DE1145616B - Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituent - Google Patents
Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituentInfo
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- DE1145616B DE1145616B DEC15538A DEC0015538A DE1145616B DE 1145616 B DE1145616 B DE 1145616B DE C15538 A DEC15538 A DE C15538A DE C0015538 A DEC0015538 A DE C0015538A DE 1145616 B DE1145616 B DE 1145616B
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
C 15538 IVb/12 οC 15538 IVb / 12 ο
BEKANNTMACHUNG DER ANMELDUNG UNDAUSGABEDER AUSLEGESCHRIFT: 21. MÄRZ 1963NOTICE THE REGISTRATION ANDOUTPUTE EDITORIAL: MARCH 21, 1963
Die Erfindung betrifft ein Verfahren zur Herstellung von organischen Verbindungen, welche einen mindestens ein Stickstoffatom enthaltenden heterocyclischen Ring als basischen Substituenten tragen. Als organische Verbindungen, in welche der heterocyclische Ring, welcher ein Stickstoffatom enthält, als Substituent eingeführt wird, sind vorzugsweise Phenthiazinverbindungen zu nennen, welche hierdurch N-substituiert werden.The invention relates to a method of manufacture of organic compounds which have a heterocyclic ring containing at least one nitrogen atom as a basic substituent. as organic compounds in which the heterocyclic ring containing a nitrogen atom as Substituent is introduced, phenthiazine compounds are preferred, which thereby N-substituted.
Die Verbindungen dieser Art haben die allgemeine FormelThe compounds of this type have the general formula
ζ CH2 — CH2 s ζ CH 2 - CH 2 s
x CH2- CH2 x x CH 2 - CH 2 x
in welcher R3 einen Alkyl- oder Hydroxyalkylrest, einen Dialkylaminorest, einen Arylrest oder einen heterocyclischen Rest, der neben dem Stickstoffheteroatom als weiteres Heteroatom Schwefel enthalten kann, R2 zwei Wasserstoffatome oder ein Carbonylsauerstoffatom, R1 einen — (CHo)»-Rest, η = 1 bis 6 oder eine unmittelbare einfache CC-Bindung und A einen Alkylaminorest, eine Methylengruppe oder eine Äthersauerstoffbrücke bedeutet.in which R 3 is an alkyl or hydroxyalkyl radical, a dialkylamino radical, an aryl radical or a heterocyclic radical which can contain sulfur as a further heteroatom in addition to the nitrogen heteroatom, R 2 two hydrogen atoms or a carbonyl oxygen atom, R 1 a - (CHo) »radical, η = 1 to 6 or an immediate single CC bond and A denotes an alkylamino radical, a methylene group or an ether-oxygen bridge.
Vorzugsweise ist R3 ein Phenthiazinderivat, dessen N-Atom über eine Alkylenbrücke mit dem ein Stickstoffatom enthaltenden heterocyclischen Ring verbunden ist. R 3 is preferably a phenthiazine derivative whose N atom is connected to the heterocyclic ring containing a nitrogen atom via an alkylene bridge.
Die Verbindungen werden durch hydrierende Kondensation von Nitrilen mit organischen Verbindungen, welche zwei endständige Halogenatome enthalten, in bisher noch nicht bekannter Weise dargestellt. Die organischen Dihalogenverbindungen entsprechen der allgemeinen FormelThe compounds are produced by the hydrogenative condensation of nitriles with organic compounds, which contain two terminal halogen atoms, shown in a previously unknown manner. the organic dihalogen compounds correspond to the general formula
X — CH2 — CH2 \X - CH 2 - CH 2 \
in welcher X Chlor, Brom, Jod, Fluor bedeutet und A die obige Bedeutung hat.in which X is chlorine, bromine, iodine, fluorine and A has the above meaning.
Die hydrierende Kondensation verläuft nach der GleichungThe hydrogenating condensation proceeds according to the equation
X — CH2 — CH2 \X - CH 2 - CH 2 \
R3 — CR2 — R1 — CN +R 3 - CR 2 - R 1 - CN +
X — CH2 — CHjX - CH 2 - CHj
:A: A
R3-CR2-R1-CH2-N
+ 2HXR 3 -CR 2 -R 1 -CH 2 -N
+ 2HX
CH2 — CH2 CH 2 - CH 2
CH2-CH2 CH 2 -CH 2
Verfahren zur HerstellungMethod of manufacture
organischer Verbindungen mit einemorganic compounds with a
mindestens ein Stickstoffatom enthaltendencontaining at least one nitrogen atom
heterocyclischen Ring als basischemheterocyclic ring as a basic
SubstituentenSubstituents
Anmelder:Applicant:
Chemische Fabrik PromontaChemical factory Promonta
Gesellschaft mit beschränkter Haftung,Company with limited liability,
Hamburg 26, Hammer Landstr. 162-178Hamburg 26, Hammer Landstr. 162-178
Dr.-Ing. Ludwig-Wilhelm Masch, Hamburg-Flottbek, und Dr. rer.nat. Rudolf Petersen,Dr.-Ing. Ludwig-Wilhelm Masch, Hamburg-Flottbek, and Dr. rer.nat. Rudolf Petersen,
Hamburg-Duvenstedt,
sind als Erfinder genannt wordenHamburg-Duvenstedt,
have been named as inventors
in welcher R1, R2, R3, A und X die obige Bedeutung haben.in which R 1 , R 2 , R 3 , A and X have the above meaning.
