Process for the preparation of iosimenol
View Patent ↗A process for the preparation of iosimenol comprising reacting 5,5′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (C-VI) with a 3-halo-1,2-propanediol in an aqueous solvent. A process for the preparation of C-VI comprising reacting 3,3′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) with 3-amino-1,2-propanediol in the presence of an inorganic base and a suitable non-aqueous polar solvent. A process for the preparation of C-V comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof.
1. A process for the preparation of 3,3′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof, wherein C-V and C-IV have the formulae:
2. The process of claim 1 wherein the solvent further comprises a suitable ethereal solvent.
3. The process of claim 1 wherein the solvent is selected from acetonitrile, ethyl acetate, a mixture of acetonitrile and tetrahydrofuran, a mixture of ethyl acetate and tetrahydrofuran, a mixture of acetonitrile and 1,2-dimethoxyethane, a mixture of ethyl acetate and 1,2-dimethoxyethane, or a mixture of acetonitrile and ethyl acetate.
4. The process of claim 3 wherein the solvent is selected from acetonitrile, ethyl acetate, a mixture of acetonitrile and tetrahydrofuran, a mixture of ethyl acetate and tetrahydrofuran, or a mixture of acetonitrile and ethyl acetate.
5. The process of claim 4 wherein the solvent comprises acetonitrile or a mixture of acetonitrile and tetrahydrofuran.
6. The process of claim 5 wherein the solvent is a mixture of acetonitrile and tetrahydrofuran wherein the weight ratio of acetonitrile:tetrahydrofuran is about 1:9 to about 49:1.
7. The process of claim 6 wherein the weight ratio of acetonitrile:tetrahydrofuran is about 1:1 to about 49:1.
8. The process of claim 4 wherein the solvent is ethyl acetate or a mixture of ethyl acetate and tetrahydrofuran.
9. The process of claim 8 wherein the solvent is a mixture of ethyl acetate and tetrahydrofuran wherein the weight ratio of ethyl acetate:tetrahydrofuran is about 1:9 to about 49:1.
10. The process of claim 9 wherein the weight ratio of ethyl acetate:tetrahydrofuran is about 1:1 to about 49:1.
11. The process of claim 1 wherein compound C-V is formed as a particulate precipitate in the solvent system, and wherein the compound C-V particles have a particle size larger than compound C-V particles prepared in a solvent system comprising only ethereal solvents.
12. The process of claim 7 wherein the weight ratio of acetonitrile:tetrahydrofuran is about 3:1 to about 9:1.
13. The process of claim 10 wherein the weight ratio of ethyl acetate:tetrahydrofuran is about 3:1 to about 9:1.
14. The process of claim 5 further comprising isolating particles of compound C-V by filtration, wherein the rate of filtration is greater than the rate of filtration for compound C-V prepared in a solvent system comprising only ethereal solvents.
15. The process of claim 14 wherein the weight ratio of acetonitrile:tetrahydrofuran is about 9:1 or greater.
16. The process of claim 8 further comprising isolating particles of compound C-V by filtration, wherein the rate of filtration is greater than the rate of filtration for compound C-V prepared in a solvent system comprising only ethereal solvents.