Process for the preparation of amphiphilic imidazolinium compounds
AssigneeBayer Animal Health GmbH
InventorsMarco Brünjes, Mark James Ford
Life of this patent
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Abstract
The present invention generally relates to improved processes for the preparation of amphiphilic imidazolinium compounds such as 1-[2-(9(Z)-octadecenoyloxy)ethyl]-2-(8(Z)-heptadecenyl)-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM). In particular, the invention relates to processes for the synthesis of such compounds that avoid the need for toxic reagents, are more economical, and result in less waste than conventional methods. DOTIM and similar compounds can be formulated as cationic liposomes, which are useful as chemical vectors for nucleic acid delivery in gene therapy.
Claims25
A process for preparing a compound of Formula (I)
- wherein R is a straight-chain, aliphatic, saturated or unsaturated hydrocarbyl group of 11 to 29 carbon atoms, the process comprising:
- reacting a compound of Formula (II) with a hydrogen halide (HX) to provide a compound of Formula (III), wherein X is Cl, Br, or I;
- reacting the compound of Formula (III) with a carboxylic acid halide [RC(O)Y], wherein R is as defined above for formula (I) and wherein Y is selected from the group consisting of Cl, Br, F, and I, or a carboxylic acid anhydride [RC(O)OC(O)R2], wherein R is as defined above for Formula (I) and R2 is a straight-chain or branched, aliphatic, saturated or unsaturated hydrocarbyl group of 1 to 29 carbon atoms, to provide a compound of Formula (IV);
- and
- heating the compound of Formula (IV) to provide a compound of Formula (I)
A process for preparing a compound of Formula (I)
- wherein R is a straight-chain, aliphatic, saturated or unsaturated hydrocarbyl group of 11 to 29 carbon atoms, the process comprising:
- heating a compound of Formula (IV) in a reaction mixture comprising an organic solvent and a base to provide the compound of Formula (I)
- wherein R is as defined above for Formula (I) and X is Cl, Br, or I.
Dependencies are inferred from the claim text.