- Preparation method of loxoprofen
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The invention discloses a novel preparation method of loxoprofen (I). The reaction process comprises the following steps: a compound (VII) and a compound (VIII) are subjected to a condensation reaction to obtain an intermediate (IX), the intermediate (IX) is subjected to a hydrogenation reduction reaction in a mixed solvent of acid and alcohol to obtain an intermediate (X), and the intermediate (X) is subjected to a hydrolysis reaction to obtain loxoprofen (I).
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Paragraph 0038; 0046-0048
(2020/07/27)
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- Preparation method of aryl propionic acid compound
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The invention provides a preparation method of an aryl propionic acid compound, wherein the preparation method comprises the following steps: carrying out acetylation reaction on substituted aryl benzene to obtain aryl acetophenone; carrying out hydrogenation reduction reaction on alpha-substituted aryl ethyl ketone to obtain alpha-substituted aryl ethanol; and in an acidic solution, introducing carbon monoxide gas into the alpha-substituted aryl ethanol, and carrying out a carbonylation reaction under the co-catalytic action of a main catalyst and a cocatalyst to obtain the aryl propionic acid compound, wherein the cocatalyst has the following structural formula described in the specification, R1 is one of hydrogen and a substituted carboxylic acid group, and R2 is one of hydrogen, halogen, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C12 naphthenic base, substituted carbonyl containing C6-C24 aryl or substitutedaryl, substituted carbonyl containing C3-C12 heterocyclic radical or substituted heterocyclic radical, phenyl, substituted phenyl, naphthyl and substituted naphthyl.
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Page/Page column 0121-0125
(2020/10/04)
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- Synthetic method of loxoprofen
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The invention discloses a synthetic method of an intermediate loxoprofen for preparing a phenylpropionic acid non-steroidal anti-inflammatory drug loxoprofen sodium. The synthetic method comprises thefollowing steps: firstly, carrying out acylation reaction on a compound VII and a compound VIII in a solvent 1 under the action of lewis acid serving as a catalyst to obtain an intermediate compoundIX; and introducing hydrogen into the intermediate compound IX in a solvent 2 under the action of strong acid by taking palladium on carbon as a catalyst, and carrying out hydrogenation tert-butyl ester removal reaction to obtain loxoprofen. The synthetic method has the advantages that the synthetic route is short, simple in process and convenient to operate, no corrosive strong acid is used in the synthesis process, and the reaction control temperature in the synthesis process is relatively mild; and the synthetic method has the characteristics of no product carbonization, no corrosion to equipment, safe and environment-friendly synthesis process, suitability for industrial production and the like, and the finally obtained product loxoprofen has high yield which can reach 65.8-73.3% and purity of 99.54-99.69% from the beginning of the compound VIII.
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Paragraph 0034; 0083; 0089-0090; 0095; 0100-0101
(2020/08/02)
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- A substituted phenylacetic acid derivatives (by machine translation)
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The invention belongs to the field of drug synthesis, relates to a substituted phenylacetic acid derivatives, in particular to the preparation of 2 - [4 - (2 - methyl oxygen fifth heavenly stem) hydrocinnamic acid] preparation method. If nitrile alkylation reaction include alkylation reaction, reaction or ester alkyl [...] reaction to prepare the intermediate type II - 2 or type II - 2' compound, After the hydrolytic reaction or oxidation reaction preparation to obtain the product. The invention relates to the alkylation reaction without additional solvent, is a more industrialization of the advantages of the line. (by machine translation)
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Paragraph 0053; 0054
(2019/04/18)
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- Preparation method for substituted phenylacetic acid derivative
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The invention belongs to the field of medicament synthesis, relates to a preparation method for a substituted phenylacetic acid derivative, in particular to a preparation method for preparing 2-[4-(2-oxygen amyl methyl)phenylpropionic acid]. A dihalobenzyl compound or a disubstituted benzyl compound reacts with a compound of cyclopentanone or a precursor form compound thereof to prepare a precursor compound of Loxoprofen which is as shown in the description, wherein X is a halogen, L1 is a halogen, OH, OMs, OTs and OTf, L2 is a halogen, a cyanogroup, a hydroxide radical, -CH2OH, -CHO, nitromethane, an ester group, -NR4R5, OTf, OTs, OMs, -C=CR6 and -C is equivalent to CR7, wherein R4, R5, R6 and R7 are low substituted alkyl group; Z is cyclopentanone or the precursor form thereof; the precursor form is as shown in the description; and R3 is a low substituted alkyl group. Further, the preparation method comprises a step of converting the cyclopentanone precursor form into cyclopentanone;and the precursor compound of the Loxoprofen is used for preparing a Loxoprofen compound.
