- Novel preparation method of mosapride
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The invention discloses a novel preparation method of mosapride.Cheap 2-chlorotoluene is used as an initial raw material is subjected to nitration, nucleophilic substitution, free radical bromination, chlorination, alkylation, nitro reduction and oxidative amidation to synthesize mosapride. According to the scheme, raw materials are easy to obtain, dangerous processes and highly toxic reagents are avoided, the method is green and environment-friendly, oxidation amidation is adopted, selectivity is achieved, formation of aromatic amide by-products is avoided, and the yield is high.
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- Synthesis method of mosapride citrate
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The invention provides a preparation method of mosapride citrate, namely 4-amino-5-chloro-2-ethoxy-N-((4-(4-fluorophenyl)morpholin-2-yl)methyl)benzamide citrate. The method provided by the invention has the advantages of cheap and easily available raw materials, short reaction steps, high yield, simple post-treatment and the like, reduces the cost, has certain technical advantages, and is suitablefor large-scale industrial production.
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- 4-amino-5-chloro-2-ethoxy-N- "[ 4-(4-Flurobenzyl)-2-morphorinyl] methyl" phenylbenzamide hydroxycitric salt 2 hydrate production method
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PROBLEM TO BE SOLVED: To provide a method for producing a high-purity 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citric acid salt dehydrate, which produces less by-product. SOLUTION: The method for producing a 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citric acid salt dehydrate includes reacting 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide and citric acid at ≥30°C and ≤70°C in a mixed solvent of water and a water-soluble organic solvent. COPYRIGHT: (C)2012,JPOandINPIT
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Paragraph 0062-0064
(2016/10/08)
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- DRY-COATED ORALLY-DISINTEGRATING TABLET
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The purpose of the present invention is to provide a press-coated orally-disintegrating tablet characterized by containing an inner core which has an excellent disintegratability in oral cavity and a suitable hardness as a whole tablet. The present invent
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- DRY-COATED ORALLY-DISINTEGRATING TABLET
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The purpose of the present invention is to provide a press-coated orally-disintegrating tablet characterized by containing an inner core which has an excellent disintegratability in oral cavity and a suitable hardness as a whole tablet. The present invent
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- PROCESS FOR THE SYNTHESIS OF A BENZAMIDE DERIVATIVE
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The invention relates to a process for the synthesis of mosapride citrate of formula (I), the chemical name: (R,S)-4-amino-5-chloro-2-ethoxy-N-{ [4-(4-fluoro-benzyl)-2- morpholinyl]-methyl}benzamide citrate dihydrate, (I), (II) reacting the compound of formula (II) with di-tert-butyl-dicarbonate in an alcohol in the presence of a base, the obtained product is ethylated in an inert solvent in the presence of a base, the obtained compound is hydrolyzed with an alkyl-hydroxide and the obtained salt neutralized with an acid, the obtained product is chlorinated, and the obtained compound of formula (VI) is reacted with the compound of formula (VII), (VI), (VII) where BOC is tert-butoxy-carbonyl protecting group and removing the protecting group from the obtained compound of formula (VIII) the mosapride base is prepared, (VIII) where BOC is defined as above and in desired case with an acid, preferably with citric acid a pharmaceutically acceptable salt, preferably the mosapride citrate dehydrate of formula (I) is produced.
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- Novel benzamides as selective and potent gastrokinetic agents. 2.1 Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl] benzamide citrate (AS-4370) and related compounds
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The title compounds (19-55) with a 4-substituted 2-(aminomethyl)morpholine group were prepared and evaluated for the gastrokinetic activity by determining their effect on gastric emptying of phenol red semisolid meal in rats. Introduction of chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl] methyl]benzamide (23b) showed the most potent gastric emptying activity (effects on phenol red semisolid meal in rats and mice, and on resin pellets solid meal in rats). The gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that of cisapride and was higher than that of metoclopramide. In contrast to metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.
- Kato,Morie,Kon,Yoshida,Karasawa,Matsumoto
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p. 616 - 624
(2007/10/02)
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