CA1052794A - Method of producing n-methyl-n-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine - Google Patents
Method of producing n-methyl-n-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamineInfo
- Publication number
- CA1052794A CA1052794A CA226,057A CA226057A CA1052794A CA 1052794 A CA1052794 A CA 1052794A CA 226057 A CA226057 A CA 226057A CA 1052794 A CA1052794 A CA 1052794A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- trimethoxybenzyl
- pentadienamine
- trimethyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A method of producing an anglgesic comprising N-methyl-N-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine having the formula:
(I) characterized in that, in a first stage, 3,4,5-trimethoxy-benzyl chloride having the formula is caused to react with 1,3,4,-trimethyl-1,2,5,6-tetra-hydropyridine having the formula in a anhydrous solvent at the reflux temperature of the mixture, so that upon cooling there is obtained 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6-tetrahydro-pyridine chloride having the formula:
A method of producing an anglgesic comprising N-methyl-N-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine having the formula:
(I) characterized in that, in a first stage, 3,4,5-trimethoxy-benzyl chloride having the formula is caused to react with 1,3,4,-trimethyl-1,2,5,6-tetra-hydropyridine having the formula in a anhydrous solvent at the reflux temperature of the mixture, so that upon cooling there is obtained 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6-tetrahydro-pyridine chloride having the formula:
Description
105~79~ ~
-. The present invention relates to the production of ~-N-methyl-N~(3,4,5-trimethoxybenzyl)-2, 3-dimethyl-2,~
pentadienamine having the general formula :
: 3 .,~ ~ , .
CII30 ~ 0 ~ C~2 ,~ 3 (I) . 3 ~ ~ ~ ~
CII3 . :
~ . . .
its pharmaceutically acceptable acid-addition salts, for example its hydrochloride, and an intermediate compound for preparing it: l,3,4-trimethyl-l-(3,4,5-trimethoxybenzyl)-l,2,5,6-tetra-~i1 hydropyridine chloride, having the formula ~! 3 ~ C~l2 Cl ~ C~13 (~I) A ~;
. CH3 ~ 1 ~ .
:.. , ~ . . .
~ CII
', -These compounds have interesting pharmaceutical properties as analgèsir~s. ~
The method of the invention consists in reacting, in ~ .
a first synthesis stage, 3,4,5-trimethoxybenzyl chloride having the formula `~
,~. ':
i ':
., . --1-- , .
. ! , '- .;
'''`" -S~7~
i .
~ `
; ,,.~ -:
,:,., CII 2 - C l ' ,~, ,~ ,~
OCH3/ j 3 I with 1,3,~-trimethyl-1,2,5,6-tetrahydropyridine having the .1 formula .. ~ i .; CM3 :
.,.~" I ,, ... . / N \
"~ 1 ,' ~ CH3~ ~
CH
,. 3 .:
in the anhydrous solvent kept at reflux, for example acetone, '~ which results in ~he production of the above-mentioned com- ,~`
pound II when the reaction mixture is cooled. `
In a second synthesis stage, the ammonium salt of ;"~ formula II thus obtained is subjected to a Hofmann degradation reaction by prolonged boiling with an aqueous solution of an . ., ~,, . ~ . ; .
alkaline metal hydroxide, for example potassium hydroxide.
Extraction with ether and subsequent treatment with ether and a hydracid acid results in the halohydride of the corresponding ~ .
compound having the formula I.
, 20 The following Examples are given me.rely by way of :' illustration and the scope of the invention is in no way , limited thereby.
:~, 2 ,"'' ~ .
, 1 , ., . . . . " . . .... . ..
6)5;~7~
~_a~e ]
Production of 1,3,~-trimethyl-1-(3,4_5-trimethox~benzyl? ;~
-1,2,5,6-tetrah ~ro~ lorlcle (II).
