Claims
- 1. A process for the preparation of S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide, said process comprising forming S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-acetyloxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide from S-(−)-5-[[2-(acetyloxy)-1-oxopropyl]-amino]-2,4,6-triiodo-1,3-benzendicarboxylic acid di-chloride and 2-amino-1,3-propanediol in a solvent selected from the group consisting of a lower alcohol or monoalkyl ether glycol.
- 2. A process for the preparation of S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide, said process comprising forming S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-acetyloxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide from S-(−)-5-[[2-(acetyloxy)-1-oxopropyl]-amino]-2,4,6-triiodo-1,3-benzendicarboxylic acid di-chloride and 2-amino-1,3-propanediol in a solvent selected from the group consisting of a lower alcohol or monoalkyl ether glycol,wherein the minimum molar ratio of 2-amino-1,3-propanediol to S-(−)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzendicarboxylic acid dichloride ranges from 6 to 25.
- 3. A process for the preparation of S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide, said process comprising forming S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-acetyloxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide from S-(−)-5-[[2-(acetyloxy)-1-oxopropyl]-amino]-2,4,6-triiodo-1,3-benzendicarboxylic acid di-chloride and 2-amino-1,3-propanediol in a solvent selected from the group consisting of a lower alcohol or monoalkyl ether glycol,wherein the minimum molar ratio of 2-amino-1,3-propanediol to S-(−)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzendicarboxylic acid dichloride ranges from 8 to 15.
- 4. The process according to claim 1, 2 or 3, in which the solvent is a straight or branched C2-C5 alcohol.
- 5. The process according to claim 1, 2 or 3, in which the solvent is selected from the group consisting of C2-C5 secondary alcohols.
- 6. The process as claimed in claim 5, in which the solvent is selected from the group consisting of: isopropanol, sec-butanol and t-butanol.
- 7. The process according to claim 1, 2 or 3, in which the solvent is a C3-C7 glycol monoalkyl ether.
- 8. The process as claimed in claim 7, in which the solvent is selected from 2-methoxyethanol and 2-ethoxyethanol.
- 9. The process according to claim 1, 2 or 3, in which the reaction temperature for the preparation of S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-acetyloxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide ranges from 48 to 85° C. and the reaction time ranges from 2 to 6 hours.
- 10. The process according to claim 1, 2, or 3, including an additional step at the end of the reaction between 2-amino-1,3-propanediol and S-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-acetyloxy-1-oxopropyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamide, of distilling off the solvent to dryness under pressure, hydrolyzing the acetate group by addition of water and heating the solution to 50-70° C., wherein the temperature is maintained for a time from 4 to 8 hours; thereafter neutralizing the solution by addition of hydrochloric acid, then concentrated and purified by elution on a macroporous highly cross-linked styrene resin and subsequently on a strong sulfonic type cationic resin, regenerated in the acidic form, and on a secondary amine-type mean anionic resin, regenerated in the OH− form.
- 11. The process as claimed in claim 10, in which the acetate group is hydrolyzed at a temperature ranging from 55 to 65° C. for a time from 5 to 7 hours.
Parent Case Info
This application claims priority of Ser. No. 60/084,735 the disclosure of which is hereby incorporated by reference.
US Referenced Citations (5)
Foreign Referenced Citations (2)
Number |
Date |
Country |
2 272 218 |
Nov 1994 |
GB |
1 472 050 |
Apr 1997 |
GB |
Provisional Applications (1)
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Number |
Date |
Country |
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60/084735 |
May 1998 |
US |