- MECHANOCHEMICAL SYNTHESIS OF RADIOGRAPHIC AGENTS INTERMEDIATES
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The present invention generally relates to a process using a mechanochemical approach exploiting the mechanical milling of reactants for the manufacturing of acetyl Iopamidol and, more generally, of key intermediates of radiographic contrast agents, and of the contrast agents themselves.
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Page/Page column 26
(2018/06/30)
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- PROCESS FOR THE PREPARATION OF IOPAMIDOL
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The present invention discloses a process for the preparation of Iopamidol of formula (II) and comprising the following steps: a) reacting the Compound (I) wherein X is OR2 or R3, and wherein R2 and R3 are a Ci-C6 linear or branched alkyl, C3-C6 cycloalkyl, C6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N-(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain lopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b). The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.
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- IODINATION PROCESS FOR THE PREPARATION OF 3,5-DISUBSTITUTED-2,4,6-TRIIODO AROMATIC AMINES COMPOUNDS
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The invention discloses a improved process for the preparation of 3,5-disubstituted- 2,4,6-triiodo aromatic amines of formula (II), wherein R1 and R2 are defined as herein. The compounds of formula (II) are the key intermediates for the synthesis of a series of non-ionic contrast agents such as Iopamidol, Iohexol and Iodixanol. The process comprises reacting chlorine-free iodinating reagents with 3,5-disubstituted-2,4,6-triiodo aromatic amines to obtain 3,5-disubstituted-2,4,6-triiodo aromatic amines of formula (II), wherein the molar yield of the iodination reaction can reach to 89%.
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Page/Page column 18
(2013/05/22)
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- Process for the preparation of n,n-substituted 5-amino-1,3-benzenedicarboxamides
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The invention relates to a process for the preparation of a compound of formula (I), wherein R represents a 2,3-dihydroxy-1-propyl or a 1,3-dihydroxy-2-propyl radical, via direct amidation of a dialkyl ester of 5-amino-1,3-benzenedicarboxylic acid of formula (V), wherein R1 represents a straight or branched (C1-C4)-alkyl group, with at least the stoichiometric amount of an amine of formula H2NR.
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- Heterocyclic Nonionic X-ray Contrast Agents. 3. The Synthesis of 5--2,4,6-triiodo-1,3-benzenedicarboxamide Derivatives
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The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2-one moiety, are described.The heterocycle was built from suitably protected 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid derivatives by a three-step procedure consisting of (1) phosgene treatment to obtain the corresponding isocyanates, (2) phenylmercuric chloride-catalyzed addition of glycidol (10) resulting in glycidil carbamates, and (3) pyridine-catalyzed intramolecular N-alkylation, followed by deprotection, to obtain the oxazolidin-2-ones.The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanied by O-alkylation products under the experimental conditions employed.The two carboxamide nitrogen atoms in the intermediates and end products carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues.These highly congested benzenoid compounds exhibited interesting NMR spectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.
- Pillai, K. M. R.,Diamantidis, G.,Duncan, L.,Ranganathan, R. S.
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p. 1344 - 1350
(2007/10/02)
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