55 g of 3,4,5-trimethoxyberlæyl chloride dissolved in 200 ml o~ anhydrous acetone were added rapidly and while being stirred to a solution o~ 30 g of 1,3,4-trimethyl-1,2,5,6-tetrahydro-~- pyridine in 150 ml of an~ydroùs acetone. The mix-ture was heated for 5 hours to reflux. The mixture was allowed to cool and .. ..
stirring was continued for 2 hours while the mixture was main-,.~ ; .
tained at a low temperature. Finally, i-t was left in the cool-, i,~ , ing apparatus. The precipitate obtained was washed with acetone-ether (1:1), giving 79 g of II. Y$eld = 92%. An analytical sample crystallized in acetone absolute alcohol had ;~ a melting point of 149 - 152C. Analysis: Cl~H28NO3Cl.H2O.
Calculated: C = 60.08, H = $.~0, N ~ 3.89. Actual: C =
'`~1 , . ' .
59.90, H = 8.38~ N = 3.85.
ample 2 .
., :.
Production of N-methyl-N-(3,4,5-trlmethoxybenzy~L~3-dimeth~ ,a-pentadienamine (I), and its hydroch _ride.
16.2 CJ of 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2, 5,6-tetrahydropyridine chloride (II), 25.2 y of po~assium hydroxide and 145 ml of water were kept at reflux for 33 hours, :1 :
~ the separation of an or~anic layer being observed~ Thereafter . . , extraction with ether and drying with anhydrous sodi~ sulphate were carried out. An ethereal solution of dry hydrochloric acid was added drop by drop until an acid pH was reached, and ,..................................................................... ... .
:, '`~ i :, :
~ 3 , ,1 .
,,~ ,, .
~ . .
: ~Q5'~7S~
~ 9 g of the hyc1rochlorid~ of the compound of formula I were - precipitated. Melting point 3 202 - 20~C.
, :; , , While maintaining the ac~ueous layer at reflux during a further 45 hours, treatment similar to that described in the previous paragraph was continued and a further 2.1 g of hydro-chloride were o~tained, thus giving a total yielcl of 72~.
Analysis: C18H2~O3Cl- Calculated: C = 63.24, H - ~.25, N = 4.09. Actual: C = 63.09, Il = ~.27, N - 4.12.
i~- PROPERTIES OF T~lE PRODUCTS IN ACCORDANCE WIT~ THE INVENTION
r Products /'", ~ .
I - N-methyl-N-~3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-` pentadienamine.
: - .
II - 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6--~` tetrahydropyridine chloride.
''; :`
~ These products have analgesic properties; studies were `, carried out with dextropropoxiphene as a reference analgesic.
, ; A - ACUTE TOXICITY
,' --The acute toxicity studies were carriecl out on I.C.R.
Swiss mice of both sexes and weighing 30+2gr the products were administered intraperitoneally (i.p.). The acute toxicity calculations were carried out by the Litchfield Wilcoxon method.
:
TABLE ~
,'. ' , _ ~ .' ProductsLethal dose 50 (LD50) `:3~ I 165 mg/kg II 77 mg/]cg Dextropropoxiphene 140 mg/kg :.
~ : ,.
, ~ , . : . , . : . , - ~5f~7~3~
B - ~N~LGESIC ACTIVITY
., .
.~i ,, i~ The anal~esic effect was studied in I.C.R. Swiss albino ,~ mice, using ~he acetic acid writhirlg technique. Batches of 10 mice were treated.
The analgesics were injected i.p. and after 30 minutes 0.25 rnl of 1% acetic acid were injected i.p. A control batch which received only acetic acid was used. The number of writhes . .. - ~., ,. ~
in each mouse during the 20 minutes follo~ng the administration ,-of acetic acid were counted.
TABLE B
5~ :
~, Treatment Dose No. of writhes P
~i _ + ,~ ~.
- (x - S.E.M.)*
I 20 mg/kg 54.1 - 4.65p ~ 0.001 - II , 20 mg/ky 53.6 4.7 p~ 0.001 - Dextroprop-- oxiphene 25 mg/kg 22.8 - 4.74p ~ 0.001 ' Control --- 112.2 + 4.2 : , .. . .
. 3 ~( * Mean value - standard error of averaye.
