- 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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- METHODS FOR PREPARING MOSAPRIDE CITRATE HYDRATE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to a method for preparing a salt hydrate of mosapride and a pharmaceutical formulation comprising the same. The present invention relates to a method for manufacturing a semiconductor device. A pharmaceutical composition for controlled release and a pharmaceutical composition containing the same are provided to have little side effect, little side effect with other drugs or excipients, and have excellent physical properties for use in a pharmaceutical composition containing the controlled release pharmaceutical composition. (by machine translation)
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Paragraph 0121-0145
(2020/10/19)
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- Citric acid mosapride intermediate product and application
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The invention belongs to the field of medical chemistry synthesis, and provides a preparation method of citric acid mosapride intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanaminesalt and citric acid mosapride. The 2-(4-fluorobenzoamido)ethanol and 1H-Isoindole-1,3(2H)-dione,2-(2-oxiranylmethyl) are taken as raw materials, and the intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanamine salt is obtained after acid treating is conducted; the intermediate product IV and an intermediate V 2-oxethyl-4-acetamido-5-Chlorobenzoic acid ethyl ester compounds aretaken as raw materials, dichloromethane is taken as a solvent, and EDCI and DMAP are taken as catalysts to prepare mosapride salt; the mosapride salt is reacted with citric acid aqueous solution to prepare citric acid mosapride. The intermediate product has the advantages that products are high in yield, raw materials are easy to obtain, the production cost is low, and the intermediate product issuitable for industrialized 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 0065; 0069; 0071
(2016/10/08)
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- HIGHLY PURE MOSAPRIDE CITRATE DIHYDRATE AND PROCESSES FOR ITS PREPARATION
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The present invention provides for highly pure mosapride citrate dihydrate and processes for its preparation. The present invention further provides a process for the preparation of mosapride citrate dihydrate substantially free of impurity D-II.
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Page/Page column 11
(2011/10/03)
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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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- Absorption, distribution and excretion of [carbonyl-14C]-mosapride citrate after a single oral administration in rats, dogs and monkeys
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Absorption, distribution and excretion of mosapride citrate ((±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]m ethyl] benzamide citrate, AS-4370, CAS 112885-42-4), a novel gastric prokinetic drug, were studied with 14C-labeled drug in male and female rats mainly after a single oral administration. Plasma concentrations and excretion following oral administration of [14C]mosapride were also investigated in dogs and monkerys of both sexes. The main experimental dose was 10 mg/kg. After oral administration, [14C]mosapride radioactivity was rapidly absorbed through the intestinal tract. In male rats, concentration of plasma radioactivity reached the maximum (C(max); 1410 ng eq./ml) 1 h after administration and decreased biphasically with halflives of about 2 h in α-phase (t( 1/2 )α) and in β-phase (t( 1/2 )β) of about 8 h. t( 1/2 )β was virtually constant in the dose range from 1 mg/kg to 100 mg/kg, and the area under the plasma concentration-time curve (AUC) was proporticnal to the dose. In female rats, biphasic plasma concentration-time profile with similar half-lives was also observed, but C(max) (2070 ng eq./ml) and AUC were larger than those in male rats, suggesting the sex difference in pharmacokinetics. In dogs and monkeys, C(max)s of plasma concentration were about 1000 ng eq./ml and 2000-3000 ng eq./ml, respectively and sex difference was not observed. Plasma concentrations declined in a biphasic manner and t( 1/2 )α and t( 1/2 )β were about 4 h and 15 h in dogs and about 3 h and 10 h in monkeys, respectively. The [14C]mosapride radioactivity was distributed to many tissues including the stomach and small intestine at the higher concentration, while to the brain and eye ball at the lower concentration than the plasma in male rats. Radioactivities in most tissues decreased essentially in parallel with those in plasma. In pregnant rats, concentrations of radioactivity in fetus were a little higher than those in the maternal plasma. In lactating rats, milk radioactivity concentrations were about 5 times higher than corresponding plasma concentrations, and both of them decreased with similar half-lives. Mosapride was bound to serum protein of various animal species, albumin and α1-acid glycoprotein, in about 93-99%. After oral administration in rats, about 40% of dosed radioactivity was excreted into urine and about 60% into feces via bile. Neither dose dependency nor sex differences was observed in excretion. In dogs, about 20% of dosed radioactivity was recovered in urine and about 70% in feces. In monkeys, recoveries in urine and feces were about 60 and 30% of dose, respectively.
- Matsumoto,Tagawa,Amejima,Nakao,Kagemoto,Fujii,Miyazaki,Sekine
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p. 1084 - 1094
(2007/10/02)
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