Die erfindungsgemäß herstellbaren Verbindungen sind therapeutisch wertvoll. So eignen sich Phenthiazinverbindungen, welche einen mindestens ein Stickstoffatom enthaltenden heterocyclischen Ring als basischen Ringbestandteil tragen, vorzugsweise zur Behandlung von Psychosen.The compounds that can be prepared according to the invention are therapeutically valuable. Phenthiazine compounds are suitable, which have a heterocyclic ring containing at least one nitrogen atom as carry basic ring component, preferably for the treatment of psychoses.
Wenn ein Kondensationsprodukt, welches den Piperazinring und den Phenthiazinring enthält, hergestellt werden soll, wird ein Phenthiazinalkylnitril mit einem gegebenenfalls in N-Stellung substituierten Dihalogendiäthylamin umgesetzt. Als Alkylnitrile des Phenthiazine sind z. B. das Propionitril, Acetonitril zu nennen. Die Dihalogenverbindung ist z. B. N-Methyl-/3,/3'-dichlordiäthylamin, N-Oxäthyl-ft/S'-dichlordiäthylamin. When a condensation product containing the piperazine ring and the phenthiazine ring is produced is to be, a Phenthiazinalkylnitril with an optionally substituted in the N-position dihalodiethylamine implemented. As alkyl nitriles of phenthiazines, for. B. propionitrile, acetonitrile to call. The dihalo compound is e.g. B. N-methyl- / 3, / 3'-dichlorodiethylamine, N-oxethyl-ft / S'-dichlorodiethylamine.
Die hydrierende Kondensation erfolgt mit Wasserstoff in Gegenwart eines Hydrierungskatalysators und eines basischen Kondensationsmittels, zweckmäßig in einem geeigneten organischen Lösungsmittels, vorzugsweise Dimethylformamid. Als Hydrierungskatalysator dient Raney-Nickel oder Raney-Kobalt, gegebenenfalls mit Kupfer oder Kupfersalzen aktiviert, als Kondensationsmittel vorteilhafterweise Silberverbindungen, wie Silberphosphat, Silbersulfat, Silbercarbonat, Silberoxyd, Silberhydroxyd und basische Stoffe, wie Alkaliverbindungen, ζ. B. Alkalicarbonate und -hydrogen-The hydrogenating condensation takes place with hydrogen in the presence of a hydrogenation catalyst and a basic condensing agent, expediently in a suitable organic solvent, preferably Dimethylformamide. The hydrogenation catalyst used is Raney nickel or Raney cobalt, if appropriate activated with copper or copper salts, advantageously silver compounds as condensation agents, such as silver phosphate, silver sulfate, silver carbonate, silver oxide, silver hydroxide and basic substances such as alkali compounds, ζ. B. Alkali carbonates and -hydrogen-
309 540/438309 540/438
3 43 4
carbonate, -oxyde, -hydroxyde und -amide. Die Hy- carbonat und etwa 30 g Raney-Nickel wurden mitcarbonates, oxides, hydroxides and amides. The carbonate and about 30 g of Raney nickel were used with
drierung wird bei erhöhten Temperaturen und Drücken 500 ecm Cyclohexan vermischt und in einen AutoklavDration is mixed at elevated temperatures and pressures of 500 ecm of cyclohexane and placed in an autoclave
durchgeführt. gebracht. Bei einem Wasserstoffdruck von 50 atü undcarried out. brought. At a hydrogen pressure of 50 atmospheres and
Bei der Herstellung von Kondensationsprodukten bei einer Temperatur von 1000C wurde innerhalb vonIn the production of condensation products at a temperature of 100 0 C was within
von Phentbiazinderivaten mit Piperazinverbindungen 5 6 Stunden die Hydrierung vorgenommen,of phentbiazine derivatives with piperazine compounds 5 carried out the hydrogenation for 6 hours,
ist es bekannt, Dichlordiäthylamin mit einem primären Das Aufarbeiten erfolgte gemäß Beispiel 1. DerIt is known that dichlorodiethylamine with a primary The work-up was carried out according to Example 1. The
Amin umzusetzen, welches über eine Alkylenbrücke erhaltene Basenrückstand wurde in Benzol aufge-To implement amine, the base residue obtained via an alkylene bridge was dissolved in benzene.