~ . . . .
;.-As can be seen from Table B, products I and II have . j . .
' analgesic activity.
.~ ,.,, ~ , Listed below are examples of pharmaceutical compositions ~`~ containing as active ingredients the following products, combined with carriers and pharmaceutical excipients.
.,,,. ~, :
;`~ I - N-methyl-N-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine and its hydrochloride. ;
, II - 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl~-1,2,5,6-~`~ tetrahydropyridine chloride.
. . 1 , .~ . , .,. . ,~
7~4 The oral dose of product I is 2.23 m~ per kg of weight and per day. ~n indiviclual weighing 70 k~ will he a~ninistered .:i 150 mg daily, spread over three doses of 50 m~
The injectable do~e of compou~d I is 1.5 mg per k~ of weight and per day. An individual weighing 70 kg will be administered 105 my claily, spread over three injections of 35 mg each.
The oral dose of product II is similar to the preceding ;'.~,'! one.
, ..................................................................... .
..... . .
~ 10 EXAMPLE 1 ;~ ~Iard gelatlne capsules. Composition per capsule: ~`
-;i N-methyl-N~(3,~,5-trimethoxybenzyl)-2,3-dimethyl-2,~-pentadienamine or its hydrochloride...................... ...50 mg Lactose O~ 100 mg ` Magnesium stearate ............ ~........ -.- 2.5 mg , , .
EXAMPLE_2 ,~
,I Injectable solution. Composition per ampoule:
:,, .
N-methyl-N-(3, a, 5-trimethoxybenzyl)-2,3-dimethyl-2,4-` pentadienamine hydrochloride .. .. 35 mg ; 20 Sodium chloride................... 27 mg .... .
Sodium metabisulphite ............ .3 mg !,", Water for injectables ............ .3 ml EXA~LE 3 ~" Hard gelatine capsules. Composition per capsule:
'' 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl) 1,2,5,6-tetrahydropyridine chloride .... ~. 50 mg Lactose ........................ ~ 100 mg Magnesium stearate ............... 2.5 mg .~
ii -6-., ;
.,.
."
-. The present invention relates to the production of ~-N-methyl-N~(3,4,5-trimethoxybenzyl)-2, 3-dimethyl-2,~
pentadienamine having the general formula :
: 3 .,~ ~ , .
CII30 ~ 0 ~ C~2 ,~ 3 (I) . 3 ~ ~ ~ ~
CII3 . :
~ . . .
its pharmaceutically acceptable acid-addition salts, for example its hydrochloride, and an intermediate compound for preparing it: l,3,4-trimethyl-l-(3,4,5-trimethoxybenzyl)-l,2,5,6-tetra-~i1 hydropyridine chloride, having the formula ~! 3 ~ C~l2 Cl ~ C~13 (~I) A ~;
. CH3 ~ 1 ~ .
:.. , ~ . . .
~ CII
', -These compounds have interesting pharmaceutical properties as analgèsir~s. ~
The method of the invention consists in reacting, in ~ .
a first synthesis stage, 3,4,5-trimethoxybenzyl chloride having the formula `~
,~. ':
i ':
., . --1-- , .
. ! , '- .;
'''`" -S~7~
i .
~ `
; ,,.~ -:
,:,., CII 2 - C l ' ,~, ,~ ,~
OCH3/ j 3 I with 1,3,~-trimethyl-1,2,5,6-tetrahydropyridine having the .1 formula .. ~ i .; CM3 :
.,.~" I ,, ... . / N \
"~ 1 ,' ~ CH3~ ~
CH
,. 3 .:
in the anhydrous solvent kept at reflux, for example acetone, '~ which results in ~he production of the above-mentioned com- ,~`
pound II when the reaction mixture is cooled. `
In a second synthesis stage, the ammonium salt of ;"~ formula II thus obtained is subjected to a Hofmann degradation reaction by prolonged boiling with an aqueous solution of an . ., ~,, . ~ . ; .
alkaline metal hydroxide, for example potassium hydroxide.
