Hg) are dissolved in 5000-6000 ml of benzene and added under ( ) morning a solution of 103 g of freshly distilled sulfur dichloride in 1000 ml of 3 benzene. After a short time, the hydrochloride is separated. The mixture is allowed to stand for 20 minutes at room temperature, the solvent is evaporated off under reduced pressure as soon as the reaction is completed, and the residue is stirred with 2500 ml of the well and 3 l of sodium hydroxide solution so that the mixture reacts alkaline. The mixture of precipitated bases is extracted by shaking three times with 1000 ml of chloroform each time, and the Over 300-400 g of potassium carbonate dried, the combined chloroform extracts are evaporated under reduced pressure. The evaporation residue is fractionated in a high vacuum; after separation at 0.01 mm Hg up to 242 ° Transient vapor droplets, it is collected at the same pressure and at 242-250 ° distilling the main fraction.
En losning av 25 g basblandning i 200 ml attiksyraetylester forsattes med en losning av den beraknade mangden vinsyra i attiksyraetylester, varvid tartratet av 3-n-propylmerkapto-10-[2'- (N-metyl-piperidy1-2")-ety1-1Tfentiazin utfaller. Efter staende vid rumstemperatur avfiltreras, smaltpunkt 120° (sonderdelning), sintring fran 70°. Blandsmaltpunkt med ett motsvarande preparat, framstallt enligt patentet 197 686 uppvisar icke flagon smaltpunktsdepression. Kokpunkt hos 3-n-propylmerkapto -10- [2'-(N-metyl-piperidy1- 2-)-ety1-11-fentiazin 247° vid 0,01 mm Hg. A solution of 25 g of base mixture in 200 ml of attic acid ethyl ester was continued with a solution of the calculated amount of tartaric acid in attic acid ethyl ester, the tartrate of 3-n-propylmercapto-10- [2'- (N-methyl-piperidyl-2 ") -ethyl- After standing at room temperature, melting point is filtered off, melting point 120 ° (probe division), sintering from 70 ° Mixing melting point with a corresponding preparation, prepared according to patent 197 686 shows non-flagged melting point depression - (N-methyl-piperidyl-2 -) - ethyl-11-phentiazine 247 ° at 0.01 mm Hg.
Exempel 4. 3-isopropylmerkapto-10-[2'-(N-metyl-piperidy1-2")-etyl-l']-fentiazin. Example 4. 3-Isopropylmercapto-10- [2 '- (N-methyl-piperidyl-2 ") -ethyl-1'] -phentiazine.
Man loser 368 g N4m-isopropylmerkapto-fenyll- N-[2-(N'-metyl-piperidy1-2')-etyll-anilin(kok- punkt 204° vid 0,005 mm Hg) i 5000-6000 ml bensen och tillsatter under omrorning en losning av 103 g nydestillerad svaveldiklorid 1 1000 ml bensen. Efter kort tid avskiljes hydrokloriden. Man later blandningen sta 20 minuter i rumstemperatur, avdunstar losningsmedlet under forminskat tryck, sá snart reaktionen avslutats, och utror aterstoden med 2500 ml vatten och sa mycket 3 n natronlut, att blandningen reagerar alkaliskt. Blandningen av utfallna baser extraheras genom utskakning tre ganger med 1000 ml kloroform varje gang, och de Over 300-400 g kaliumkarbonat torkade, forenade kloroformextrakten indunstas under forminskat tryck. Indunstningsaterstoden fraktioneras i hogvakuum; efter avskiljning av vid 0,005 mm Hg upp till 220° Overgaende fordroppar uppsamlar man den vid samma tryck och vid 220-226° destillerande huvudfraktionen. Dissolve 368 g of N4m-isopropylmercapto-phenyl-N- [2- (N'-methyl-piperidyl-2 ') -ethyl-aniline (b.p. 204 ° at 0.005 mm Hg) in 5000-6000 ml of benzene and add under stirring a solution of 103 g of freshly distilled sulfur dichloride 1 1000 ml of benzene. After a short time, the hydrochloride is separated. The mixture is allowed to stand for 20 minutes at room temperature, the solvent is evaporated off under reduced pressure as soon as the reaction is completed, and the residue is stirred with 2500 ml of water and so much 3 n sodium hydroxide solution that the mixture reacts alkaline. The mixture of precipitated bases is extracted by shaking three times with 1000 ml of chloroform each time, and the Over 300-400 g of potassium carbonate dried, combined chloroform extracts are evaporated under reduced pressure. The evaporation residue is fractionated in a high vacuum; after separation at 0.005 mm Hg up to 220 ° Transient vapor droplets, it is collected at the same pressure and at 220-226 ° distilling the main fraction.
