Chloroacetyl chloride → 5-(2-Chloroacetamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

HRID 1358850Notes

Reaction equation

HRID 1358850 reaction equation
[NH2:1][C:2]1[C:3]([I:26])=[C:4]([C:18]([NH:20][CH2:21][CH:22]([OH:25])[CH2:23][OH:24])=[O:19])[C:5]([I:17])=[C:6]([C:15]=1[I:16])[C:7]([NH:9][CH2:10][CH:11]([OH:14])[CH2:12][OH:13])=[O:8].CN(C)C(=O)C.[Cl:33][CH2:34][C:35](Cl)=[O:36].[OH-].[Na+]>O>[OH:25][CH:22]([CH2:23][OH:24])[CH2:21][NH:20][C:18](=[O:19])[C:4]1[C:3]([I:26])=[C:2]([NH:1][C:35](=[O:36])[CH2:34][Cl:33])[C:15]([I:16])=[C:6]([C:7]([NH:9][CH2:10][CH:11]([OH:14])[CH2:12][OH:13])=[O:8])[C:5]=1[I:17]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 14798Sodium HydroxideHCID 31374DimethylacetamideHCID 103950115-Amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Product 1

HCID 111047205-(2-Chloroacetamido)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The general procedure for the process of the invention involves reacting 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide with N,N-dimethylacetamide and chloroacetyl chloride. The resulting product is hydrolyzed with a base (such as sodium hydroxide). A homogeneous solution is obtained by adding water. Precipitation is affected to yield N,N′-bis(2,3-dihydroxypropyl)-5-(2-chloroacetamido)-2,4,6-triiodoisophthalamide. Alternately, 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide is reacted with N,N-dimethylacetamide, acetonitrile, and chloroacetyl chloride. The resulting product is hydrolyzed with a base. A homogeneous solution is obtained by adding water. Precipitation is affected to yield N,N′-bis(2,3-dihydroxypropyl)-5-(2-chloroacetamido)-2,4,6-triiodoisophthalamide. This product is combined with an aqueous base and deionized water. 2-Chloroethanol is added followed by heating. The addition of hydrochloric acid yields N,N′-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)(2-chloroacetamido)]-2,4,6-triiodoisophthalamide. Alternately, N,N′-bis(2,3-dihydroxypropyl)-5-(2-chloroacetamido)-2,4,6-triiodoisophthalamide plus metal halide and deionized water are combined. Ethylene oxide is added followed by heating. The addition of hydrochloric acid yields N,N′-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)(2-chloroacetamido)]-2,4,6-triiodoisophthalamide. This product is suspended in water with acetate ions and hydrochloric acid added. This suspended solution can take place at or above atmospheric pressure. Generally about 1 to about 2 atmospheres above atmospheric pressure is used. After adding aqueous sodium hydroxide to, maintain the pH, the reaction yields N,N′-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxyethyl)glycolamido-2,4,6-triiodoisopthalamide. Finally, salts and low molecular weight impurities are removed.

Workup

  1. customA homogeneous solution is obtained
  2. customPrecipitation

Sources & evidence

ORD record
ord-385e341cc24a44bc95afca4960b143ea
Source dataset
uspto-grants-2003_07
Patent number
US06596904B1

Reaction notes

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