Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-01-26
2002-03-05
Aulakh, Charanjit S. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S334000, C546S336000
Reexamination Certificate
active
06353108
ABSTRACT:
This application is a 371 of PCT/FR99/01649 filed Jul. 8, 1999.
The present invention relates to a process for the preparation of 4-(3-pyridinyl)-1H-imidazole, of certain of its derivatives as well as the intermediate products used.
A subject of the invention is a process for the preparation of compounds of formula (I)
in which R represents a hydrogen atom or an alkyl radical containing up to 8 carbon atoms characterized in that a compound of formula (II)
in which alk represents the remainder of an alkyl radical containing up to 4 carbon atoms is subjected to the action of a compound of formula (III)
RCONH
2
(III)
in which R retains its previous meaning, in order to obtain the compound of formula (IV)
in which R retains its previous meaning which is subjected to a cyclization in order to obtain the sought product of formula (I).
When R represents an alkyl radical, it is for example the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tertbutyl radical.
Alk represents for example a methyl, ethyl or n-propyl radical.
In a preferred embodiment, the reaction between the compounds (II) and (III) takes place in a mixture of alcohol and formamide. As alcohol there can be mentioned methanol, ethanol or propanol.
The cyclization of the compound of formula (IV) takes place in formamide.
A more particular subject of the invention is the preparation of the compound of formula (I) in which R is a hydrogen atom.
A more particular subject of the invention is a process characterized in that alk represents a methyl radical.
The cyclization preferably takes place by heating.
4-(3-pyridinyl)-1H imidazole is a known product described for example in J. Chem.-Soc.-753-5 1938 which can be used for preparing pharmaceutical products (cf. EP 680967).
A subject of the invention is also a process characterized in that the product of formula (II) is prepared by the action of an alcohol and of an alkaline alcoholate, alk
1
OH/alk
2
OM, alk
1
and alk
2
, identical or different, representing an alkyl radical containing up to 4 carbon atoms and M representing a sodium or potassium atom on a compound of formula (A),
OM representing a hydroxyl radical blocked, in the form of a good parting group in order to obtain 3-(2H-azirin-3-yl) pyridine
which is subjected to the action of an acid in the presence of an alcohol alkOH, alk retaining the same meaning as previously in order to obtain the corresponding compound of formula (II)
The oxime is protected for example in the form of mesylate or tosylate, the alcohol and the alkaline alcoholate are for example methanol and sodium methylate, ethanol and sodium ethylate, butanol and sodium terbutylate.
The acid used can be oxalic acid, formic acid or also hydrochloric or sulphuric acid.
In a preferred embodiment:
M is a tosyl radical
methanol is used in the presence of sodium methylate
the acid is oxalic acid.
A more particular subject of the invention is a process in which alk, alk
1
and alk
2
represent the same alkyl radical for example the methyl radical.
A more particular subject of the invention is a process in which the intermediate product 3-(2H-azirin-3-yl)-pyridine is not isolated.
A more particular subject of the invention is a process characterized in that 1-(3-pyridinyl)-ethanone O-[(4-methylphenyl) sulphonyl] oxime is subjected to the action of methanol and sodium methylate in order to obtain 3-(2H-azirin-3-yl)-pyridine which is subjected to the action of oxalic acid in order to obtain &bgr;,&bgr;-dimethoxy-2-(3-pyridinyl)ethyl)-amine which is subjected to the action of formamide in order to obtain N-[&bgr;,&bgr;-dimethoxy-2-(3-pyridinyl)ethyl]-formamide which is subjected to a cyclization in order to obtain the sought product.
A quite particular subject of the invention is a process in which the intermediate products used are not isolated.
The compounds of formula (II) with the exception of &bgr;,&bgr;-diethoxy-3-pyridine ethanamine described in Org. Synth. (1986) 64, 1926 are new products and are in themselves a subject of the present invention.
The compounds of formula (IV) are new and are in themselves a subject of the present invention.
A more particular subject of the invention is the compounds of formula (II) and (IV) described in the experimental part namely:
&bgr;,&bgr;-dimethoxy-3-pyridine ethanamine and N-[&bgr;,&bgr;-dimethoxy-2-(3-pyridinyl)ethyl]-formamide.
The following examples illustrate the invention without however limiting it.
Preparation: &bgr;,&bgr;-dimethoxy-3-pyridine ethanamine
Stage A: 3-[2H-azirin-3-yl)-pyridine
100 g of 1-(3-pyridinyl)-ethanone O-[(4-methylphenyl)sulphonyl]-oxime is introduced at 20° C. under a nitrogen atmosphere into a solution containing 400 ml of anhydrous methanol and 23.45 g of sodium methylate. Agitation is carried out for 2 hours at 20~22° C. and a suspension containing the sought product is obtained.
Stage B: &bgr;,&bgr;-dimethoxy-3pyridine ethanamine
The suspension obtained previously is cooled down to 0° C. and 31.03 g of oxalic acid is added. Agitation is carried out for 15 minutes at 0°/+5° C. A suspension is obtained which is used as it is in Example 1. After isolation and purification, &bgr;,&bgr;-dimethoxy-3-pyridine ethanamine is obtained.
NMR CDCl
3
ppm
1.03(broad m) assumed mobile NH
2
3.02(s)
3.22(s) 6H 2 OCH
3
7.33(bdd, J=5 and 9) H
5
7.80(dt, J=9 and 2) H
4
8.59(dd, J32 5 and 2) H
6
8.73(dd, J=2 and 1) H
2
REFERENCES:
patent: 4302464 (1981-11-01), La Mattina et al.
patent: 1259360 (1961-03-01), None
patent: 02145572 (1990-06-01), None
La Mattina et al “Use of . . . Acetals”, Synthesis, No. 4, 1980 pp. 329-330.
Bouchet Raphael
Lagouardat Jacques
Scholl Jacques
Aulakh Charanjit S.
Aventis Pharma S.A.
Bierman, Muserlian and Lucas
LandOfFree
Method for preparing 4-(3-pyridinyl)-1h-imidazole and the... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preparing 4-(3-pyridinyl)-1h-imidazole and the..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preparing 4-(3-pyridinyl)-1h-imidazole and the... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2871588