30 results about "Boceprevir" patented technology

The invention relates to a synthetic method of a boceprevir intermediate, namely (1R, 2S, 5S)-6, 6-dimethyl-3-aza-bicyclo-[3. 1. 0] hexane-2-carboxylic acid methyl ester hydrochloride, belonging to the technical field of drug synthesis. The synthetic method solves the problems of high cost, complex reaction, low yield, and the like of the synthesis of the boceprevir intermediate in the prior art. The synthetic method comprises the following steps of carrying out amino protection on 6, 6-dimethyl-3-aza-bicyclo-[3. 1. 0] hexane hydrochloride which is taken as an original raw material; then reacting 6, 6-dimethyl-3-aza-bicyclo-[3. 1. 0] hexane hydrochloride with 1, 2, 3, 4-tetralin-1-naphthylamine for 3-4 hours at 30-35 DEG C under the action of a hydrogen drawing reagent by taking 4, 4'-difluoro benzophenone as a chiral inductive agent; finally removing an amino protecting group, and adding acid to form salt to directly obtain a final product. The synthetic method disclosed by the invention has the advantages of low cost, simple reaction condition, few reaction steps, short time and high purity and yield of the final product, namely the boceprevir intermediate.

The invention relates to the technical field of a preparing method of an anti-hepatitis C medicine Boceprevir. A compound 1 provided by the invention has a structural formula shown as the attached drawing. The operation of the compound preparation is simple and convenient, and the yield is higher. The compound can be used for synthesizing the anti-hepatitis C medicine Boceprevir, and a new thought and method can be provided for synthesis of the anti-hepatitis C medicine Boceprevir. In addition, ultraviolet chromophoric groups are contained in molecules of the compound, the detection is more convenient than that of an ordinary synthesis method, and side reaction caused by oxhydryl nucleophilicity in a condensation step is avoided through the introduction of benzyls onto oxhydryls. Compared with the synthesis method in the prior art, the preparing method provided by the invention has certain advantages.

The present invention provides methods, pharmaceutical compositions, medicaments, and pharmaceutical kits that employ the use of boceprevir as a CYP3A4 / 5 inhibitor to improve the pharmacokinetics of therapeutic compounds metabolized by cytochrome P450 3A4 / 5 (CYP3A4 / 5) enzymes.

The invention relates to a one-pot synthetic method for the intermediate of boceprevir, i.e., N-t-butyl-aminocarbonyl-3-methyl-L-valine, which belongs to the technical field of drug synthesis. The synthetic method comprises the following steps: dissolving tert-butylamine in a solvent to form a reaction solution, cooling the reaction solution to a temperature of -5 to 5 DEG C, adding N,N'-carbonyldiimidazole into the reaction solution and carrying out a reaction with stirring for 20 to 40 min until a compound represented by formula (I) is obtained after completion of the reaction; and then adding L-leucine into the reaction solution, carrying out a reaction with stirring for 20 to 40 min until the reaction is finished, adding the totally reacted reaction solution into ice water and carrying out extraction, pressure reduced concentration, pulping, pumping filtration and vacuum drying so as to obtain N-t-butyl-aminocarbonyl-3-methyl-L-valine. The synthetic method has the advantages of cheap and easily available raw materials, greenness, environment friendliness, simple reaction conditions, a high conversion rate, a few generated by-products and high yield and purity of the product, N-t-butyl-aminocarbonyl-3-methyl-L-valine.

The invention relates to the technical field of preparation methods for anti-hepatitis C drug Boceprevir. The structural formula of compound VI (D) provided by the present invention is as follows. The preparation of this type of compound has the advantages of simple operation and high yield. The compound can be used for the synthesis of the anti-hepatitis C drug Boceprevir, which provides a new idea and method for the synthesis of the anti-hepatitis C drug Boceprevir. Moreover, the ultraviolet chromogenic group in the molecule of this type of compound is more convenient to detect than the original synthesis method. In addition, the introduction of the benzyl group on the hydroxyl group avoids the side reaction caused by the nucleophilicity of the hydroxyl group in the condensation step, which is different from the existing synthetic method. Compared with certain advantages.

The invention relates to the technical field of preparation methods for anti-hepatitis C drug Boceprevir. The structural formula of compound V (E) provided by the present invention is as follows. The preparation of this type of compound has the advantages of simple operation and high yield. The compound can be used for the synthesis of the anti-hepatitis C drug Boceprevir, which provides a new idea and method for the synthesis of the anti-hepatitis C drug Boceprevir. Moreover, the ultraviolet chromogenic group in the molecule of this type of compound is more convenient to detect than the original synthesis method. In addition, the introduction of the benzyl group on the hydroxyl group avoids the side reaction caused by the nucleophilicity of the hydroxyl group in the condensation step, which is different from the existing synthetic method. Compared with certain advantages.