an das N-Atom des Phenthiazinringes gebunden ist. nommen und über A}uminiumoxyd nitriert. Das FiI-is bound to the N atom of the phenthiazine ring. and nitrated over A} uminiumoxide. The FiI
Erfindungsgemäß werden nicht die primären Amine, trat wurde vom Lösungsmittel im Vakuum befreit undAccording to the invention, the primary amines are not entered, the solvent was removed in vacuo and
sondern die Nitrile, z. B. Phenthiazinpropionitril, mit io in absolutem Äther aufgenommen. Ätherische SaIz-but the nitriles, e.g. B. Phenthiazinpropionitril, added with io in absolute ether. Ethereal SaIz
Dihalogendialkylaminen unter Hydrierung konden- säure fällte daraus das Hydrochlorid von 3-Chlor-Dihalodialkylamines with hydrogenation of condensate precipitated from them the hydrochloride of 3-chloro
siert. Dieser zweite Weg weist unter anderem die Be- lO-ß'-piperidmo-propyl-lO-phenthiazin, das nach demsated. This second route shows, among other things, the BelLO-ß'-piperidmo-propyl-lO-phenthiazine, which after the
Sonderheit auf, daß das Reaktionsprodukt in der Al- Umkristallisieren aus Aceton—Petroläther bei 171 bisSpecial feature on the fact that the reaction product in the Al recrystallization from acetone-petroleum ether at 171 to
kylengruppe eine Methylengruppe mehr aufweist als 1740C schmolz,kylene group has a methylene group more than 174 0 C melted,
bei Befolgung des bekannten Verfahrens. 15 Beispiel 4by following the known procedure. 15 Example 4
" . . . -. 10-(3'-MorphoHno-propyl-r)-phenthiazin"... -. 10- (3'-MorphoHno-propyl-r) -phenthiazine
,..,,.,„,,,,. . . , ,„ν ,-,η Eine Mischung aus 0,3 Mol 10-(2'-Cyan-äthyl)-phen-, .. ,,., ",,,,. . . ,, "Ν , -, η A mixture of 0.3 mol of 10- (2'-cyano-ethyl) -phen-
10-[3'-(4"-Methyl-piperazmyl-l")-propyl-l ]- thiazin, 0,15 Mol ^'-Dichlor-diäthyläther, 0,3 Mol10- [3 '- (4 "-Methyl-piperazm y ll") -propyl-1] - thiazine, 0.15 mol ^' - dichloro diethyl ether, 0.3 mol
pnentniazin ao silbercarbonat, etwa 60 g Raney-Kobalt, wenig Kup-pnentniazine ao silver carbonate, about 60 g Raney cobalt, a little copper
2,5 Mol 10-(2'-Cyan-äthyl)-phenthiazin und 1 Mol ferchlorür und Kupferpulver und 600 ecm Dimethyl-N-Methyl-^'-dichlor-diäthylamin-hydrochlorid wur- formamid wurde im Autoklav einem Wasserstoffdruck den in 600 ecm Dimethylformamid gelöst und 2 Mol von 90 atü bei einer Temperatur von 140° C 15 Stunden Ag2CO3, 200 g Raney-Kobalt mit weiteren 250 ecm lang ausgesetzt.2.5 mol of 10- (2'-cyano-ethyl) -phenthiazine and 1 mol of ferchloric acid and copper powder and 600 ecm of dimethyl-N-methyl- ^ '- dichloro-diethylamine hydrochloride was formamide in the autoclave to a hydrogen pressure of 600 ecm of dimethylformamide and 2 mol of 90 atmospheres at a temperature of 140 ° C for 15 hours Ag 2 CO 3 , 200 g of Raney cobalt exposed to a further 250 ecm.
Dimethylformamid in den Hochdruckautoklav ge- 25 Die Gewinnung der Base erfolgte wie im Beispiel 3
saugt, 8 Stunden bei 1400C und 100 at Wasserstoff- angegeben. Aus einer Mischung von Aceton und
druck hydriert und anschließend nach Ablassen des Leichtbenzin kristallisierte das Hydrochlorid von
überschüssigen Druckes nach 10 Stunden bei 1400C 10-(3'-MorphoHno-propyl-r)-phenthiazin mit einem
belassen. Das Reaktionsgemisch wurde aus dem Auto- Schmelzpunkt von 125 bis 128 0C aus.
klav genommen, das Lösungsmittel im Vakuum ver- 30Dimethylformamide in the high-pressure autoclave. The base was obtained as suctioned in Example 3, 8 hours at 140 ° C. and 100 atm. Hydrogen. Pressure-hydrogenated from a mixture of acetone and, then, after discharge of the light gasoline, the hydrochloride of the excess pressure crystallized after 10 hours at 140 0 C 10- (3'-MorphoHno-propyl-r) with a -phenthiazin left. The reaction mixture was selected from the auto melting point of 125 to 128 0C .
