Process for the preparation of substituted thiopyran-1-oxides

Details Process for the preparation of substituted thiopyran-1-oxides Process for the preparation of substituted thiopyran-1-oxides

1996-04-24

1997-11-18

Ivy, C. Warren

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546341, 435118, 435122, C07D40904

Patent

active

056889542

DESCRIPTION:

BRIEF SUMMARY
This application is a 35 USC 371 National Stage filing of PCT/G894/02332 published as WO95/11900 on May 4, 1995.
This invention relates to a process for the preparation of intermediates useful in the preparation of (1R,2R)-2-(3-pyridyl)-N-alkyl-tetrahydro-2H-thiopyran-2-carbothioamide 1-oxides, which possess useful pharmaceutical properties, for example anti-hypertensive properties, and to intermediates and pharmaceutical products prepared using said process.
In the specifications of European Patent No. 0097584 and its equivalent U.S. Pat. No. 4,568,682 there are described compounds of general formula I, hereinafter depicted, wherein R represents a hydrogen atom or an alkyl group containing 1 to 4 carbon atoms, Het represents an aromatic heterocyclic radical and Y represents a bond or a methylene linkage.
The presence of two asymmetric centres leads to 4 diastereoisomers which may be separated into two racemic pairs of enantiomers which can be designated as "form A" (or the more polar product) and "form B" (or the less polar product), the relative polarity being determined by thin layer chromatography. Each of these two forms may be resolved, into its two enantiomers.
Among the compounds of formula I, form A of 2-(3-pyridyl)-N-methyltetrahydro-2H-thiopyran-2-carbothioamide 1-oxide consists of a mixture of trans-isomers which may be represented by formulae II and III, hereinafter depicted.
Studies carried out on isomers II and III have shown that the more active form is isomer III, whose absolute configuration is 1R,2R.
In the specifications of European Patent Application Publication No. 0426557 and its equivalent U.S. Pat. No. 5,120,852 there is described a process for the preparation of compounds of general formula IV, hereinafter depicted, wherein R.sup.1 represents a straight- or branched-chain alkyl group containing 1 to 4 carbon atoms by the action of an alkyl isothiocyanate of the general formula: sulphoxide of formula VI or VII, hereinafter depicted, or on the anions derived from mixtures thereof.
According to the specifications of the aforementioned European Patent Application Publication No. 0426557 and U.S. Pat. No. 5,120,852, the compounds of formulae VI and VII may be prepared by the selective oxidation, by chemical or biochemical means, of the compounds of formula VIII, hereinafter depicted, which generally occur in the racemic form.
(1R,2S)-2-(3-pyridyl)tetrahydro-2H-thiopyran 1-oxide of formula VII is prepared by the diastereoselective oxidation of (S)-2-(3-pyridyl)tetrahydro-2H-thiopyran of formula IX, hereinafter depicted, which, according to a first feature of the present invention, is prepared by the cyclisation of compounds of the general formula XII hereinafter depicted, wherein R.sup.2 represents a straight or branched C.sub.1-4 alkyl group, preferably methyl and R.sup.3 represents an alkyl-or arylsulphonyl group, eg a methanesulphonyl group, which, according to a further feature of the present invention, are prepared from compounds of formula X, which, according to another feature of the present invention are prepared by the stereoselective reduction, by chemical or biochemical means, of compounds of general formula XI, hereinafter depicted, wherein R.sup.2 is as hereinbefore defined, or a salt or an addition compound thereof.
The preparation of (1R,2S)-2-(3-pyridyl)-tetrahydro-2H-thiopyran 1-oxide of formula VII, by the oxidation of (S)-2-(3-pyridyl)-tetrahydro-2H-thiopyran of formula IX, is carried out, for example, by means of a hypochlorite, such as sodium hypochlorite or by means of an organic hydroperoxide, e.g. peracetic acid or alpha,alpha-dimethylbenzyl hydroperoxide, or, more especially, by means of hydrogen peroxide, preferably in the presence of a catalyst such as a metal, for example zinc or a transition metal, e.g. cobalt, molybdenum, iron, vanadium or titanium or, more especially, copper, or a compound thereof, for example an acetylacetonate thereof.
The enantiomeric purity, i.e. the enantiomeric excess, of the (1R,2S)-2-(3-pyridyl)tetrahydro-2H-thiopyran 1-oxide of fo

REFERENCES:
patent: 5120852 (1992-06-01), Aloup et al.

Affiliated with

Also associated with

Rating

Process for the preparation of substituted thiopyran-1-oxides does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of substituted thiopyran-1-oxides, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of substituted thiopyran-1-oxides will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1566953