33results about How to "Reflect the effect of green environmental protection" patented technology

The invention discloses a preparation method of Alectinib. The method comprises the steps that tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoate and 4-(piperidin-4-yl)-morpholine are subjected to a substitution reaction; obtained tert-butyl 4-{4-ethyl-3-[4-(morpholine-4-yl)piperidin-1-yl]phenyl}-4-methyl-3-oxopentanoate is subjected to a cyclization reaction and hydrolysis reaction, obtained 6-cyano-2-{2-[4-ethyl-3-(4- morpholine-4-yl)piperidin-1-yl)phenyl]prop-2-yl}-1H-indole-3-carboxylic acid is subjected to the cyclization reaction, and the Alectinib is obtained. According to the method, the operation is simplified, the cost is low, and the method is an environment-friendly technical method and suitable for industrial production.

The invention discloses a preparation method for alectinib. The preparation method comprises the following steps: with 2-{4-bromo-3[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-2-methylethyl propionate as a raw material, carrying out a reduction reaction to reduce the raw material into aldehyde; then subjecting the prepared aldehyde and tert-butyl 2,2-dichloroacetate to an addition-rearrangement reaction; then subjecting obtained 3-chloro-4-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-tert-butyl 2-oxovalerate to a substitution reaction; carrying out a cyclization reaction and a hydrolysis reaction on prepared 3-(3-cyanophenylamino)ethyl-4-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-tert-butyl 2-oxovalerate; subjecting obtained 6-cyano-2-{2-[4-bromo-3-(4-(morpholin-4-yl)piperidin-1-yl)phenyl]prop-2-yl}-1H-indole-3-carboxylic acid to a cyclization reaction; and successively carrying out a boric acid reaction and a catalytic coupling reaction on obtained 9-bromo-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-formonitrile so as to obtain alectinib. The method has the advantages of simple operation and low cost, and is a green environment-friendly process suitable for industrial production.

The invention discloses a preparation method for alectinib. The preparation method comprises the following steps: subjecting 2-4-{4-ethyl-3[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-2-methylethyl propionate to a reduction reaction; then subjecting prepared 2-{4-ethyl-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-2-methylpropionaldehyde and tert-butyl 2,2-dichloroacetate to an addition-rearrangement reaction; then subjecting obtained 3-chloro-4-{4-ethyl-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-tert-butyl 2-oxovalerate and m-aminobenzonitrile to a substitution reaction; then carrying out a cyclization reaction and a hydrolysis reaction on prepared 3-(3-cyanophenylamino)ethyl-4-{4-ethyl-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-tert-butyl 2-oxovalerate; and subjecting obtained 6-cyano-2-{2-[4-ethyl-3-(4-(morpholin-4-yl)piperidin-1-yl)phenyl]prop-2-yl}-1H-indole-3-carboxylic acid to a cyclization reaction so as to obtain alectinib. The method has the advantages of simple operation and low cost, and is a green environment-friendly process suitable for industrial production.

The invention discloses a preparation method of an alectinib intermediate, tert-butyl 4-{4-ethyl-3-[4-(morpholine-4-yl)piperidine-1-yl]phenyl}-4-methyl-3-oxovalerate. The preparation method comprises: subjecting ethyl 2-(4-ethyl-3-hydroxyphenyl)acetate and triflic anhydride to triflic acid esterification; subjecting the obtained 5-[(ethoxycarbonyl)methyl]-2-ethylphenyltriflate and 4-(4-piperidyl)morpholine to substitution reaction; subjecting the obtained ethyl 2-{4-ethyl-3-[4-(morpholine-4-yl)piperidine-1-yl]phenyl}acetate and methyl iodide to bis-methylation reaction; hydrolyzing the obtained ethyl 2-{4-ethyl-3-[4-(morpholine-4-yl)piperidine-1-yl]phenyl}-2-methylpropanoate; subjecting the obtained 2-{4-ethyl-3-[4-(morpholine-4-yl)piperidine-1-yl]phenyl}-2-methylpropanoic acid and mono-tert-butyl malonate to condensation reaction to obtain the alectinib intermediate. The preparation method is simple to perform and low in cost, is a green technique and is applicable to industrial production.