taken the solvent in a vacuum
dampft und der Rückstand in Chloroform auf- Beispiel 5evaporated and the residue in chloroform - Example 5
genommen. Mit 20%iger Essigsäure wurde die Base . .taken. With 20% acetic acid, the base became. .
daraus extrahiert, durch K2CO3 in Freiheit gesetzt 10-[3-(4"-Methyl-piperazinyl-l")-propyl-l ]-extracted therefrom, set free by K 2 CO 3 10- [3- (4 "-Methyl-piperazinyl-1") - propyl-1] -
und durch mehrfaches Ausäthern abgetrennt. Nach pnentniazinand separated by repeated etherification. According to pnentniazin
dem Abdampfen des Äthers verblieb die Base in etwa 35 0,3 Mol 10-(2'-Cyan-äthyl)-phenthiazin, 0,15 Mol 40%iger Ausbeute. Die freie Base 10-[3'-(4"-Methyl- N - Methyl- ß,ß' - dichlor - diäthylamin - hydrochlorid, piperazinyl-l")-propyl-r]-phentbiazin schmilzt bei 53 0,45 Mol Natriumhydrocarbonat und etwa 60 g Raneybis 56°C, das Dimalonat bei 113 bis 115°C, das Di- Nickel wurden mit 600 ecm Dimethylformamid in den hydrochlorid bei 234 bis 236°C (unter Zersetzung). Autoklav gesogen. Die Hydrierung erfolgte bei einerAfter evaporation of the ether, the base remained in about 0.3 mol of 10- (2'-cyano-ethyl) -phenthiazine, 0.15 mol of 40% yield. The free base 10- [3 '- (4 "-Methyl- N - methyl- ß, ß' - dichloro - diethylamine - hydrochloride, piperazinyl-1") - propyl-r] -phentbiazine melts at 53 0.45 mol of sodium hydrocarbonate and about 60 g Raney at 56 ° C, the dimalonate at 113 to 115 ° C, the di-nickel with 600 ecm of dimethylformamide in the hydrochloride at 234 to 236 ° C (with decomposition). Autoclave sucked. The hydrogenation took place at one
40 Temperatur von 1400C und unter einem Druck von Beispiel 2 40 atü; nach Ablassen des überschüssigen Wasserstoffs40 temperature of 140 0 C and under a pressure of Example 2 40 atü; after releasing the excess hydrogen
m \ii iAf τ" 1 · · 1 λ»\ ι in wurde der Ansatz noch 15 Stunden lang bei 1400Cm \ ii IAF τ "1 · λ 1» \ ι in the batch was still for 15 hours at 140 0 C.
10-[3 -(4 -Isopropyl-piperazinyl-l )-propyl-l ]- he]RSsm, nach dem Abkühlen ffltriert ^ ^n Vaktram 10- [3 - (4 -Isopropyl-piperazinyl-1) -propyl-1] - he ] R S sm, after cooling filtered ^ ^ n Vaktram
pnentniazin yom Lösungsmittel befreit. Der Rückstand wurde in
0,1 Mol 10-(2'-Cyan-äthyl)-phenthiazmund 0,05 Mol 45 200 ecm Chloroform aufgenommen und erschöpfend
N - Isopropyl - ß,ß' - dichlor - diäthylamin - hydrochlorid mit 2 η-Salzsäure extrahiert. Die Base wurde mit Pottwurden
in 600 ecm Dimethylformamid gelöst und asche in Freiheit gesetzt, in Äther aufgenommen
0,1 Mol Ag2CO3, 20 g Raney-Kobalt, je eine Spatel- (3 · 200 ecm), getrocknet und im Vakuum destilliert
spitze aktives Kupferpulver und CuCl mit 150 ecm (Kp.0)1 200 bis 205° C). Die Base, 10-[3'-(4"-Methyl-Dimethylformamid
in den Autoklav gesaugt und 50 piperazinyl-l")-propyl-r]-phenthiazin, konnte nahezu
3 Stunden bei 1300C und 100 at Wasserstoffdruck quantitativ in das Dimalonat vom Schmelzpunkt von
hydriert. Nach Ablassen des überschüssigen Wasser- 113 bis 115°C übergeführt werden. Ausbeute 58
Stoffs wurde noch 10 Stunden auf 130°C weiter er- bis 65%.
hitzt. Die Aufarbeitung erfolgte wie im Beispiel 1 be- Beispiel 6
schrieben. Es wurden erhalten 11g Rohbase, die 55 , „ ,..,,,, , 1N .
