32results about How to "The reaction is easy to scale up" patented technology

The present invention relates to a 6-tert-butyloxycarbonyl octahydro-2H-pyran[3,2-c]pyridine-8-carboxylic acid synthesis method. In the prior art, the suitable industrial synthesis method does not exist. A purpose of the present invention is to mainly solve the technical problem in the prior art. The synthesis method comprises six steps and specifically comprises that a compound 1 and 1-bromo-3-chloro-propane are subjected to an alkylation reaction to obtain a compound 2, an intramolecular cyclization reaction is performed to generate a compound 3, the double bond of the compound 3 is subjected to hydrogenation reduction to obtain a compound 4, and the compound 4 is subjected to hydrolysis to obtain a compound. The reaction formula is defined in the specification.

The present invention relates to a kind of 4,5-dihydro-1H,3H-pyrrolo[1,2-A][1,4]diazepine-2,4-dicarboxylic acid-2-tert-butyl ester The preparation method mainly solves the technical problem that there is no suitable industrial synthesis method at present. The present invention is divided into five steps. First, compound 1 is dissolved in acetonitrile and reacts with compound 2 at room temperature under the action of potassium carbonate to generate compound 3. The second step is the reductive amination of compound 2 and benzylamine in ethanol by adding sodium borohydride and simultaneous ring closure to obtain compound 4. Then in compound 4 ethanol solution, add 10% palladium carbon hydrogen to remove the benzyl protecting group of compound 4 to obtain compound 5, then in compound 5 methanol solution, pass through and BOC 2 O is reacted to obtain compound 6, and finally compound 6 is hydrolyzed by adding sodium hydroxide in a mixed solvent of methanol and water to obtain final product 7. The compound obtained in the present invention is a useful intermediate or product for the synthesis of many medicines.

The invention provides a preparation method of 3,3'-bisindole compounds. The preparation method comprises the following steps: adding 3-indolone derivatives, indole derivatives and a catalyst into a solvent, reacting and purifying. The reaction general formula of the preparation method is disclosed in the specification. The preparation method provided by the invention has the advantages of accessible raw materials, mild reaction conditions, simple synthesis steps, easy operation, easy separation and purification of the synthetic product, high yield of the target product, and easy amplification for reaction, and thus, has wide application prospects.

The invention relates to a synthesis method of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid, aiming at mainly solving the technical problem that a suitable industrial synthesis method does not exist at present. The synthesis method is divided into four steps as follows: firstly, taking a compound 1 to react with n-butyl lithium and benzyl chloroformate in tetrahydrofuran to obtain a compound 2; then, taking the compound 2 to react with diphenyl chlorophosphate and lithium hexamethyldisilazide to obtain a compound 3; inserting carbonyl into the compound 3 in the presence of CO under the action of palladium acetate and triphenylphosphine to obtain a compound 4; under the action of hydrogen and palladium on carbon, carrying out hydrogenation reduction again to obtain a target compound 5. A formula is shown I in the description. The compound prepared by the synthesis method is a useful immediate or product synthesized by a plurality of medicines.

The invention relates to a preparation method of 2-((1S3aR7aR)-5-tert-butyloxycarbonyltetrahydrofuro[3,4]piperidine-1)acetic acid. The preparation method comprises 11 steps: carrying out esterification on a dicarboxylic acid piperidine compound 1 in thionyl chloride to obtain a diester compound 2; then reducing a pyridine ring by utilizing palladium carbon to obtain a compound 3; then taking the compound 3 to react with Boc acid anhydride to obtain a Boc protected compound 4; hydrolyzing the compound 4 by utilizing lithium hydroxide to obtain a dicarboxylic acid compound 5; carrying out ring closure in acetic anhydride to obtain a compound 6; carrying out reduction and ring opening by utilizing NaBH4 to obtain a mixture of position isomerism compounds 7A and 7B; carrying out the ring closure in the presence of iodomethane and potassium carbonate to generate position isomerism lactone 8A and 8B; step 8, reducing the 8A, obtained by column passing separation, by utilizing DIBAH (Diisobutylaluminum Hydride) to obtain a compound 9; carrying out Wittig reaction to obtain a compound 10; carrying out Michael addition under an alkaline condition to obtain a compound 11; finally, hydrolyzing the compound 11 under the alkaline condition to obtain a final compound.

The invention relates to a preparation method of 2-((1S3aR7aR)-5-tert-butyloxycarbonyltetrahydrofuro[3,4]piperidine-1)acetic acid. The preparation method comprises 11 steps: carrying out esterification on a dicarboxylic acid piperidine compound 1 in thionyl chloride to obtain a diester compound 2; then reducing a pyridine ring by utilizing palladium carbon to obtain a compound 3; then taking the compound 3 to react with Boc acid anhydride to obtain a Boc protected compound 4; hydrolyzing the compound 4 by utilizing lithium hydroxide to obtain a dicarboxylic acid compound 5; carrying out ring closure in acetic anhydride to obtain a compound 6; carrying out reduction and ring opening by utilizing NaBH4 to obtain a mixture of position isomerism compounds 7A and 7B; carrying out the ring closure in the presence of iodomethane and potassium carbonate to generate position isomerism lactone 8A and 8B; step 8, reducing the 8A, obtained by column passing separation, by utilizing DIBAH (Diisobutylaluminum Hydride) to obtain a compound 9; carrying out Wittig reaction to obtain a compound 10; carrying out Michael addition under an alkaline condition to obtain a compound 11; finally, hydrolyzing the compound 11 under the alkaline condition to obtain a final compound.