A kind of synthetic method of Erecoxib, step: with (E)-1-p-methylsulfonylphenyl-1-nitro-2-p-tolylethylene and isocyanoacetate in the mixture of alkali reagent and solvent The condensation cyclization reaction is carried out in the system; the obtained 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylate is reduced at -78°C in a system of reducing agent and solvent Reaction; The obtained 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-formaldehyde is oxidized in the system of hydrogen peroxide and solvent; the obtained 3-p-methylphenyl-4- Perform substitution reaction between p-methylsulfonylphenyl-3-pyrrolidin-2-one and 1-halopropane or hydrocarbon sulfonate propyl ester derivatives in a system of alkali reagent and solvent to obtain Erecoxib. The reaction steps are simplified and optimized, and the process operation is simple, which helps to reduce the cost; the impurities in the reaction are less and controllable, reflecting green environmental protection; the starting materials and the reagents used are easily available.

The invention discloses a filgotinib synthetic method and belongs to the technical field of chemical synthesis of medicines. 6-chloro-2-aminopyridine and di-tert-butyl dicarbonate ester are subjected to condensation reaction to obtain 6-chloro-2-tert-butyloxycarbonyl aminopyridine; hydrolysis reaction is performed; the obtained 6-chloro-2-tert-butyloxycarbonyl aminopyridine and trifluorinated methyl sulfonic anhydride are subjected to trifluoromethanesulfonic acid esterification reaction; the obtained 2-tert-butyloxycarbonylamino-6-pyridyltrifluoromethanesulfonate and [(1,1-dioxo-4-thiomorpholinyl)methyl]benzo-4-boronic acid pinacol ester are subjected to condensation reaction to obtain a tert-butyl ester derivative; the tert-butyl ester derivative is treated by trifluoroacetic acid and subjected to de-protection; the obtained intermediate and ethoxycarbonyl isothiocyanate are subjected to isothiocyanate reaction; the obtained intermediate and hydroxylamine hydrochloride are subjected to ring closing reaction; the obtained intermediate and cyclopropane carbonyl chloride are subjected to amidation reaction to obtain the finished product. Operation is simplified; reagents are available; the concept of environment friendliness and environment protection is embodied.

The invention discloses a method for synthesizing a monosaccharide intermediate of fondaparinux sodium, which uses 1,2-O-isopropylidene-3-O-benzyl-α-D-glucofuranose as a raw material, through mixing with benzene Esterification reaction of formic acid, esterification reaction with substituent sulfonic anhydride and / or substituent sulfonyl chloride, followed by hydrolysis reaction and addition of sulfuric acid aqueous solution to obtain fondaparinux sodium monosaccharide fragment intermediate 1,6-dehydration ‑3‑O‑Benzyl‑β‑L‑Idopyranose. The synthesis method has simple process, less side reaction impurities and high yield, and is suitable for process scale-up synthesis to meet the industrial production of fondaparinux sodium.

An Apatinib intermediate and its preparation method belong to the technical field of pharmaceutical chemical synthesis. The chemical name of the Apatinib intermediate is 1-{4-[(2-((4-pyridyl methyl)amino)pyridine-3-yl)carbonylamino]phenyl}cyclopentanecarboxylic alkyl ester. The preparation method comprises the following steps: 4-aminophenylacetic alkyl ester and 2-Chloronicotinyl chloride are subjected to an amidation reaction in a system of an acid-binding agent base and a solvent to obtain 4-[(2-chloropyridine-3-yl)carbonylamino]phenylacetic alkyl ester; the product and 4-aminomethylpyridineare subjected to a substitution reaction in a system of an acid-binding agent base and a solvent to obtain 4-{[2-((4-pyridylmethyl)amino)pyridine-3-yl]carbonylamino}phenylacetic alkyl ester; and theproduct and 1,4-dihalogenbutane are subjected to a condensation reaction to obtain a finished product. The technology is simple, is low-cost, is green and environmentally-friendly, and is suitable forindustrial production.

The invention belongs to the field of medicine synthesis and provides a novel idelalisib preparation method. The novel idelalisib preparation method includes steps: in an appropriate solvent, subjecting a compound A to nucleophilic substitution reaction with B in existence of an acid-binding agent to obtain an intermediate C; hydrolyzing the compound C into an intermediate D under appropriate alkali action; subjecting the intermediate D and a compound E to condensation to obtain an intermediate F; in an appropriate solvent, subjecting the intermediate F to ring closing reaction under a catalytic system of HMDS (hexamethyl disilazane) / lewis acid to obtain a final product namely idelalisib.