entweder durch fraktionierte Destillation oder durch l-Methyl-4-(3'-hydroxy-propyl)-piperazinpnentniazine freed from solvent. The residue was taken up in 0.1 mol of 10- (2'-cyano-ethyl) -phenthiaz and 0.05 mol of 45,200 ecm of chloroform and exhaustively N - isopropyl - ß, ß ' - dichloro - diethylamine - hydrochloride with 2 η-hydrochloric acid extracted. The base was dissolved in 600 ecm of dimethylformamide using pot and ash was released, 0.1 mol of Ag 2 CO 3 , 20 g of Raney cobalt, a spatula (3 x 200 ecm) each, dried and distilled in vacuo sharp active copper powder and CuCl with 150 ecm (bp 0) 1,200 to 205 ° C). The base, 10- [3 '- (4 "-methyl-dimethylformamide sucked into the autoclave and 50 piperazinyl-l") - propyl-r] -phenthiazine, could quantitatively in the nearly 3 hours at 130 0 C and 100 atm hydrogen pressure Dimalonate from the melting point of hydrogenated. After draining off the excess water-113 to 115 ° C are transferred. Yield of 58 substance was further increased to 65% at 130 ° C. for 10 hours.
heats. The work-up was carried out as in Example 1 and Example 6
wrote. 11 g of raw base were obtained which contained 55, ", .. ,,,,, 1N .
either by fractional distillation or by l-methyl-4- (3'-hydroxypropyl) piperazine
Umkristallisieren in Form ihres Dihydrochlorides aus 0,3 Mol Äthylencyanhydrin, 0,45 Mol Natriumhy-Recrystallize in the form of their dihydrochloride from 0.3 mol of ethylene cyanohydrin, 0.45 mol of sodium hy-
absolutem Alkohol gereinigt werden konnte. Die drocarbonat und 0,15MoI N-Methyl-zS^'-dichlor-di-Äusbeute an 10-[3'-(4"-Isopropyl-piperazinyl-l")-pro- äthylamin-hydrochlorid wurden mit 50 g Raney-Nickel pyl-l'l-phenthiazin betrug 35 bis 45°/0· Die Base siedet 60 in 500 ecm Dimethylformamid bei 50 atü und 1400C unter einem Druck von 0,17 mm Quecksilbersäule bei hydriert. Nach 4 Stunden wurde der Wasserstoff bis 205 bis 2100C, das Dihydrochlorid schmilzt bei 240 auf 10 atü abgelassen und das Gemisch 14 Stundencould be cleaned with absolute alcohol. The carbonate and 0.15 mol of N-methyl-zS ^ '- dichloro-di-Äusbeute of 10- [3' - (4 "-Isopropyl-piperazinyl-1") - pro-ethylamine hydrochloride were mixed with 50 g of Raney nickel pyl-l'l-phenthiazine was 35 to 45 ° / 0 · The base boils 60 in 500 ecm dimethylformamide at 50 atm and 140 0 C under a pressure of 0.17 mm mercury with hydrogenated. After 4 hours, the hydrogen was discharged to 205 to 210 ° C., the dihydrochloride melts at 240 to 10 atmospheres and the mixture was released for 14 hours
bis 243°C unter Zersetzung. bei 140°C weiter erhitzt. Das Reaktionsgemisch imup to 243 ° C with decomposition. further heated at 140 ° C. The reaction mixture in
_ . . - , Autoklav wurde nach dem Abkühlen herausgesaugt,_. . -, the autoclave was sucked out after cooling,
eisPie 65 filtriert und das Lösungsmittel im Vakuum abgedampft. Eis P ie 65 filtered and the solvent evaporated in vacuo.
S-CHor-lO-ß'-piperidmo-propyl-lO-phenthiazin Der Rückstand wurde in 250 ecm Chloroform auf-S-CHor-10-ß'-piperidmo-propyl-10-phenthiazine The residue was dissolved in 250 ecm of chloroform
0,157 Mol 3-Chlor-10-(2'-cyan-äthyl)-phenthiazin, genommen und mit 2n-Salzsäure ausgeschüttelt.0.157 mol of 3-chloro-10- (2'-cyano-ethyl) -phenthiazine, taken and extracted with 2N hydrochloric acid.
0,0785 Mol Pentamethylenbromid, 0,157 Mol Silber- Nichtbasische Substanzen wurden durch Ausschütteln0.0785 moles of pentamethylene bromide, 0.157 moles of silver non-basic substances were extracted by shaking
mit wenig Äther entfernt und die wäßrige salzsaure Lösung mit Pottasche alkalisiert. Die Base wurde in Äther aufgenommen, mit_ Pottasche getrocknet, und nach dem Vertreiben des Äthers wurde der Rückstand im Vakuum (Kp.12 125 bis 130° C) destilliert. Das Pikrat des erhaltenen l-Methyl-4-(3'-hydroxy-propyl)-piperazins schmilzt bei 248 bis 250° C unter Zersetzung.removed with a little ether and the aqueous hydrochloric acid solution alkalized with potash. The base was taken up in ether, dried with potash, and after the ether had been driven off, the residue was distilled in vacuo (bp 12 125 to 130 ° C.). The picrate of the l-methyl-4- (3'-hydroxypropyl) piperazine obtained melts at 248 to 250 ° C. with decomposition.