The present invention relates to the technical field of a method for preparation of an anti-HCV drug Boceprevir. The present invention provides compounds IV (F-1) of a formula as follows. The preparation of the compounds is simple and of high yield. The compounds can be used for synthesis of the anti-HCV drug Boceprevir. The present invention provides new implication and an approach for the synthesis of the anti-HCV drug Boceprevir. Furthermore, a UV chromophore of the compounds makes the compounds more convenient to detect than compounds prepared by a conventional synthesis method, and additionally introduction of a benzyl group to a hydroxyl group avoids side reactions caused by the nucleophilicity of the hydroxyl group during a condensation step. There are certain advantages compared to an existing synthesis method.

The invention relates to a synthesis method of beta-amino-alpha-hydroxycyclohexyl butyl aluminum hydrochloride as a boceprevir intermediate. The synthesis method comprises the following steps of: with Boc-tert-butyl glycinate as a compound as shown in the formula (I) as a starting raw material, subjecting the Boc-tert-butyl glycinate and cyclobutyl halogenated methane as a compound as shown in the formula (II) to reaction to generate a compound as shown in the formula (III), reducing the compound to generate a compound as shown in the formula (IV), adding a cyanide and inorganic acid to generate a compound as shown in the formula (V), subjecting the compound and acid to reaction to generate a compound as shown in the formula (VI), adding a hydroxyl protective agent and a catalyst to react to generate a compound as shown in the formula (VII), oxidizing the compound to generate a compound as shown in the formula (VIII), and finally, adding acid to react to generate the beta-amino-alpha-hydroxycyclohexyl butyl aluminum hydrochloride (IX). The synthesis method is few in synthesis step, short in time, less in required auxiliary reagent, low in cost, simple and feasible in after-treatment, simple in equipment and higher in purity and yield.

The invention relates to the technical field of a preparing method of an anti-hepatitis C medicine Boceprevir. A compound 1 provided by the invention has a structural formula shown as the attached drawing. The operation of the compound preparation is simple and convenient, and the yield is higher. The compound can be used for synthesizing the anti-hepatitis C medicine Boceprevir, and a new thought and method can be provided for synthesis of the anti-hepatitis C medicine Boceprevir. In addition, ultraviolet chromophoric groups are contained in molecules of the compound, the detection is more convenient than that of an ordinary synthesis method, and side reaction caused by oxhydryl nucleophilicity in a condensation step is avoided through the introduction of benzyls onto oxhydryls. Compared with the synthesis method in the prior art, the preparing method provided by the invention has certain advantages.

The present invention belongs to the technical field of preparation methods of anti-hepatitis C virus drugs. The structural formula of a compound F-2 disclosed in the invention is as follows. The compound is easy to prepare, the preparation method is easy to operate, and the yield of the compound is high. The compound can be used for synthesis of an anti-hepatitis C virus drug Boceprevir, and a new concept and a new method for synthesis of the anti-hepatitis C virus drug Boceprevir can be provided. Compared with the existing synthesis method, the compound prepared by the preparation method can be more conveniently detected due to ultraviolet chromophoric groups in the molecule of the compound, introduction of a benzyl group to a hydroxyl group avoids side reactions in a condensation step which are caused by hydroxyl nucleophilicity, and thus the preparation method has certain advantages over the existing synthesis method.

The invention relates to a one-pot synthetic method for the intermediate of boceprevir, i.e., N-t-butyl-aminocarbonyl-3-methyl-L-valine, which belongs to the technical field of drug synthesis. The synthetic method comprises the following steps: dissolving tert-butylamine in a solvent to form a reaction solution, cooling the reaction solution to a temperature of -5 to 5 DEG C, adding N,N'-carbonyldiimidazole into the reaction solution and carrying out a reaction with stirring for 20 to 40 min until a compound represented by formula (I) is obtained after completion of the reaction; and then adding L-leucine into the reaction solution, carrying out a reaction with stirring for 20 to 40 min until the reaction is finished, adding the totally reacted reaction solution into ice water and carrying out extraction, pressure reduced concentration, pulping, pumping filtration and vacuum drying so as to obtain N-t-butyl-aminocarbonyl-3-methyl-L-valine. The synthetic method has the advantages of cheap and easily available raw materials, greenness, environment friendliness, simple reaction conditions, a high conversion rate, a few generated by-products and high yield and purity of the product, N-t-butyl-aminocarbonyl-3-methyl-L-valine.

This invention relates to novel compounds that are peptides derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel peptides that are deuterated derivatives of boceprevir. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating HCV infection.