The invention relates to a preparation method of 1-phenylmethyl-5-(tert-butyloxycarbonyl) octahydropyrrolopyrrole-2-carboxylic acid, and mainly solves the technical problem that no suitable industrialsynthesis method exists at present. The method comprises the following four steps: 1, adding triethylamine into anhydrous toluene to obtain a compound 2 from a compound 1 and ethyl phenylmethylglycinate; 2, dissolving the compound 2 in glacial acetic acid under the action of hydrobromic acid acetate to obtain a compound 3; 3, dissolving the compound 3 in methanol, and adding Boc anhydride to obtain a compound 4; and 4, dissolving the compound 4 in water and methanol, adding sodium hydroxide, and hydrolyzing to obtain a compound 5, wherein the reaction formula is shown in the specification.

The invention relates to a preparation method of (2,4,5,7-tetrahydropyrano[3,4-c]pyrazol-7-yl)methanol, which mainly solves the technical problem that there is no suitable industrial synthesis method at present. The present invention is divided into ten steps: first, compound 1 and triethyl orthoformate generate compound 2 under the action of boron trifluoride ether, then react with benzylhydrazine to obtain compound 3, and react with acetyl chloride to obtain compound 4, then obtain compound 4 in two Add N-bromosuccinimide to the solution of methyl chloride to obtain compound 5, react with ethylene boron trifluoride potassium salt to obtain compound 6, and obtain compound 7 with sodium hydroxide, and obtain compound 7 with N-bromosuccinimide Compound 8 was obtained by the reaction, compound 9 was obtained under the action of methanesulfonic acid, compound 10 was obtained by reacting with silver nitrate in acetonitrile solution, and product 11 was obtained by reacting with hydrogen gas under the catalyst palladium carbon. The compounds obtained in the present invention are useful intermediates or products of many pharmaceutical synthesis.

The invention discloses a method for synthesizing a compound ticagrelor and a synthesized intermediate thereby. The method comprises the following steps: carrying out a substitution reaction between a compound (2) and a compound (3) to prepare a compound (4); carrying out a reduction reaction on the compound (4) to prepare a compound (5); carrying out a chlorination reaction on the compound (5) to prepare a compound (6); carrying out a substitution reaction between the compound (6) and a compound (7) to prepare a compound (8); and finally, carrying out a hydroxyl deprotection reaction on the compound (8), thereby obtaining the ticagrelor (1). The reaction formulas are as shown in the specification. The invention provides a novel method for synthesizing ticagrelor. The synthetic method has the advantages of novel technical route, simple and convenient operation, high synthesis yield, high product purity, cheap and readily available raw materials and the like, and is suitable for industrialized production. Meanwhile, the synthesized ticagrelor intermediate provides a novel intermediate raw material for preparation of the ticagrelor.

The invention relates to a tert-butylhexahydro-2H-pyrrole[1,4]oxazepine-7(3H)-carboxylic ester preparation method. A purpose of the invention is mainly to solve the technical problem of no industrialsynthesis method in the prior art. According to the invention, the method comprises the following six steps: generating a compound 2 from a compound 1 and N-benzyl hydroxylamine under the action of potassium acetate, 2, carrying out ring opening under the action of raney nickel to obtain a compound 3, carrying out a reaction on the compound 3 and chloroacetyl chloride to obtain a compound 4, obtaining a cyclization product compound 5 under the action of potassium tert-butoxide, carrying out borane reduction to obtain a compound 6, and finally obtaining a target product compound 7 under the action of palladium carbon. According to the invention, the compound obtained by the method is a useful intermediate or product for synthesizing a lot of medicines.

The present invention relates to an intermediate of (2S,3R)-3-substituted phenylpyrrolidine-2-carboxylic acid and its preparation method and application, mainly solving the problem of (2S,3R)-3-substituted phenylpyrrolidine-2-carboxylic acid 2‑Carboxylic acids have no technical problems amenable to industrial synthetic methods. The present invention uses compound II and halogenated benzene as raw materials, and under the action of organometallic reagents, it is prepared through successive reaction steps such as Michael addition reaction, reduction reaction, debenzylation reaction, Boc protection reaction, oxidation and removal of Boc protection group, etc. Compound I ((2S,3R)-3-substituted phenylpyrrolidine-2-carboxylic acid) is obtained. The method is convenient to operate, stable in yield and suitable for large-scale production.