l-Methyl-4-(2'-phenyl-äthyl)-piperazin1-methyl-4- (2'-phenyl-ethyl) piperazine
- 0,43 Mol Benzylcyanid, 0,22 Mol N-Metayl-/3,/?'-dichlor-diäthylamin-hydrochlorid und 0,66 Mol Natriumhydrocarbonat wurden mit 50 g Raney-Nickel und 600 ecm Dimethylformamid in den Autoklav gesaugt und bei einem Wasserstoffdruck von 50 atü und bei einer Temperatur von 50°C hydriert. Die weitere Behandlung erfolgte gemäß Beispiel 6. 1-Methyl-4-(2'-phenyl-äthyl)-piperazin hat den Siedepunkt Kp.12 151 bis 1550C, und sein Dihydrochlorid schmilzt bei 260 bis 2630C.- 0.43 mol of benzyl cyanide, 0.22 mol of N-Metayl- / 3, /? '- dichloro-diethylamine hydrochloride and 0.66 mol of sodium hydrocarbonate were sucked into the autoclave with 50 g of Raney nickel and 600 ecm of dimethylformamide and at hydrogenated at a hydrogen pressure of 50 atmospheres and at a temperature of 50 ° C. The further treatment was done according to Example 6. 1-Methyl-4- (2'-phenyl-ethyl) -piperazine has the boiling point Kp. 12151-155 0 C, and its dihydrochloride melts at 260-263 0 C.
Beispiel 8
l-Methyl-4-(2'-dimethylamino-äthyl)-piperazinExample 8
1-methyl-4- (2'-dimethylamino-ethyl) piperazine
Beispiel 12
l-Methyl-4-(3'-piperidino-propyl-l')-piperazinExample 12
1-methyl-4- (3'-piperidino-propyl-1 ') -piperazine
0,3 Mol N - (2' - Cyan - äthyl) - piperidin, 0,15 Mol N - Methyl - ß,ß' - dichlor - diäthylamin - hydrochlorid, 0,45 Mol Natriumhydrocarbonat und 30 g Raney-Nickel in 500 ecm Dimethylformamid wurden vermischt und gemäß Beispiel 6 weiterverarbeitet. 1-Methyl-4-(3'-piperidino-propyl-l')-piperazm hat den Siedepunkt Kp.17 165 bis 17O0C, und sein Trihydrochlorid schmilzt bei 275 bis 276°C.0.3 mol of N - (2 '- cyano - ethyl) - piperidine, 0.15 mol of N - methyl - ß, ß' - dichloro - diethylamine - hydrochloride, 0.45 mol of sodium hydrocarbonate and 30 g of Raney nickel in 500 ecm Dimethylformamide were mixed and processed according to Example 6. 1-Methyl-4- (3'-piperidino-propyl-1 ') - piperazm has a boiling point of bp 17 165 to 17O 0 C, and its trihydrochloride melts at 275 to 276 ° C.
N,N-Diäthyl-4-morpholinacetamid
0,5 Mol Diäthylaminooxamidsäurenitril, 0,25 Mol ^,/S'-Dichlor-diäthyläther, 0,75 Mol Natriumhydrocarbonat
und 50 g Raney-Nickel wurden nach Beispiel 6 umgesetzt und weiterverarbeitet. N,N-Diäthyl-4-morpholinacetamid
hat den Siedepunkt Kp.19 174 bis 176° C, und sein Hydrochlorid schmilzt bei 186
bis 1870C.N, N-diethyl-4-morpholine acetamide
0.5 mol of diethylaminooxamidsonitrile, 0.25 mol of ^, / S'-dichloro diethyl ether, 0.75 mol of sodium hydrocarbonate and 50 g of Raney nickel were reacted according to Example 6 and processed further. N, N-diethyl-4-morpholinacetamid has the boiling point Kp. 19174-176 ° C, and its hydrochloride melts at 186-187 0 C.
