IES940271A2 - "A process for producing pharmaceutical compounds" - Google Patents

"A process for producing pharmaceutical compounds"

Info

Publication number
IES940271A2
IES940271A2 IE027194A IES940271A IES940271A2 IE S940271 A2 IES940271 A2 IE S940271A2 IE 027194 A IE027194 A IE 027194A IE S940271 A IES940271 A IE S940271A IE S940271 A2 IES940271 A2 IE S940271A2
Authority
IE
Ireland
Prior art keywords
selegiline
hci
phenylisopropylamine
added
solvent
Prior art date
Application number
IE027194A
Inventor
Helmut Schickaneder
Aggelos Nikolopoulos
Original Assignee
Russinsky Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Russinsky Ltd filed Critical Russinsky Ltd
Priority to IE027194 priority Critical patent/IES61604B2/en
Priority to IE940543A priority patent/IE940543A1/en
Priority to GB9413847A priority patent/GB2284810B/en
Publication of IES940271A2 publication Critical patent/IES940271A2/en
Publication of IES61604B2 publication Critical patent/IES61604B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
    • C07C209/08—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Phenylisopropylamine derivatives are prepared by introducing a propargyl or 2-halo-propenyl radical into a suitable compound in the presence of a solvent and a tertiary amine base. Thus selegiline (I) is prepared from methamphetamine (II) and propargyl bromide in the presence of toluene and diisopropylethylamine.

Description

A process for producing pharmaceutical compounds The invention relates to an industrial process for producing pharmaceutical compounds and in particular to a process for producing phenylisopropylamine derivatives.
Phenylisopropylamine derivatives have been known since 1965. British Patent Specification No. 1,153,578 describes the Monoamine Oxidase inhibitor (MAO-inhibitor) activities of several phenylisopropylamine derivatives. Selegiline was found to be the most active compound.
Selegiline hydrochloride is the compound of the formula C5H5CH2-CH-N-CH2-C=CH. HCI It is used, especially in the (-)-Form in the treatment of Parkinsons disease and as a coronary dilator, hallucinogenic and depressive agent and also as a tranquilliser, analgesic and an appetite suppressant.
The processes for preparing phenylisopropylamine derivatives described in UK 1,153,579 are not generally economically viable.
The present invention is directed towards providing an improved process for the production of phenylisopropylamine derivatives, particularly Selegiline.
According to the invention there is provided a process for preparing a phenylisopropylamine derivative including the steps of:OPEN TO PUBLIC INSPECTION UNDER SECTION 28 AND RULE 23 JNL NoJ.M.:...... $940271 - 2 mixing an appropriate starting material, a solvent and a tertiary amine base, and introducing a propargyl or 2-halogeno-propenyl radical.
In a preferred embodiment of the invention, the tertiary amine base is diisopropylethylamine.
In one embodiment of the invention, the starting material is methamphetamine. Typically, the solvent is toluene.
Preferably, propargylbromide is added and diisopropylethylamine-hydrobromid salt is precipitated.
In one embodiment, the organic layer formed is concentrated and the desired phenylisopropylamine derivative is isolated.
In a particularly preferred embodiment of the invention, the desired phenylisopropylamine derivative is Selegiline. Preferably, HCI is added to form Selegiline HCI.
The invention also provides a phenylisopropylamine derivative, especially Selegiline or Selegiline.HCI whenever prepared by the process of the invention.
The invention will be more clearly understood from the following description thereof given by way of example only.
EXAMPLE 605.4 grs (-) Methamphetamine, 1.7 litres toluene and 1123 mis of diisopropylethylamine were mixed at room temperature. To that clear solution 533.4 mis - S64 0-7 1 - 3 propargylbromide (80% solution in toluene) was added and diisopropylethylamine-hydrobromid salt precipitated. The temperature rose to 59°C. After 6 hours the reaction was completed and 1.5 litres of water were added.
The water layer was separated, the organic layer concentrated under vacuum and Selegiline base was isolated. The base was dissolved in acetone and HCI gas was added until Selegiline HCI was crystallised. After recrystallisation in ethylacetate and methanol 410.5 grs of Selegiline HCI were obtained.
Melting Point: 142.5 - 147°C Optical Rotation: - 11.4° (10% in water) The compound prepared in accordance with the example may be converted into pharmaceutically acceptable acid addition salts. Salt formation may be accomplished by using mineral acids or organic acids.
The process of the invention allows a single pot reaction to be carried out in one phase. A good yield is achieved in a relatively short time. It is believed that the key to such a successful process is the creation of very strong basic conditions using a tertiary amine, especially diisopropylethylamine.
It will be appreciated that while the invention has been described with reference to a process for preparing the particular phenylisopropylamine Selegiline, the process may also be applied to preparing other isopropylamine derivatives .
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.