Extraction with ether and subsequent treatment with ether and a hydracid acid results in the halohydride of the corresponding ~ .
compound having the formula I.
, 20 The following Examples are given me.rely by way of :' illustration and the scope of the invention is in no way , limited thereby.
:~, 2 ,"'' ~ .
, 1 , ., . . . . " . . .... . ..
6)5;~7~
~_a~e ]
Production of 1,3,~-trimethyl-1-(3,4_5-trimethox~benzyl? ;~
-1,2,5,6-tetrah ~ro~ lorlcle (II).
55 g of 3,4,5-trimethoxyberlæyl chloride dissolved in 200 ml o~ anhydrous acetone were added rapidly and while being stirred to a solution o~ 30 g of 1,3,4-trimethyl-1,2,5,6-tetrahydro-~- pyridine in 150 ml of an~ydroùs acetone. The mix-ture was heated for 5 hours to reflux. The mixture was allowed to cool and .. ..
stirring was continued for 2 hours while the mixture was main-,.~ ; .
tained at a low temperature. Finally, i-t was left in the cool-, i,~ , ing apparatus. The precipitate obtained was washed with acetone-ether (1:1), giving 79 g of II. Y$eld = 92%. An analytical sample crystallized in acetone absolute alcohol had ;~ a melting point of 149 - 152C. Analysis: Cl~H28NO3Cl.H2O.
Calculated: C = 60.08, H = $.~0, N ~ 3.89. Actual: C =
'`~1 , . ' .
59.90, H = 8.38~ N = 3.85.
ample 2 .
., :.
Production of N-methyl-N-(3,4,5-trlmethoxybenzy~L~3-dimeth~ ,a-pentadienamine (I), and its hydroch _ride.
16.2 CJ of 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2, 5,6-tetrahydropyridine chloride (II), 25.2 y of po~assium hydroxide and 145 ml of water were kept at reflux for 33 hours, :1 :
~ the separation of an or~anic layer being observed~ Thereafter . . , extraction with ether and drying with anhydrous sodi~ sulphate were carried out. An ethereal solution of dry hydrochloric acid was added drop by drop until an acid pH was reached, and ,..................................................................... ... .
:, '`~ i :, :
~ 3 , ,1 .
,,~ ,, .
~ . .
: ~Q5'~7S~
~ 9 g of the hyc1rochlorid~ of the compound of formula I were - precipitated. Melting point 3 202 - 20~C.
, :; , , While maintaining the ac~ueous layer at reflux during a further 45 hours, treatment similar to that described in the previous paragraph was continued and a further 2.1 g of hydro-chloride were o~tained, thus giving a total yielcl of 72~.
Analysis: C18H2~O3Cl- Calculated: C = 63.24, H - ~.25, N = 4.09. Actual: C = 63.09, Il = ~.27, N - 4.12.
i~- PROPERTIES OF T~lE PRODUCTS IN ACCORDANCE WIT~ THE INVENTION
r Products /'", ~ .
I - N-methyl-N-~3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-` pentadienamine.
: - .
II - 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6--~` tetrahydropyridine chloride.
''; :`
~ These products have analgesic properties; studies were `, carried out with dextropropoxiphene as a reference analgesic.
, ; A - ACUTE TOXICITY
,' --The acute toxicity studies were carriecl out on I.C.R.
Swiss mice of both sexes and weighing 30+2gr the products were administered intraperitoneally (i.p.). The acute toxicity calculations were carried out by the Litchfield Wilcoxon method.
:
TABLE ~
,'. ' , _ ~ .' ProductsLethal dose 50 (LD50) `:3~ I 165 mg/kg II 77 mg/]cg Dextropropoxiphene 140 mg/kg :.
~ : ,.
, ~ , . : . , . : . , - ~5f~7~3~
B - ~N~LGESIC ACTIVITY
., .
.~i ,, i~ The anal~esic effect was studied in I.C.R. Swiss albino ,~ mice, using ~he acetic acid writhirlg technique. Batches of 10 mice were treated.