Beispiel 14
9. [3'-(4"-Methyl-piperazinyl- l")-propyl- l']-carbazolExample 14
9. [3 '- (4 "-Methyl-piperazinyl-1") -propyl-1'] - carbazole
0,5 Mol Dimethylaminoacetonitril, 0,25 Mol N-Me- 25 0,5 Mol 9-(2'-Cyan-äthyl)-carbazol, 0,25 Mol N-Me-0.5 mol of dimethylaminoacetonitrile, 0.25 mol of N-Me- 25 0.5 mol of 9- (2'-cyano-ethyl) -carbazole, 0.25 mol of N-Me-
thyl-ßß'-dichlor-diäthylamin-hydrochlorid, 0,75 Mol thyl-^^'-dichlor-diäthylamin-hydrochlorid, 0,75 Molethyl-ßß'-dichloro-diethylamine hydrochloride, 0.75 mol of ethyl - ^^ '- dichloro-diethylamine hydrochloride, 0.75 mol
Natriumhydrocarbonat und 30 g Raney-Nickel wurden Natriumhydrocarbonat und 50 g Raney-Nickel wurdenSodium hydrocarbonate and 30 g of Raney nickel were sodium hydrocarbonate and 50 g of Raney nickel were
gemäß Beispiel 6 behandelt. l-Methyl-4-(2'-dimethyl- mit 600 ecm Dimethylformamid in den AutoklavTreated according to Example 6. 1-methyl-4- (2'-dimethyl- with 600 ecm dimethylformamide in the autoclave
amino-äthyl)-piperazin hat den Siedepunkt Kp.12 93 übergeführt und bei 50 0C und 50 atü wie im Beispiel 6Amino-ethyl) piperazine has the boiling point of bp. 12 93 converted and at 50 0 C and 50 atm as in Example 6
bis 960C; sein Trihydrochlorid schmilzt bei 262 30 hydriert und aufgearbeitet. Neben 9-[3'-(4"-Methyl-to 96 0 C; its trihydrochloride melts at 262 30 hydrogenated and worked up. In addition to 9- [3 '- (4 "-Methyl-
bis 264°C. piperazinyl-l")-propyl-l']-carbazol, das bei 93°Cup to 264 ° C. piperazinyl-l ") - propyl-l '] - carbazole, which is at 93 ° C
BeisDiel 9 schmilzt, entstand als Nebenprodukt eine bei 1300CBeisDiel 9 melts, originated as a by-product at 130 0 C
N,N-Diäthyl-l-methyl-4-piperazinacetamidN, N-diethyl-1-methyl-4-piperazine acetamide
0,45 Mol Diäthylaminooxamidsäurenitril,0.45 mol of diethylaminooxamic acid nitrile,
schmelzende Base. Von dieser konnte die gewünschte Carbazolverbindung durch Umkristallisieren ausmelting base. From this the desired carbazole compound could be obtained by recrystallization
/C2H5 / C 2 H 5
VC2H5 VC 2 H 5
: N · CO · CN: N · CO · CN
Leichtbenzin getrennt werden.Petrol must be separated.
Beispiel 15
9-[3'.(4"-Methyl-piperazinyl-l")-propyl-l']-Example 15
9- [3 '. (4 "-Methyl-piperazinyl-1") -propyl-1'] -
1,2,3,4-tetrahydro-carbazol1,2,3,4-tetrahydro-carbazole
0,22 Mol 9 - (2' - Cyan - äthyl) -1,2,3,4 - tetrahydrocarbazol, 0,11 MolN-Methyl-ß^'-diclüor-diäthylaminhydrochlorid, 0,33 Mol Natriumhydrocarbonat und 30 g Raney-Nickel wurden mit 600 ecm Dimethylformamid in den Autoklav gesogen und bei einem0.22 mol of 9 - (2 '- cyano - ethyl) -1,2,3,4 - tetrahydrocarbazole, 0.11 mol of N-methyl-ß ^ '- diclüor-diethylamine hydrochloride, 0.33 mol of sodium hydrocarbonate and 30 g of Raney nickel were mixed with 600 ecm of dimethylformamide sucked into the autoclave and at one
0,23 Mol N-Methyl-^^'-dichlor-diäthylaminhydrochlorid,
0,69 Mol Natriumhydrocarbonat und 30 g
Raney-Nickel wurden den gleichen Bedingungen wie
im Beispiele unterworfen. Ν,Ν-Diäthyl-l-methyl- 45 Wasserstoffdruck von 50 atü und bei einer Temperatur
4-piperazinacetamid hat den Siedepunkt Kp.14 168 bis von 130° C hydriert. Die Gewinnung des 9-[3'-(4"-Me-172°
C; sein Dihydrochlorid schmilzt bei 214 bis 216°C, thyl - piperazinyl -1") - propyl -1'] -1,2,3,4 - tetrahydrosein
Dimaleat bei 175 bis 176°C. carbazole erfolgte analog Beispiel 6. Sein Dimalonat0.23 mol of N-methyl - ^^ '- dichloro-diethylamine hydrochloride, 0.69 mol of sodium hydrocarbonate and 30 g
Raney nickel were given the same conditions as
in the examples subject. Ν, Ν-Diethyl-l-methyl- 45 hydrogen pressure of 50 atm and at a temperature 4-piperazine acetamide has the boiling point bp. 14 168 hydrogenated to 130 ° C. The recovery of the 9- [3 '- (4 "-Me-172 ° C; its dihydrochloride melts at 214 to 216 ° C, thyl-piperazinyl -1") -propyl -1'] -1,2,3,4 - tetrahydrosein dimaleate at 175 to 176 ° C. carbazole was carried out analogously to Example 6. Its dimalonate
schmilzt bei 134 bis 1360C.melts at 134 to 136 0 C.