En losning av 22 g basblandning i attiksyraetylester forsattes med en losning av den beraknade mangden vinsyra i attiksyraetylester, varvid tartratet av 3-isopropylmerkapto-1042'-(N-metylpiperidy1-2")-ety1-11-fentiazin utfaller. Efter std.- ende vid rumstemperatur avfiltreras. Smaltpunkt 120° (sonderdelning), sintring frail 70°. Blandsmaltpunkt med ett motsvarande preparat, som framstallts enligt patentet 197 686, visar icke flagon smaltpunktsdepression. Kokpunkt hos 3- isopropylmerkapto -10 -2' - [ (N - metyl - pip eridyl - 2")-ety1-11-fentiazin 223° vid 0,005 mm Hg; smaltpunkt 73-75°. A solution of 22 g of base mixture in attic acid ethyl ester was continued with a solution of the calculated amount of tartaric acid in attic acid ethyl ester, the tartrate of 3-isopropylmercapto-1042 '- (N-methylpiperidyl-2 ") - ethyl1-11-phentiazine precipitating. Melting point 120 ° (probe division), sintering frail 70 ° Mixing melting point with a corresponding preparation prepared according to patent 197 686 shows non-flagged melting point depression Boiling point of 3-isopropylmercapto -10 -2 '- [(N - methyl-piperidyl-2 ") -ethyl-11-phentiazine 223 ° at 0.005 mm Hg; melting point 73-75 °.
Exempel 5. 3-n-butylmerkapto-1042'-(N-metylpiperidy1-2")-etyl-q-fentiazin. Example 5. 3-n-Butylmercapto-1042 '- (N-methylpiperidyl-2 ") - ethyl-q-phentiazine.
Man loser 382 g N4m-n-butylmerkapto-fenyll- N42-(N'-metyl-piperidy1-2)-etyll-anilin(kok- punkt 204° vid 0,01 mm Hg) i 5000-6000 ml bensen och tillsatter under omrorning en losning av 103 g nydestillerad svaveldiklorid i 1000- ml bensen. Efter kort tid avskiljes hydrokloriden. Man later blandningen sta 20 minuter vid rumstemperatur, avdunstar losningsmedlet under f Orminskat tryck, sd snart reaktionen avslutats, och utror aterstoden med 2500 ml vatten och sd mycket 3 n natronlut, att blandningen reagerar alkaliskt. Blandningen av de utfallna baserna extraheras genom utskakning tre ganger med 1000 ml kloroform varje gang, och de Over 300-400 g kaliumkarbonat torkade, forenade kloroformextrakten indunstas under forminskat tryck. Indunstningsaterstoden fraktioneras i hogvakuum. Efter avskiljning av vid 0,005 mm Hg upp till 224° overgaende fordroppar uppsamlar man den vid samma tryck och vid 224-230° destillerande huvudfraktionen. 3-n-butylmerkapto-1042'-(N-metyl-piperidy1-2")-ety1-11-fentiazin kokar vid 227° vid 0,005 mm Hg. 382 g of N4m-n-butylmercapto-phenyl-N42- (N'-methyl-piperidyl-2) -ethyll-aniline (boiling point 204 ° at 0.01 mm Hg) are dissolved in 5000-6000 ml of benzene and added under stirring a solution of 103 g of freshly distilled sulfur dichloride in 1000 ml of benzene. After a short time, the hydrochloride is separated. The mixture is allowed to stand for 20 minutes at room temperature, the solvent is evaporated off under reduced pressure, as soon as the reaction is completed, and the residue is stirred with 2500 ml of water and so much 3N sodium hydroxide solution that the mixture reacts alkaline. The mixture of the precipitated bases is extracted by shaking three times with 1000 ml of chloroform each time, and the Over 300-400 g of potassium carbonate dried, the combined chloroform extracts are evaporated under reduced pressure. The evaporation residue is fractionated in a high vacuum. After separation of vapor droplets at 0.005 mm Hg up to 224 °, it is collected at the same pressure and at 224-230 ° distilling the main fraction. 3-n-Butylmercapto-1042 '- (N-methyl-piperidyl-2 ") - ethyl-11-fentiazine boils at 227 ° at 0.005 mm Hg.