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Paragraph 0088; 0089
(2019/03/29)
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- New method for synthesizing loxoprofen sodium
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The invention belongs to the field of synthesis of organic matters and specifically relates to a new method for synthesizing loxoprofen sodium. The synthesis method is characterized by taking 2-(4-bromomethyl) phenylpropionic acid as a raw material and performing a 4-step reaction to prepare the loxoprofen sodium. The new method for synthesizing the loxoprofen sodium adopted by the invention has the effects that the yield is increased and the industrial prospect is good.
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- Synthesis method of loxoprofen sodium
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The invention discloses a synthesis method of loxoprofen sodium, which comprises the following steps of: step 1), preparing N-(1-cyclopentenyl) morpholine; step 2), preparing 2-(4-bromomethyl phenyl)methyl propionate, the method also comprises the following step 3), preparing loxoprofen sodium by an enamine alkylation method: first dissolving 2-(4-bromomethyl phenyl) methyl propionate in a solvent, adding N-(1-cyclopentenyl) morpholine and the solvent in a container, dropwise adding 2-(4-bromomethyl phenyl) methyl propionate solution under reflux conditions; continuing reacting under reflux conditions after the completion of the dropwise addition; adding alkali solution after obtained reaction liquid is cooled, hydrolysising and separating to obtain an organic phase and an aqueous phase respectively, extracting the aqueous phase with an extractant to obtain extract liquid and the aqueous phase after extraction respectively, and post-treating the aqueous phase after extraction to obtain loxoprofen sodium. The preparation of loxoprofen sodium by the above method has the advantages of simple reaction steps, high yield of loxoprofen sodium and low production cost.
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- Method for synthesizing high-purity non-steroidal anti-inflammatory drug loxoprofen sodium
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The invention discloses a method for synthesizing high-purity non-steroidal anti-inflammatory drug loxoprofen sodium, 2-(4-bromomethylphenyl) methyl propionate b is synthesized by esterification of raw material a and methanol, intermediate compound c and loxoprofen acid are synthesize sequentially, and the loxoprofen sodium is finally synthesized. The reaction mechanism is simple, by-products arefew, synthesis steps are easy to control, the raw material is easily available, and the impurity content of each step is strictly controlled. The purifying method is easy to operate and suitable for industrial production. The white flake crystal loxoprofen sodium is prepared. Finally, HPLC analysis shows that the loxoprofen sodium content detected by HPLC is as high as 99.95%.
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Paragraph 0064; 0065; 0066; 0067; 0068
(2018/09/13)
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- Loxoprofen sodium and preparation method of intermediate of loxoprofen sodium
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The invention relates to the technical field of organic synthesis and in particular relates to loxoprofen sodium and a preparation method of an intermediate of the loxoprofen sodium. The invention provides a compound with a structure shown as a formula A: the formula A is shown in the description, wherein R and R are independently selected from methyl or ethyl or can be subjected to cyclic synthesis to form a formula shown in the description respectively, wherein n is 1 or 2; Y is X or a formula shown in the description, wherein X is Cl or Br and R is methyl or ethyl.
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- GLYCOSAMINOGLYCAN DERIVATIVE AND METHOD FOR PRODUCING SAME
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The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.
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Paragraph 0416-0420
(2016/06/28)
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- Process for producing 2-substituted propionic acid
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Adipic acid diester is caused to react with alkoxide M(OR)n, wherein R is an alkyl group and M is an alkali metal or alkaline earth metal, the reaction product is successively subjected either to coupling with halomethylstyrene followed by carbonylation, or to coupling with 2-(halomethylphenyl)propionic acid or its ester followed by decarboxylation and hydrolysis. With this process, it is possible to produce more efficiently a specific 2-substituted propionic acid, loxoprofen.