The invention discloses a synthesis method of Alectinib. The method comprises the following steps: carrying out a borating reaction between 6-bromo-3,4-dihydro-2-naphthalenone and n-butyl lithium and then an organic boron reagent; carrying out a catalytic coupling reaction between the obtained 3,4,-dihydro-2-naphthalenone-6-boric acid and bromoethane; carrying out a dimethylation reaction between the obtained 6-ethyl-3,4-dihydro-2-naphthalenone and iodomethane; carrying out a bromination reaction between the obtained 1,1-dimethyl-6-ethyl-3,4-dihydro-2-naphthalenone and a bromination reagent; carrying out a substitution reaction between the obtained 1,1-dimethyl-6-ethyl-7-bromo-3,4-dihydro-2-naphthalenone and 4-(4-piperidyl)morpholine; carrying out a cyclization reaction between the obtained 1,1-dimethyl-6-ethyl-7-[4-(morpholine-4-yl)piperidine-1-yl]-3,4-dihydro-2-naphthalenone and 3-cyanophenylhydrazine; and carrying out an oxidation reaction between the obtained 9-ethyl-6,6-dimethyl-8-[4-(morpholine-4-yl)piperidine-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-formonitrile and dichlorodicyanobenzoquinone to obtain a finished product of Alectinib. The synthesis method has the advantages of relatively short route, simplified operation and relatively low cost and is a green and environment-friendly method suitable for industrial production.

The invention discloses a method for synthesizing Erecoxib, which belongs to the technical field of pharmaceutical chemical synthesis. Step: Synthesis of 2-n-propylamino-1-p-methylsulfonyl acetophenone: N-propyl-β-hydroxyl-4-methylsulfonyl phenethylamine in a system composed of oxidation reagent, solvent and water Carry out oxidation reaction in, obtain 2-n-propylamino-1-p-methylsulfonyl acetophenone; Synthetic Erecoxib: the 2-n-propylamino-1-p-methylsulfonyl acetophenone obtained and p- Cresyl acetate undergoes condensation cyclization reaction in a system of alkali reagent and solvent to obtain Erecoxib. The reaction steps are significantly simplified and optimized, and the process operation is simple, which helps to reduce the cost; the reaction has less impurities and is controllable, and no pollutants are produced, reflecting the effect of environmental protection; the starting materials and reagents used are easily available and can be produced in large quantities To meet the use requirements of raw materials and suitable for industrial production.

The invention discloses a method for preparing a monosaccharide intermediate of fondaparinux sodium. Using glucosamine protected at positions C4 and C6 as raw materials, methyl 3‑O is obtained through methylation, amidation and benzylation. ‑Benzyl‑4,6‑O‑benzylidene‑2‑(benzyloxycarbonyl)amino‑2‑deoxy‑α‑D‑glucopyranoside, and then undergo a dehydroxyl protecting group protection reaction to obtain fondaparin Sodium decyl monosaccharide fragment intermediate methyl 3‑O‑benzyl‑2‑(benzyloxycarbonyl) amino‑2‑deoxy‑α‑D‑glucopyranoside. The preparation method has simple process, less impurities in side reactions, and high yield, and is suitable for process scale-up preparation to meet the industrial production of fondaparinux sodium.

The invention relates to a preparation method for apatinib. The preparation method comprises the following steps: performing condensation reaction on 4-(tert-butoxycarbonyl group) alkyl phenylacetateand 1,4-butane dihalide, thereby acquiring 1-[4-(tert-butoxycarbonyl group) phenyl] alkyl cyclopentane formate; performing deprotection reaction on the acquired product, thereby acquiring 1-(4-aminophenyl) alkyl cyclopentane formate; performing amidation reaction on the acquired product and 2-chloronicotinoyl chloride, thereby acquiring 1-{4-[(2-chlorine pyridine-3-group) carbonyl amino] phenyl} alkyl cyclopentane formate; performing substitution reaction on the acquired product and 4-aminomethyl pyridine, thereby acquiring 1-{4-[(2-((4-pyridyl methyl) amino) pyridine-3-group) carbonyl amino]phenyl} alkyl cyclopentane formate; performing amidation reaction on the acquired product, thereby acquiring 1-{4-[(2-((4-pyridyl methyl) amino) pyridine-3-group) carbonyl amino] phenyl} cyclopentaneformamide; lastly, dehydrating, thereby acquiring an end product.