Beispiel 10
l-Methyl-4-nonyl-piperazinExample 10
1-methyl-4-nonyl-piperazine
0,5 Mol n-Octylcyanid, 0,25 Mol N-Methyl-/?,/S'-dichlor-diäthylamin-hydrochlorid, 0,75 Mol Natriumhydrocarbonat und 50 g Raney-Nickel in 600 ecm Dimethylformamid wurden wie im Beispiel 6 behandelt. l-Methyl-4-nonyl-piperazin hat den Siedepunkt Kp.0,4 98 bis 1020C, und sein Dihydrochlorid schmilzt bei 261 bis 263° C.0.5 mol of n-octyl cyanide, 0.25 mol of N-methyl - /?, / S'-dichloro-diethylamine hydrochloride, 0.75 mol of sodium hydrocarbonate and 50 g of Raney nickel in 600 ecm of dimethylformamide were treated as in Example 6 . l-methyl-4-nonyl-piperazin has the boiling point Kp. 0, 4, 98 to 102 0 C, and its dihydrochloride melts at 261-263 ° C.
5555
6o6o
Claims (2)
3-Morpholino-propanol-(l)Example 11
3-morpholino-propanol- (l)
haben, in welcher A die obige Bedeutung hat undX - CH 2 - CH 2
have, in which A has the above meaning and
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL109859D NL109859C (en) | 1957-09-27 | ||
| DEC15538A DE1145616B (en) | 1957-09-27 | 1957-09-27 | Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituent |
| CH6395058A CH375013A (en) | 1957-09-27 | 1958-09-15 | Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituent |
| GB3089658A GB901187A (en) | 1957-09-27 | 1958-09-26 | Process of production of organic compounds having as basic substituent a heterocyclic ring containing at least one nitrogen atom |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC15538A DE1145616B (en) | 1957-09-27 | 1957-09-27 | Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1145616B true DE1145616B (en) | 1963-03-21 |
Family
ID=7015858
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEC15538A Pending DE1145616B (en) | 1957-09-27 | 1957-09-27 | Process for the preparation of organic compounds having a heterocyclic ring containing at least one nitrogen atom as a basic substituent |
Country Status (4)
| Country | Link |
|---|---|
| CH (1) | CH375013A (en) |
| DE (1) | DE1145616B (en) |
| GB (1) | GB901187A (en) |
| NL (1) | NL109859C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0420116A2 (en) * | 1989-09-22 | 1991-04-03 | Merrell Pharmaceuticals Inc. | Novel substituted alkyl piperidines and their use as inhibitors of cholesterol synthesis |
| US5350758A (en) * | 1992-07-08 | 1994-09-27 | Merrell Dow Pharmaceuticals Inc. | Piperidyl sulfonamides and sulfoxamides as inhibitors of cholesterol biosynthesis |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1129064E (en) | 1998-11-12 | 2008-01-31 | Invitrogen Corp | Transfection reagents |
| WO2016011203A1 (en) | 2014-07-15 | 2016-01-21 | Life Technologies Corporation | Compositions with lipid aggregates and methods for efficient delivery of molecules to cells |
-
0
- NL NL109859D patent/NL109859C/xx active
-
1957
- 1957-09-27 DE DEC15538A patent/DE1145616B/en active Pending
-
1958
- 1958-09-15 CH CH6395058A patent/CH375013A/en unknown
- 1958-09-26 GB GB3089658A patent/GB901187A/en not_active Expired
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0420116A2 (en) * | 1989-09-22 | 1991-04-03 | Merrell Pharmaceuticals Inc. | Novel substituted alkyl piperidines and their use as inhibitors of cholesterol synthesis |
| EP0420116A3 (en) * | 1989-09-22 | 1991-09-18 | Merrell Dow Pharmaceuticals Inc. | Novel substituted alkyl piperidines and their use as inhibitors of cholesterol synthesis |
| US5350758A (en) * | 1992-07-08 | 1994-09-27 | Merrell Dow Pharmaceuticals Inc. | Piperidyl sulfonamides and sulfoxamides as inhibitors of cholesterol biosynthesis |
| US5489600A (en) * | 1992-07-08 | 1996-02-06 | Wannamaker; Marion W. | Piperidyl amides, sulfonamides and sulfoxamides as inhibitors of cholesterol biosynthesis |
Also Published As
| Publication number | Publication date |
|---|---|
| CH375013A (en) | 1964-02-15 |
| NL109859C (en) | |
| GB901187A (en) | 1962-07-18 |
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