15 results about "Mitsunobu reaction" patented technology

Four-arm polyethylene glycol amine and preparation method and application thereof, relate to the technical field of high polymer materials, and solve the problem of poor comprehensive performance such as strength, fatigue resistance and swelling resistance when the traditional double network hydrogel is applied to the preparation of cartilage repair materials in the prior art. The four-arm polyethylene glycol amine provided by the application has a molecular weight of 10 kDa or 40 kDa. Four-arm polyethylene glycol, phthalimide, diisopropyl azodicarboxylate and triphenylphosphine are subjected to Mitsunobu reaction and hydrazinolysis to obtain four-arm polyethylene glycol amine with a molecular weight of 10 kDa. Four-arm polyethylene glycol, phthalimide, diisopropyl azodicarboxylate and triphenylphosphine are subjected to Mitsunobu reaction and hydrazinolysis to obtain four-arm polyethylene glycol amine with a molecular weight of 40 kDa. The double network hydrogel prepared from the four-arm polyethylene glycol amine has excellent comprehensive performance such as high mechanical strength, fatigue resistance, self-recovery and swelling resistance, and can be applied to the preparation of cartilage-like materials.

The invention discloses a synthesis method of 2 '-O-methyladenosine, and belongs to the technical field of nucleoside synthesis and medicinal chemistry. According to the method, xylose which is rich in source is taken as an initial raw material, eight-step reaction including acetalation protection, acetylation, glycosylation, deacetylation, methylation, deacetalation protection, Mitsunobu reaction and secondary deacetylation is performed, reaction conditions of each step are accurately controlled, and finally, a target product is synthesized. The method has the advantages of high methylation reaction regioselectivity, mild reaction conditions, cheap and easily available raw materials and controllable cost, and overcomes the problems of poor methylation reaction regioselectivity, harsh reaction conditions and high cost in the existing synthesis method. The obtained product has important application value in the fields of research and development of antiviral drugs, design of nucleic acid probes and the like.

The present invention relates to a method for preparing a compound of formula I, which is a key intermediate of maralixibat chloride, and a use thereof. The compound of formula I can be synthesised by using a compound of formula IV or a compound of formula IX as a starting substrate, wherein the compound of formula IX undergoes a Mitsunobu reaction with a compound of formula VIII and sulfhydryl deprotection and substitution reactions to obtain the compound of formula IV, and the compound of formula IV then undergoes in sequence a reduction reaction and two oxidation reactions to obtain the compound of formula I, wherein R1, R4, and R5 are as defined in the description. The present invention provides a new method for synthesising a compound of formula I as a key intermediate of maralixibat chloride from different starting substrates; the method of the present invention has the advantages of simple steps, inexpensive raw materials, mild reaction conditions, high total yield, and high product purity, and is suitable for industrial production.

This invention discloses a apigenin-betaine compound and its preparation method. The compound uses apigenin (Api) as its core, with -O-(CH2) at the 7', 4', and / or 5-position hydroxyl groups. n -N + (CH3)2-CH2COO ‑ Fragment substitution (n=2~12, x=1~3) forms an internal salt-type zwitterionic structure. In preparation, apigenin is first reacted with bromool Br(CH2). n A mitsunobu reaction was performed on OH under triphenylphosphine / dialkyl azodicarbonate conditions to obtain mono / polysubstituted bromoalkoxylated apigenin; subsequently, nucleophilic substitution with N,N-dimethylglycine under alkaline conditions yielded the target product. This structure, possessing both a tunable alkyl chain and a betaine cation / anion pair, significantly enhances the solubility and hydration capacity of apigenin in aqueous / alcoholic media, strengthens its affinity and stability for biomembranes, thereby improving in vivo absorption and distribution and potentially maintaining its antioxidant and anti-inflammatory activities. The method is mild, with a wide solvent and temperature range, suitable for scale-up and formulation applications.

The application discloses a trifluoromethyl benzyl ether substituted amino acid derivative, a preparation method and application thereof, and belongs to the technical field of organic compound synthesis and medicine. The synthesis method of the trifluoromethyl benzyl ether substituted amino acid derivative is obtained through two-step reaction, that is, first, a photo extension reaction is carried out between a benzyl alcohol compound and hydroxynaphthaldehyde (or hydroxybenzaldehyde), then a Schiff base is formed after an amino acid ester hydrochloride, and then the Schiff base is reduced by sodium cyanoborohydride, and then simple hydrolysis is carried out to obtain the trifluoromethyl benzyl ether substituted amino acid derivative. The preparation method has the characteristics of simple steps, mild reaction conditions and fast reaction, and meets the requirements of green chemistry. The compound prepared according to the method can selectively adjust S1P1 receptors without exciting S1P3 receptors, and is expected to be developed into a new preparation for treating idiopathic pulmonary fibrosis.

This invention belongs to the field of medicinal chemistry and pharmaceutical technology, specifically relating to a method for preparing a rufiamide impurity reference standard. The method includes the following steps: (1) mixing o-fluorobenzyl alcohol, 1H-1,2,3-triazol-4-nitrile, photocatalytic reaction reagent, triphenylphosphine, and solvent 1, and reacting to obtain 1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-nitrile; (2) mixing 1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-nitrile, carbonate, hydrogen peroxide, and solvent 2, and reacting to obtain 1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-formamide. This invention is simple to operate, has milder reaction conditions, and does not involve the use or generation of azides; the synthesis method is green and novel, and can rapidly and efficiently prepare 1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-formamide.

