112914-13-3

Usage

Chemical Properties

Clear Pale Yellow Oil

Uses

Mosapride intermediate.

InChI:InChI=1/C12H17FN2O/c13-11-3-1-10(2-4-11)8-15-5-6-16-12(7-14)9-15/h1-4,12H,5-9,14H2

Upstream product

• 112913-94-7 2-<(acetylamino)methyl>-4-(4-fluorobenzyl)morpholine 
• 5455-98-1 2-oxiranylmethylisoindole-1,3-dione 
• 22116-33-2 2-(4-fluoro-benzyl-amino)-ethanol 
• 636582-78-0 2-[4-(4-fluoro-benzyl)-morpholine-2-yl-methyl]-isoindole-1,3-dion 
• 352-11-4 1-chloromethyl-4-fluorobenzene 
• 459-57-4 4-fluorobenzaldehyde 
• 131322-23-1 <2-(acetylamino)methyl>morpholine acetyl salt 
• 112913-96-9 2-(N-acetylaminomethyl)-4-benzylmorpholine 

Downstream Products

• 112913-94-7 2-<(acetylamino)methyl>-4-(4-fluorobenzyl)morpholine 
• 182067-91-0 2-benzyloxycarbonylaminomethyl-4-(4-fluorobenzyl)morpholine 
• 174458-41-4 1-[4-(p-fluorobenzyl)-2-morpholinylmethyl]-3-methylurea 
• 1420999-21-8 2-[(1-benzylpiperidin-4-yl)amino]-N-{[4-(4-fluorobenzyl)morpholin-2-yl]methyl}nicotinamide 
• 112885-34-4 4-acetylamino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide 
• 112885-42-4 mosapride citrate 
• 112885-41-3 mosapride 

Relevant academic research and scientific papers

Citric acid mosapride intermediate product and application

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.

Method for preparing mosapride citrate intermediate

The invention belongs to the technical field of medicines and particularly relates to a method for preparing a mosapride citrate intermediate IV 4-(4-fluorophenyl)-2-aminomethyl morpholine. The methodcomprises the following steps: phthalimide potassium salt and dichloro-2-propanol react to produce an intermediate II N-(2-hydroxy-3-chloropropyl) phthalimide, then the produced intermediate II and an intermediate I 2-(4-fluorphenylamine)ethyl alcohol are condensed to prepare an intermediate III N-3-[4-fluorophenyl-2-(hydroxy-ethylamine)-2-hydroxypropyl]phthalic diamide, and the intermediate IIIis subjected to cyclization and hydrolysis to obtain the intermediate IV 4-(4-fluorophenyl)-2-aminomethyl morpholine. The method is short in route, lower in production cost and suitable for industrialproduction.

PROCESS FOR THE SYNTHESIS OF A BENZAMIDE DERIVATIVE

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.

Pyrimidine derivatives

Pyrimidine derivatives useful as a gastrointestinal prokinetic agent, represented by formula STR1 wherein X is O or NR5, Y is O, S or NR5 wherein R5 is a hydrogen atom, a C1 -C6 alkyl group or the like; R1 and R2 may be the same or different and each is a hydrogen atom, a C1 -C6 alkyl group or the like; R3 is CN, or COOR6 wherein R6 is a C1 -C6 alkyl group, a C3 -C6 cycloalkyl group, an aryl group or the like; R4 is --SR7 or --NR8 R9 wherein R7 is a C1 -C6 alkyl group; R8 is a C1 -C6 alkyl group or the like; R9 is a hydrogen atom, a C1 -C6 alkyl group or the like, or R8 and R9 may represent, together with the nitrogen atom to which they are attached, an N-substituted piperazine ring of formula (X) STR2 wherein R10 represents a C1 -C6 alkyl group or the like or a pharmacologically acceptable salt thereof. The above-mentioned compounds are useful as a gastrointestinal prokinetic agent used for the therapy of digestive tract diseases.

Synthesis and biological activity of 4-amino-5-chloro-2-ethoxy-3- hydroxybenzamides, metabolites of a new gastroprokinetic agent, mosapride

To confirm the proposed structures of the minor metabolites of a potential gastroprokinetic agent, mosapride, 4-amino-5-chloro-2-ethoxy-3- hydroxy-N-(2-morpholinylmethyl)benzamide (3) and the N-(5-oxo-2- morpholinyl)methyl analogue 4 were prepared. As the

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

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.

Substituted benzamide derivatives, for enhancing gastrointestinal motility

Compounds of the formula: STR1 wherein R is hydrogen, alkoxycarbonyl, benzyloxycarbonyl, heteroarylalkyl, phenylalkenyl, or --T--(Y)p --R6 (wherein T is single bond or alkylene, Y is oxygen, sulfur or carbonyl, R6 is phenyl, substituted phenyl, naphthyl, or diphenylmethyl, and p is 0 or 1, provided that when T is single bond, p is 0); R1 is halogen, hydroxy, alkoxy, cycloalkyloxy, alkenyloxy, alkynyloxy, alkoxy interrupted by oxygen or carbonyl, alkylthio, amino, monosubstituted amino, or a substituted alkoxy; R2 is hydrogen; R3 is hydrogen, halogen, amino, alkylamino, dialkylamino, alkanoylamino, or nitro; R4 is hydrogen, halogen, nitro, sulfamoyl, alkylsulfamoyl, or dialkylsulfamoyl; or any two adjacent groups of the R1, R2, R3 and R4 may combine to form alkylenedioxy, and the remaining two groups are each hydrogen; R5 is hydrogen or alkyl; X is alkylene; m and n are each 1 or 2; provided that at least one of the groups R2, R3 and R4 is other than hydrogen, and acid addition salts, quaternary ammonium salts and N-oxide derivatives thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds, salts and N-oxide derivatives thereof show excellent gastrointestinal motility enhancing activity.