- Process for efficiently synthesizing Cetilistat by taking 2-amino-5-methyl benzoic acid as raw material
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The invention discloses a process for efficiently synthesizing Cetilistat by taking 2-amino-5-methyl benzoic acid as a raw material. The process comprises the steps: taking 2-amino-5-methyl benzoic acid as a raw material, and carrying out transesterification on 2-amino-5-methyl benzoic acid and triphosgene under the action of organic base catalysis to generate an intermediate c, namely 6-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione; carrying out a reaction on sulfonyl chloride (d) with a specific structure with n-hexadecanol under the condition of base catalysis to generate an intermediatef; and finally, carrying out an alkylation reaction on oxygen atoms of the intermediate c and the intermediate f in the presence of organic base to generate the target product Cetilistat. According tothe method, the reaction steps for synthesizing the Cetilistat are few, the process route is short, side reactions are few, the yield of the final product is high, and the purity is more than 99%.
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Paragraph 0053; 0058-0059; 0064; 0068-0070
(2020/04/02)
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- NOVEL PROCESSES FOR THE PREPARATION OF 2-OXY-BENZOXAZINONE DERIVATIVES
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Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of 2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one, and its intermediates, in high yield and purity.
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- A west for favorable department his preparation method
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The invention discloses a preparation method of cetilistat, which has the advantages of high yield, mild reaction conditions and the like and can easily implement industrial production. The method comprises the following steps: (1) reacting methyl 2-amino-5-halobenzoate with triphosgene to obtain 2-methoxycarbonyl-4-halophenylisocyanate; adding hexadecanol to generate methyl 2-(hexadecaalkoxycarbonylamino)-5-halobenzoate; (2) adding the methyl 2-(hexadecaalkoxycarbonylamino)-5-halobenzoate, methyl boron dihydroxide and alkali into water and an organic solvent, adding a palladium catalyst, and reacting to obtain methyl 2-(hexadecaalkoxycarbonylamino)-5-methylbenzoate; (3) carrying out esterolysis reaction on the methyl 2-(hexadecaalkoxycarbonylamino)-5-methylbenzoate to obtain 2-(hexadecaalkoxycarbonyl)-5-methylbenzoic acid; (4) suspending the 2-(hexadecaalkoxycarbonyl)-5-methylbenzoic acid in pyridine, and cyclizing under the action of a dehydrating agent; and purifying and carrying out crystal transformation to obtain the cetilistat.
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Paragraph 0063; 0064; 0065
(2017/08/25)
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- Method of preparing Cetilistat through one-pot method
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The invention discloses a method of preparing Cetilistat through a one-pot method. The method comprises the following steps that 2-amino-5-toluic acid is sequentially reacted with cetyl chloroformate and methane sulfonyl chloride in a mixed solution, and the Cetilistat is obtained through the one-pot method. According to the method, with selection of a mixed solution system as a reaction medium and the methane sulfonyl chloride as a lactonization reagent and adoption of the one-pot method to prepare the Cetilistat, an obtained product is high in yield and purity; the process is simple and not tedious, separation and purification of an intermediate are not needed, postprocessing is liable to operate, requirement on equipment is not high, the industrial production is facilitated.
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Paragraph 0027-0032; 0033-0038; 0039-0042; 0043-0046
(2017/08/27)
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- A he west for favorable department method of preparation
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The invention discloses a method for preparing cetilistat, which belongs to the technical field of the medicine preparation method, and is used for solving the problems of high three wastes, low yield and high cost in the current preparation method. The method comprises the following steps: 1)esterifying a compound A(2-amino-5-methyl benzoic acid) or its salt; 2) acylating an esterification object in the step 1) and chloroformic acid n-cetanol ester; 3)removing ester group of the compound obtained in the step 2) to obtain 2-(cetane carbonyl oxygen)amino-5-methyl benzoic acid; and 4)cyclizing the compound in the step 3) to obtain the target products. By improving the production steps, the invention provides the synthetic method with simple operation, high efficiency, and convenient industrial production for the cetilistat product.
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- A preparing method of a lipase inhibitor
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The invention belongs to the technical field of medicines, and particularly relates to a preparing method of 2-(hexadecyloxy)-6-methyl-4H-3,1-benzoxazin-4-one that is a lipase inhibitor. An intermediate that is hexadecyl-2-halogen-5-methyl-benzoyl carbamate shown as a formula (II) is subjected to amide cyclization and rearrangement with N-acyl-2-halogenobenzene under catalysis of a catalyst to prepare 1-(2-halogenbenzyl)-1,3-dione. -NH in imide and halogen are subjected to dehydrohalogenation to form a lactam four-membered ring firstly, and then the benzoxazin-4-one structure is formed by a C-N rearrangement reaction. The method is characterized by high product purity, simple, feasible and safe processes and capability of meeting requirements of industrial production.
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- Preparation method of cetilistat
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The invention discloses a preparation method of cetilistat; the method has the advantages of concise process, easily obtained raw materials, and mild reaction conditions, and is suitable for industrialized production. According to a reaction route, 2-amino-5-methyl benzoic acid and hexadecyl chloroformate serve as starting raw materials, firstly, amino acylation is carried out, an intermediate is purified, then cyclization is carried out, and the target compound is obtained through a two-step reaction.
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Paragraph 0063; 0064; 0065
(2016/10/09)
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- Method for preparing cetilistat
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The invention provides a method for preparing cetilistat. According to the method, 2-amidogen-5-methyl benzoic acid is adopted as an initial raw material, under existence of pyridine, the 2-amidogen-5-methyl benzoic acid reacts with chlorine acid cetyl alcohol ester in the first place, a midbody 2-(((hexadecane oxygroup) carbonyl) amidogen)-5-methyl benzoic acid is obtained, then dehydrogenation cyclization reagent is utilized to obtain the cetilistat, and the feeding sequence in step 1 is the 2-amidogen-5-methyl benzoic acid, alkali and the chlorine acid cetyl alcohol ester in sequence. The method has the remarkable advantages that the route is simple, operation is less, atom economy is better than that of other routes, and the cetilistat is suitable for large-scale production; the purity of the cetilistat at the reaction endpoint is larger than 98%, and through simple postprocessing, a final product which meets medical standards can be obtained, wherein the purity is larger than 99.5%, and the single impurity is smaller than 0.1%; the utilized solvent including dichloromethane and pyridine can be recycled for mechanical application, and the method is environmentally friendly.
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Paragraph 0058; 0059; 0060; 0061; 0062
(2016/12/12)
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- Process for preparing carbamic ester derivatives
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An improved process for preparing carbamic ester derivatives of the general formula (1) by reaction with carbon monoxide and water in the presence of a palladium catalyst is provided.
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- 2-OXY-BENZOXAZINONE DERIVATIVES FOR THE TREATMENT OF OBESITY
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The use of a compound comprising formula (I): (I) or a salt, ester, amide or prodrug therof in the inhibition of an enzyme whose preferred mode of action is to catalyse the hydrolysis of an ester functionality, e. g. in the control and inhibition of unwanted enzymes in products and processes. The compounds are also useful in medicine e.g. in the treatment of obesity and related conditions. The invention also relates to novel compounds within formula (I), to processes for preparing them and pharmaceutical compositions containing them. In formula (I) A is a 6-membered aromatic or heteroaromatic ring; and R1 is a branched or unbranched alkyl (optionally interrupted by one or more oxygen atoms), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, reduced aryl, reduced heteroaryl, reduced heteroarylalkyl or a substituted derivative of any of the foregoing groups.
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