Claims (5)

1. A process for preparing a phenylisopropylamine derivative, especially Selegiline, including the steps of:5 mixing an appropriate starting material, a solvent and a tertiary amine base, and introducing a propargyl or 2-halogeno-propenyl radical.
2. A process as claimed in claim 1 wherein the tertiary 10 amine base is diisopropylethylamine, preferably the starting material is methamphetamine, preferably the solvent is toluene.
3. A process as claimed in claim 1 or 2 wherein propargylbromide is added and diisopropylethylamine15 hydrobromid salt is precipitated, preferably the organic layer formed is concentrated and the desired phenylisopropylamine derivative is isolated, preferably HCI is added to form Selegiline.HCI.
4. A process substantially as hereinbefore described 20 with reference to the Example.
5. A phenylisopropylamine derivative, especially Selegiline or Selegiline.HCI whenever prepared by a process as claimed in any of claims 1 to 4.
IE027194 1993-12-16 1994-03-29 A process for producing pharmaceutical compounds IES61604B2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
IE027194 IES61604B2 (en) 1993-12-16 1994-03-29 A process for producing pharmaceutical compounds
IE940543A IE940543A1 (en) 1993-12-16 1994-07-04 A process for producing pharmaceutical compounds
GB9413847A GB2284810B (en) 1993-12-16 1994-07-08 A process for producing Selegiline

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IE930972 1993-12-16
IE027194 IES61604B2 (en) 1993-12-16 1994-03-29 A process for producing pharmaceutical compounds

Publications (2)

Publication Number Publication Date
IES940271A2 true IES940271A2 (en) 1994-11-16
IES61604B2 IES61604B2 (en) 1994-11-16

Family

ID=26319672

Family Applications (2)

Application Number Title Priority Date Filing Date
IE027194 IES61604B2 (en) 1993-12-16 1994-03-29 A process for producing pharmaceutical compounds
IE940543A IE940543A1 (en) 1993-12-16 1994-07-04 A process for producing pharmaceutical compounds

Family Applications After (1)

Application Number Title Priority Date Filing Date
IE940543A IE940543A1 (en) 1993-12-16 1994-07-04 A process for producing pharmaceutical compounds

Country Status (2)

Country Link
GB (1) GB2284810B (en)
IE (2) IES61604B2 (en)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1031425A (en) * 1962-03-30 1966-06-02 Chinoin Gyogyszer Es Vegyeszet New aralkylamines and their preparation
DE1802297C3 (en) * 1967-10-25 1974-10-17 Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt, Budapest Isopropylamine derivatives and processes for their preparation
HU187775B (en) * 1982-07-14 1986-02-28 Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt,Hu New process for producing propargile-amines of pharmaceutical activity
HU207282B (en) * 1984-05-31 1993-03-29 Chinoin Gyogyszer Es Vegyeszet Process for producing phenyl-alkyl-amine derivatives and pharmaceutical compositions containing them

Also Published As

Publication number Publication date
IE940543A1 (en) 1995-06-28
GB9413847D0 (en) 1994-08-24
GB2284810B (en) 1998-07-08
IES61604B2 (en) 1994-11-16
GB2284810A (en) 1995-06-21

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Legal Events

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