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.

The present invention belongs to the field of pharmaceutical intermediates. Provided in the present invention is a scale-up preparation method for tert-butyl (3aR,5S,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate methanesulfonate. The method comprises: subjecting tert-butyl cis-5-oxohexahydrocyclopenta[C]pyrrole-2(1H)-carboxylate and a reducing agent, which serve as raw materials, to a reaction in an organic solvent to obtain intermediate 1; subsequently, subjecting the intermediate to a Mitsunobu reaction with CH 3NHCbz to obtain intermediate 2; and finally, performing palladium-on-carbon catalyzed hydrogenation, followed by salt formation with methanesulfonic acid to obtain the product tert-butyl (3aR,5S,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate methanesulfonate. The method reduces raw material costs, has a simple and reliable process with easy industrialization, and provides a new reaction route for the synthesis of tert-butyl (3aR,5S,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate methanesulfonate.

The application belongs to the technical field of medicine synthesis, and particularly relates to an intermediate compound of edoxaban. The application takes 2-bromo-5-methyl-3a, 4, 5, 6, 7, 7a-hexahydrothiazolo[5, 4-c] pyridine as a starting material, and a lactam product is obtained by undergoing a carbonylation reaction with (3R, 4R)-3-amino-4-hydroxy-N, N-dimethylcyclohexane-1-carboxamide under the action of a catalyst, and the obtained lactam product undergoes a Mitsunobu reaction with N-(4-chlorophenyl) oxamide to obtain edoxaban. The preparation method of edoxaban provided by the application introduces a lactam by using a copper-catalyzed carbonylation reaction, and the whole synthesis method is simple in operation, high in reaction yield and purity; can effectively avoid the addition of n-butyllithium and low-temperature operation required by the carboxylation in the prior art, improve the operation safety, and has the advantages of mild use conditions, high conversion rate and simple operation.

The application discloses a trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative, a preparation method and application thereof, and belongs to the technical field of organic compound synthesis and medicine. The synthesis method of the trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative is obtained through two-step reaction, that is, first, a light extension reaction is carried out on a benzyl alcohol compound and hydroxynaphthaldehyde (or hydroxybenzaldehyde), then a Schiff base is generated after the amino acid ester hydrochloride (or amino sulfonic acid, or amino phosphoric acid) is reacted with the benzyl alcohol compound, and sodium cyanoborohydride is used for reduction (or simple hydrolysis is carried out after reduction), so the trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative is obtained. The preparation method has the characteristics of simple steps, mild reaction conditions and fast reaction, and meets the requirements of green chemistry. The compound prepared according to the method can selectively adjust S1P1 receptors without exciting S1P3 receptors, and is expected to be developed into a new preparation for treating inflammatory and immune related diseases such as pulmonary fibrosis, ulcerative colitis and multiple sclerosis.

A method for performing Mitsunobu reaction between an alcoholic hydroxyl group donor and an active hydrogen donor, comprising the following steps: reacting the alcoholic hydroxyl group donor and the active hydrogen donor with a trihydrocarbylphosphine reagent and an azodicarboxylate reagent in the presence of an organic solvent, wherein the organic solvent is a linear or branched alkane containing 8 to 16 carbon atoms.

The invention relates to a preparation method of an entecavir EP impurity D. The preparation method comprises the following step: in an organic solvent, carrying out Mitsunobu reaction on a compound shown as a formula I and a compound shown as a formula II to prepare a compound shown as a formula III. And hydrolyzing the compound in the formula III under an alkaline condition to prepare the entecavir EP impurity D (a compound in a formula IV). The preparation method provided by the invention has the advantages of short synthetic route, simple operation, mild reaction conditions and high product purity, and provides a basis for quality research of entecavir.

The invention discloses a preparation method of optically pure glabridin. In particular to a preparation method of a compound VII, which comprises the following step: in a solvent, in the presence of a phosphine reagent and an azo reagent, carrying out a Mitsunobu reaction on a compound V and a compound VI to generate the compound VII. The preparation method has the advantages of cheap and easily available raw materials, mild reaction conditions and high total yield, and is beneficial to industrialization of optically pure glabridin.

The application discloses a full synthesis method of cephinold H and fortalpinoid C, comprising the following steps: taking natural product cephanolide B as a raw material, carrying out oxidative de-arrangement and acetylation to obtain a dienone compound, then carrying out ring expansion rearrangement to obtain natural product cephinold H as a secondary product, then introducing an occupying group (Br or Cl atom) to improve the regioselectivity of the ring expansion rearrangement, so that a ring expansion product substituted with a halogen atom (Br or Cl atom) is obtained in a high proportion, then removing the halogen atom (Br or Cl atom) under a palladium catalytic reduction condition to obtain natural product cephinold H, then oxidizing cephinold H by selenium dioxide and reducing by sodium borohydride to obtain natural product fortalpinoid C with opposite configuration, and finally inverting the configuration of the hydroxyl group through a Mitsunobu reaction, so that the chemical synthesis of fortalpinoid C is realized, and the synthesis route has the advantages of simplicity, high efficiency, simple operation, low cost and the like, and is suitable for the mass synthesis of cephinold H and fortalpinoid C, and provides an important material basis for the bioactivity evaluation of the two products.