The invention relates to the technical field of a preparing method of an anti-hepatitis C medicine Boceprevir. A compound VIII (B) provided by the invention has a structural formula shown as the attached drawing. The operation of the compound preparation is simple and convenient, and the yield is higher. The compound can be used for synthesizing the anti-hepatitis C medicine Boceprevir, and a new thought and method can be provided for synthesis of the anti-hepatitis C medicine Boceprevir. In addition, as ultraviolet chromophoric groups are contained in molecules of the compound, the detection is more convenient than that of an ordinary synthesis method, and side reaction caused by oxhydryl nucleophilicity in a condensation step is avoided through the introduction of benzyls on oxhydryls. Compared with the synthesis method in the prior art, the preparing method provided by the invention has certain advantages.

The invention relates to a synthetic method of a boceprevir intermediate namely 2-hydroxy-3-amino-4-cyclobutane amide hydrochloride, belonging to the technical field of medicament synthesis. By adopting the synthetic method, the problems that a method for synthesizing the boceprevir intermediate is high in cost, complex in reaction, low in efficiency and the like in the prior art can be solved. The synthetic method comprises the following steps: by adopting cyclobutyl acetate and monomethyl mono potassium malonate as raw materials, reacting for 10-12 hours at room temperature under the action of an activating agent and magnesium chloride; sequentially adding an oxidizing agent, 4-cyclobutyl-3-oxo-ethyl butyrate and a catalyst into methanoic acid at 15-20 DEG C, and reacting for 1.5-2.5 hours at 15-20 DEG C; adding a condensation agent and organic alkali at 10-15 DEG C, performing condensation reaction with ammonium chloride at room temperature, and reacting for 10-12 hours; and finally performing ammoniation and acidification to obtain a final product. The synthetic method disclosed by the invention is relatively low in cost, simple in reaction condition, less in reaction step and short in time, and the final product, namely the boceprevir intermediate, is relatively high in purity and yield.

The present invention relates to the technical field of a method for preparation of an anti-HCV drug Boceprevir. The present invention provides compounds VII (C) of a formula as follows. The preparation of the compounds is simple and of high yield. The compounds can be used for synthesis of the anti-HCV drug Boceprevir. The present invention provides new implication and approach for the synthesis of the anti-HCV drug Boceprevir. Furthermore, a UV chromophore of the compounds makes the compounds more convenient to detect than compounds prepared by aconventional synthetic method, and introduction of a benzyl group to a hydroxyl group avoids side reactions during a condensation step due to the nucleophilicity of the hydroxyl group. There are certain advantages compared to an existing synthetic method.

The present invention relates to the technical field of a method for preparation of an anti-HCV drug Boceprevir. The present invention provides compounds F of a formula as follows. The preparation of the compounds is simple and of high yield. The compounds can be used for synthesis of the anti-HCV drug Boceprevir. The present invention provides new implication and approach for the synthesis of the anti-HCV drug Boceprevir. Furthermore, a UV chromophore of the compounds makes the compounds more convenient to detect than compounds prepared by a conventional synthetic method, and introduction of a benzyl group to a hydroxyl group avoids side reactions during a condensation step due to the nucleophilicity of the hydroxyl group. There are certain advantages compared to an existing synthesis synthetic method.

The present invention discloses a compound and applications of the compound in preparation of anti-hepatitis C virus drugs, wherein the structure formula of the compound is represented by a formula I or II, and the compound represented by the formula I or compound represented by the formula II can be subjected to drug combination with other anti-virus drugs such as interferon (PEG IFN-[alpha]), ribavirin (RBV), boceprevir, telaprevir, simeprevir, sofosbuvir, daclatasvir and the like t prepare anti-HCV products and other anti-virus infection products. According to the present invention, the compound has rich functional group diversity and modificability, and the product is relatively easy to separate and purify; the compounds can well inhibit HCV and other viruses, are obtained through phenotype screening, have different antiviral mechanisms, have extremely novel and innovated structures in the anti-virus field, and are not reported in the prior art; and the compound of the present invention has broad development and application prospect.

The present invention relates to the technical field of a method for preparation of an anti-HCV drug Boceprevir. The present invention provides compounds IV (F-1) of a formula as follows. The preparation of the compounds is simple and of high yield. The compounds can be used for synthesis of the anti-HCV drug Boceprevir. The present invention provides new implication and an approach for the synthesis of the anti-HCV drug Boceprevir. Furthermore, a UV chromophore of the compounds makes the compounds more convenient to detect than compounds prepared by a conventional synthesis method, and additionally introduction of a benzyl group to a hydroxyl group avoids side reactions caused by the nucleophilicity of the hydroxyl group during a condensation step. There are certain advantages compared to an existing synthesis method.