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- Tetrabutylammonium peroxydisulfate in organic synthesis; VII. A facile and efficient method for the regeneration of carbonyl compounds from semicarbazones by tetrabutylammonium peroxydisulfate
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Semicarbazones of aldehydes and ketones are oxidized to the corresponding carbonyl compounds in excellent yields by tetrabutylammonium peroxydisulfate in dichlorlethane under mild conditions.
- Chen, Fen-Er,Liu, Ji-Dong,Fu, Han,Peng, Zuo-Zhong,Shao, Lan-Ying
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p. 2295 - 2299
(2007/10/03)
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- High molecular weight prodrug derivatives of antiinflammatory drugs
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Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.
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- Ophthalmic anti-inflammatory agents
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Compounds of formula: STR1 (wherein R represents hydrogen or methyl, >A--B-- represents a >CH--CH2 -- or >C=CH-- group; >C--Z represents a >C=O or >CH--OH group; and n represents 1 or 2) and ophthalmically acceptable salts and esters thereof are useful as ophthalmic anti-inflammatory agents.
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- Synthesis and Antiinflammatory Activity of acetic Acids and Related Compounds
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acetic acid derivatives and related compounds were synthesized to test their antiinflammatory and analgesic activities.Some of the compounds in this series were found to have good activity in the carrageenan edema test.Among them, sodium 2-phenyl>propionate dihydrate (15) and 2-phenyl>propionic acid (13b) showed potent analgesic and antiadjuvant arthritis activities with excellent antipyretic properties.
- Terada, Atsusuke,Naruto, Shunji,Wachi, Kazuyuki,Tanaka, Shigeru,Iizuka, Yoshio,Misaka, Eiichi
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p. 212 - 216
(2007/10/02)
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- A NEW SYNTHESIS OF SOME NON-STEROIDAL ANTI-INFLAMMATORY AGENTS VIA CYANOPHOSPHATES
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A simple and convenient procedure for the syntheses of some non-steroidal anti-inflammatory agents, ibuprofen, rac-naproxen, clidanac and loxoprofen, is described.
- Hurusawa, Shinya,Nakamura, Shuji,Yagi, Sayoko,Kurihara, Takushi,Hamada, Yasumasa,Shioiri, Takayuki
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p. 1365 - 1372
(2007/10/02)
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- Optical Resolution and Determination of Absolute Configuration of (=/-)-2-propionic Acids
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The title compound, which was newly synthesized, showed good anti-inflammatory and analgesic activities.Optical resolution was performed by the following procedures: 1) condensation of the acid with (-)-1-phenylethylamine followed by separation of diasteromeric amides; 2) reduction of the cyclopentanone moiety and then acylation with optically active acid; 3) separation of epimeric esters followed by saponification of esters; 4) oxidation of alcohols to ketones; 5) saponification of amides.The absolute configurations of the four optically active compounds thus obtained were confirmed by circular dichroism spectroscopy.Keywords -- antiflammatory agent; 2-arylpropionic acid derivative; optical resolution; absolute configuration; CD; ORD
- Naruto, Shunji,Terada, Atsusuke
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p. 4286 - 4294
(2007/10/02)
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- Substituted phenylacetic acid derivatives and process for the preparation thereof
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4-(2-Oxo- or hydroxyimino-cycloalkan-1-ylmethyl)phenylacetic acid derivative and nontoxic pharmaceutically acceptable salt thereof are useful as an anti-inflammatory agent. The above 2-oxo-compound may be prepared by (a) hydrolyzing and decarboxylating 4-(1-alkoxycarbonyl-2-oxocycloalkan-1-ylmethyl)phenylacetic acid ester derivative or (b) reacting p-halomethylphenylacetic acid ester derivative with an enamine of cycloalkanone and hydrolyzing the resulting product. And further, the above 2-hydroxyimino-compound may be prepared by (c) reacting 4-(2-oxocycloalkan-1-ylmethyl)phenylacetic acid derivative (the product of process (a) or (b)) with hydroxylamine or (d) reacting a dilithium salt of cycloalkanone oxime with p-halomethyl- or p-sulfonyloxymethyl-phenylacetic acid ester derivative and hydrolyzing the resulting product.
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