The analgesics were injected i.p. and after 30 minutes 0.25 rnl of 1% acetic acid were injected i.p. A control batch which received only acetic acid was used. The number of writhes . .. - ~., ,. ~
in each mouse during the 20 minutes follo~ng the administration ,-of acetic acid were counted.
TABLE B
5~ :
~, Treatment Dose No. of writhes P
~i _ + ,~ ~.
- (x - S.E.M.)*
I 20 mg/kg 54.1 - 4.65p ~ 0.001 - II , 20 mg/ky 53.6 4.7 p~ 0.001 - Dextroprop-- oxiphene 25 mg/kg 22.8 - 4.74p ~ 0.001 ' Control --- 112.2 + 4.2 : , .. . .
. 3 ~( * Mean value - standard error of averaye.
~ . . . .
;.-As can be seen from Table B, products I and II have . j . .
' analgesic activity.
.~ ,.,, ~ , Listed below are examples of pharmaceutical compositions ~`~ containing as active ingredients the following products, combined with carriers and pharmaceutical excipients.
.,,,. ~, :
;`~ I - N-methyl-N-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine and its hydrochloride. ;
, II - 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl~-1,2,5,6-~`~ tetrahydropyridine chloride.
. . 1 , .~ . , .,. . ,~
7~4 The oral dose of product I is 2.23 m~ per kg of weight and per day. ~n indiviclual weighing 70 k~ will he a~ninistered .:i 150 mg daily, spread over three doses of 50 m~
The injectable do~e of compou~d I is 1.5 mg per k~ of weight and per day. An individual weighing 70 kg will be administered 105 my claily, spread over three injections of 35 mg each.
The oral dose of product II is similar to the preceding ;'.~,'! one.
, ..................................................................... .
..... . .
~ 10 EXAMPLE 1 ;~ ~Iard gelatlne capsules. Composition per capsule: ~`
-;i N-methyl-N~(3,~,5-trimethoxybenzyl)-2,3-dimethyl-2,~-pentadienamine or its hydrochloride...................... ...50 mg Lactose O~ 100 mg ` Magnesium stearate ............ ~........ -.- 2.5 mg , , .
EXAMPLE_2 ,~
,I Injectable solution. Composition per ampoule:
:,, .
N-methyl-N-(3, a, 5-trimethoxybenzyl)-2,3-dimethyl-2,4-` pentadienamine hydrochloride .. .. 35 mg ; 20 Sodium chloride................... 27 mg .... .
Sodium metabisulphite ............ .3 mg !,", Water for injectables ............ .3 ml EXA~LE 3 ~" Hard gelatine capsules. Composition per capsule:
'' 1,3,~-trimethyl-1-(3,4,5-trimethoxybenzyl) 1,2,5,6-tetrahydropyridine chloride .... ~. 50 mg Lactose ........................ ~ 100 mg Magnesium stearate ............... 2.5 mg .~
ii -6-., ;
.,.
."
Claims (7)
1. A method of producing N-methyl-N-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine having the formula (i) characterized in that, in a first stage, 3,4,5-trimethoxy-benzyl chloride having the formula is caused to react with 1,3,4,trimethyl-1,2,5,6-tetra-hydropyridine having the formula in a anhydrous solvent at the reflux temperature of the mixture, so that upon cooling there is obtained 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6-tetrahydro-pyridine chloride having the formula (II) and thereafter the compound having the formula II is subjected to a Hofmann degradation reaction by prolonged boiling treatment with an aqueous solution of an alkaline metal hydroxide which results in the formula I compound, mentioned above, being obtained, and this being optionally converted into a pharmaceutically acceptable salt such as the hydrochloride.
2. A method according to Claim 1, characterized in that the anhydrous solvent used in the first synthesis stage is anhydrous acetone.
3. A method according to Claim 1, characterized in that potassium hydroxide is used as the alkaline hydroxide in the second synthesis stage.
4. The compound N-methyl-N (3,4,5-trimethoxybenzyl)-2, 3-dimethyl-2,4-pentadienamine when prepared according to the method of Claim 1.