Exempel 6. 3-bensylmerkapto-1042'-(N-metylpiperidy1-2")-ety1-11-fentiazin. Example 6. 3-Benzylmercapto-1042 '- (N-methylpiperidyl-2 ") -ethyl-11-phentiazine.
Man loser 416 g Nqm-bensylmerkapto-fenyll- N-[2-(N`-metyl-piperidy1-2`)-etyll-anilin(kok- punkt 215° vid 0,005 mm Hg) i 5000-6000 ml bensen och tillsatter under omrorning en losning av 103 g nydestillerad svaveldiklorid 11000 ml bensen. Efter kort tid avskiljes hydrokloriden. Man later blandningen s La 20 minuter vid rumstemperatur, avdriver losningsmedlet under forminskat tryck, sá snart reaktionen avslutats, och utror aterstoden med 2500 ml vatten och so. mycket 3 n natronlut, att blandningen reagerar alio.- liskt. Blandningen av utfallna baser extraheras genom utskakning tre ganger med 1000 ml kloroform varje gang, och de Over 300-400 g kaliumkarbonat torkade, fOrenade kloroformextrakten indunstas under fiirminskat tryck. Indunstningsaterstoden fraktioneras i hogvakuum. Efter avskiljning av vid 0,01 mm Hg upp till 242° overgkende fordroppar uppsamlar man den vid samma tryck och vid 242-250° destillerande huvudfraktionen. Dissolve 416 g of Nqm-benzylmercapto-phenyl-N- [2- (N`-methyl-piperidyl-2`) -ethyl] -aniline (b.p. 215 ° at 0.005 mm Hg) in 5000-6000 ml of benzene and add under stirring a solution of 103 g of freshly distilled sulfur dichloride 11000 ml of benzene. After a short time, the hydrochloride is separated. The mixture is allowed to stand for 20 minutes at room temperature, the solvent is evaporated off under reduced pressure as soon as the reaction is completed, and the residue is stirred with 2500 ml of water and so on. very 3 n sodium hydroxide solution, that the mixture reacts alio.- lically. The mixture of precipitated bases is extracted by shaking three times with 1000 ml of chloroform each time, and the Over 300-400 g of potassium carbonate dried, purified chloroform extracts are evaporated under reduced pressure. The evaporation residue is fractionated in a high vacuum. After separation of vapor droplets at 0.01 mm Hg up to 242 °, the main fraction is collected at the same pressure and at 242-250 °.