The invention relates to a preparation method of (3aR, 7S, 7aR)-tertiary butyl 7-hydroxyhexahydrofuro-[3,2-b] pyridine-4(2H)-carboxylic ester, and mainly solves the technical problem of no method suitable for industrial synthesis currently. The preparation method disclosed by the invention comprises nine steps in total; in the ninth step, under the action of sodium borohydride, a pair of compounds 12 and 12A are obtained. ( The structural formulas of the compounds are shown in the description) The compounds obtained by the preparation method are useful intermediates or products synthesized by various medicaments.

The invention relates to a synthesis method of 4-(tert-butoxycarbonyl) octahydrofuro[3,2-b]pyridine-6-carboxylic acid, and mainly solves the technical problem that there is no suitable industrial synthesis method at present. The present invention is divided into six steps, firstly, compound 2 is obtained by esterification of compound 1, then compound 3 is obtained by reacting with iodine, compound 4 is obtained after acetylation of compound 3, compound 5 is obtained by coupling again, compound 6 is obtained by ring closure, and compound 6 is obtained by hydrogenation 7, and then reacted with Boc anhydride to obtain compound 8, which was hydrolyzed to obtain the final compound 9. The reaction formula is as follows: .

The invention discloses a synthesis method of a ticagrelor intermediate. The method comprises the steps of allowing a compound (2) and a compound (3) to perform a coupling reaction to form a compound (4), and allowing the compound (4) to perform a rhodium-catalyzed asymmetric ternary cyclization reaction to form a ticagrelor intermediate compound (1), wherein a reaction formula of the method is shown in the description. The synthesis method has the advantages that the method is novel in technical route, easy and simple to operate, high in synthesis productivity and suitable for industrial production, a product is high in purity, and raw materials are cheap and easy to obtain. The compound (1) prepared by the rhodium-catalyzed asymmetric ternary cyclization reaction is a novel catalytical system; the novel system has the characteristics of mild reaction conditions, simple post-treatment, lower overall cost, relatively easy amplification of the reaction and the like; at the same time, the synthesized ticagrelor intermediate provides an intermediate raw material for preparation of ticagrelor and serves as an important intermediate for synthesis of ticagrelor.

The invention relates to a method for preparing 1-benzyl-5-(tert-butoxycarbonyl) octahydropyrrolopyrrole-2-carboxylic acid, which mainly solves the technical problem that there is no suitable industrial synthesis method at present. The present invention is divided into four steps. In the first step, at first compound 2 is obtained by adding triethylamine into anhydrous toluene with compound 1 and benzylglycine ethyl ester. In the second step, compound 2 is dissolved in glacial acetic acid in acetic acid hydrobromic acid Compound 3 is obtained under the action of the third step. Compound 3 is dissolved in methanol, and then Boc anhydride is added to obtain compound 4. In the fourth step, compound 4 is dissolved in water and methanol, and sodium hydroxide is added to be hydrolyzed into compound 5. The reaction formula is as follows: .

The invention relates to a preparation method of tertiary butyl 1-hydroxyl-8-azaspirane[4,5]decane-8-carboxylic ester and mainly solves the technical problems that a method suitable for industrial synthesis does not exist at present. The preparation method comprises three steps: firstly, generating a compound 2 by a compound 1 under the action of hydrochloric acid; secondly, obtaining a compound 3 by enabling the compound 2 to react with di-tert-butyl dicarbonate in a mixed solution of dioxane and water under the existence of sodium carbonate; finally, obtaining a product 4 by treating the compound 3 through sodium borohydride, wherein a reaction formula is as shown in the description. The tertiary butyl 1-hydroxyl-8-azaspirane[4,5]decane-8-carboxylic ester obtained through the preparation method disclosed by the invention is a useful intermediate or a product compounded by many medicines.

The invention relates to a preparation method of 2-(1-(tertbutyloxycarbonyl)azacyclobutyl-3-yl)cyclopropanecarboxylic acid. The preparation method solves the problem that the existing appropriate 2-(1-(tertbutyloxycarbonyl)azacyclobutyl-3-yl)cyclopropanecarboxylic acid industrial synthesis method does not exist. The preparation method comprises that 1, a compound 1 and iodomethane undergo a reaction under alkaline conditions to produce a compound 2, 2, the compound 2 is treated by sodium borohydride to form a compound 3, 3, the compound 3 is oxidized by Dess-Martin periodinane to form a compound 4, 4, the compound 4 and a compound 5 undergo a reaction to produce a compound 6, 5, the compound 6 and trimethylsulfoxonium iodide undergo a reaction to produce a compound 7, and 6, the compound 7 is hydrolyzed under alkaline conditions to form an end product compound 8. The reaction equation is shown in the following description. The 2-(1-(tertbutyloxycarbonyl)azacyclobutyl-3-yl)cyclopropanecarboxylic acid is a useful intermediate or product for synthesis of many drugs.