5. The compound N-methyl-N-(3,4,5-trimethoxybenzyl)-2, 3-dimethyl-2,4-pentadienamine when prepared according to the method of Claim 2.
6. The compound N-methyl-N-(3,4,5-trimethoxybenzyl)-2, 3-dimethyl-2,4-pentadienamine when prepared according to the method of Claim 3.
7. A method of producing 1,3,4-trimethyl-1-(3,4,5-trimethoxybenzyl)-1,2,5,6-tetrahydropyridine chloride comprising, reacting 3,4,5-trimethoxy-benzyl chloride, having the formula with 1,3,4,-trimethyl-1,2,5,6-tetrahydropyridine having the formula in a anhydrous solvent at the reflux temperature of the mixture.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES425970A ES425970A1 (en) | 1974-05-04 | 1974-05-04 | Pharmaceutically active amines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1052794A true CA1052794A (en) | 1979-04-17 |
Family
ID=8466594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA226,057A Expired CA1052794A (en) | 1974-05-04 | 1975-05-01 | Method of producing n-methyl-n-(3,4,5-trimethoxybenzyl)-2,3-dimethyl-2,4-pentadienamine |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5337337B2 (en) |
| AR (1) | AR206623A1 (en) |
| AT (1) | AT337160B (en) |
| AU (1) | AU8050775A (en) |
| BE (1) | BE828240A (en) |
| CA (1) | CA1052794A (en) |
| CH (1) | CH615150A5 (en) |
| DE (1) | DE2518534A1 (en) |
| ES (1) | ES425970A1 (en) |
| FR (1) | FR2269336B1 (en) |
| GB (1) | GB1501153A (en) |
| NL (1) | NL7505254A (en) |
| SE (1) | SE412755B (en) |
| SU (1) | SU562192A3 (en) |
-
1974
- 1974-05-04 ES ES425970A patent/ES425970A1/en not_active Expired
-
1975
- 1975-01-01 AR AR257859A patent/AR206623A1/en active
- 1975-03-07 AT AT181075A patent/AT337160B/en not_active IP Right Cessation
- 1975-04-15 SE SE7504301A patent/SE412755B/en unknown
- 1975-04-15 GB GB15514/75A patent/GB1501153A/en not_active Expired
- 1975-04-22 BE BE155654A patent/BE828240A/en unknown
- 1975-04-24 AU AU80507/75A patent/AU8050775A/en not_active Expired
- 1975-04-25 DE DE19752518534 patent/DE2518534A1/en active Pending
- 1975-04-30 FR FR7513536A patent/FR2269336B1/fr not_active Expired
- 1975-05-01 CA CA226,057A patent/CA1052794A/en not_active Expired
- 1975-05-02 JP JP5380075A patent/JPS5337337B2/ja not_active Expired
- 1975-05-02 NL NL7505254A patent/NL7505254A/en not_active Application Discontinuation
- 1975-05-02 CH CH568075A patent/CH615150A5/en not_active IP Right Cessation
- 1975-05-04 SU SU2129803A patent/SU562192A3/en active
Also Published As
| Publication number | Publication date |
|---|---|
| FR2269336B1 (en) | 1977-09-09 |
| SE7504301L (en) | 1975-11-05 |
| SU562192A3 (en) | 1977-06-15 |
| NL7505254A (en) | 1975-11-06 |
| AR206623A1 (en) | 1976-08-06 |
| AT337160B (en) | 1977-06-10 |
| FR2269336A1 (en) | 1975-11-28 |
| JPS50151835A (en) | 1975-12-06 |
| ATA181075A (en) | 1976-10-15 |
| GB1501153A (en) | 1978-02-15 |
| CH615150A5 (en) | 1980-01-15 |
| BE828240A (en) | 1975-10-22 |
| SE412755B (en) | 1980-03-17 |
| AU8050775A (en) | 1976-10-28 |
| JPS5337337B2 (en) | 1978-10-07 |
| DE2518534A1 (en) | 1975-11-13 |
| ES425970A1 (en) | 1976-09-16 |
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