En losning av 22 g basblandning i 200 ml attiksyraetylester forsattes med en losning av den beraknade mangden vinsyra i attiksyraetylester, varvid tartratet av 3-bensylmerkapto-1012'-(Nmetyl-piperidy1-2")-ety1-11-fentiazin uLfaller. Efter staende vid rumstemperatur avfiltreras. Tartratet innehaller 0,5 mol kristallvatten och smaller vid 105° (sonderdelning), sintring frau 75°. Bland- 4 smaltpunkt med ett motsvarande preparat, som framstallts enligt patentet 197 686, visar joke nagon smaltpunktsnedsattning. Kokpunkt hos 3- bensylmerkapto -10 - [2'- (N- metyl-piperidyl- 2") - ety1-11-fentiazin 246° vid 0,01 mm Hg. A solution of 22 g of base mixture in 200 ml of attic acid ethyl ester was continued with a solution of the calculated amount of tartaric acid in attic acid ethyl ester, whereby the tartrate of 3-benzylmercapto-1012 '- (Nmethyl-piperidyl-2 The tartrate contains 0.5 mol of crystalline water and narrower at 105 ° (probe division), sintering frau 75 °. Mixing melting point with a corresponding preparation, prepared according to patent 197 686, shows the joke no melting point reduction. benzyl mercapto-10 - [2'- (N-methyl-piperidyl-2 ") -ethyl-11-phentiazine 246 ° at 0.01 mm Hg.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE203309T |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SE203309C1 true SE203309C1 (en) | 1965-01-01 |
Family
ID=41987100
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE203309D SE203309C1 (en) |
Country Status (1)
| Country | Link |
|---|---|
| SE (1) | SE203309C1 (en) |
-
0
- SE SE203309D patent/SE203309C1/sv unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4476136A (en) | Aminomethyl-5 oxazolidinic derivatives and therapeutic use thereof | |
| DK149843B (en) | METHOD OF ANALOGUE FOR THE PREPARATION OF 3-SUBSTITUTED 4-PHENYL PIPERIDINES OR SALTS THEREOF WITH PHARMACEUTICAL ACCEPTABLE ACIDS | |
| DK143275B (en) | METHOD OF ANALOGY FOR THE PREPARATION OF 1- (3-DIMETHYLAMINOPROPYL) -PHTHALANDER DERIVATIVES OR ACID ADDITION SALTS THEREOF | |
| ES2794002T3 (en) | Alkynyl pyridine prolyl hydroxylase inhibitor, and method of preparation and medical use thereof | |
| NO116055B (en) | ||
| NO147104B (en) | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE ACETYLENDER DERIVATIVES OF AMINO ACIDS | |
| Toy et al. | d-and l-Polyconidine | |
| Cline et al. | Studies of crystalline vitamin B1. XVII. Synthesis of vitamin B1 | |
| NO128814B (en) | ||
| US4501899A (en) | Resolution of (+)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid using cholesteryl aniline | |
| WO2012065527A1 (en) | Compouds and uses as l-type calcium channel blocker and/or acetylcholinesterase inhibitor thereof | |
| SE203309C1 (en) | ||
| CN105037305B (en) | 5-hydroxy-2 '-nitro aurone or 5-hydroxy-4' -nitro aurone derivative and application thereof | |
| FR2549058A1 (en) | NOVEL 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS | |
| AU2003202104A1 (en) | Carboxamidine derivatives and their use in the treatment of vascular diseases | |
| JPS63165375A (en) | 5-hydroxyethyl derivative of oxazolidinone-2, and its production and therapeutic use | |
| CN101357901B (en) | Chiral 1,4-dihydro-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic carboxylate, preparation method and application thereof | |
| US2744112A (en) | Preparation of optically active 3-hydroxy-n-methyl-morphinanes | |
| FR2462438A1 (en) | NOVEL DERIVATIVES OF 6-ALKYL-7-PHENYL-1,6-NAPHTHYRIDINE-5 (6H) -ONE, THEIR PREPARATION AND THEIR APPLICATION AS MEDICAMENTS | |
| PL106888B1 (en) | METHOD OF PRODUCTION OF NEW 2-PENYL DI-CYCLATE AND OCTENE DERIVATIVES | |
| JPH01311060A (en) | 3, 4-dihydroxy-2-pyroliginone derivative | |
| CZ239496A3 (en) | Substituted 4h-pyrans, process of their preparation, their use and pharmaceutical composition containing thereof | |
| FR2523128A1 (en) | NOVEL 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PREPARATION AND MEDICAMENTS CONTAINING THESE DERIVATIVES | |
| NO143785B (en) | PROCEDURE FOR HEAT EXTRACTION OF ALUMINUM ALLOYS WITH HIGH STRENGTH | |
| KR20170134505A (en) | Composition for the treatment of kidney and / or liver disease |