33 results about "HATU" patented technology

The invention discloses a preparation method for carfilzomib. The method utilizes HATU as a condensing agent to perform condensation and comprises a plurality of steps. The method has the characteristics of short reaction time, simple feeding, no need for nitrogen protection, appropriate control the feeding temperature, no need for strict temperature control, and easier washing and removal of the by-product of HATU, greatly shortens the preparation time, and improves the work efficiency, thus being suitable for industrial production.

The invention relates to a preparation method for an organic electrode material based on a polyimide structure. The preparation method comprises the steps: under the nitrogen protection, dispersing anorganic conductive agent into a solvent, adding HATU and diamine monomer to perform stirring reaction and filtering, washing and vacuum drying to obtain an amination conductive agent; ultrasonicallydispersing into a solvent, then sequentially adding diamine monomer, dianhydride monomer and a catalyst to perform stirring reaction and cooling, filtering, washing and vacuum drying to obtain powder;performing thermal treatment under the inert atmosphere to obtain the organic electrode material based on the polyimide structure. When the organic electrode material is utilized as a lithium ion battery anode material, the electrochemical characteristics of high magnification and high cyclic stability are achieved. By means of the preparation method, an efficiency of active matters in the electrode material to participate a charge-discharge process is improved; thus, industrial production cost is reduced, and very large potential and industrial value are achieved.

The invention discloses a cyclo(Phe-Pro-lle-Phe-Pro-Pro-Leu-Val)peptide preparation method. The preparation method comprises 1) contacting a matrix resin, Fmoc-Phe-OH and DIPEA in a solvent for a reaction to obtain a primary resin, removing Fmoc through methanol end blocking and elution and carrying out piperidine deprotection to obtain a secondary resin, 2) carrying out continuous modification onthe secondary resin orderly with a plurality of modified amino acids multiple times to obtain a tertiary resin, wherein each modification reaction process comprises that the resin and the modified amino acids contact and undergo reactions in the presence of DIPEA, a solvent and HATU, removing Fmoc through elution and carrying out piperidine deprotection, 3) removing the resin group in the tertiary resin through a resin eluent so that linear octapeptide is obtained, and 4) carrying out liquid phase cyclization on the linear octapeptide in the presence of a solvent, PyBOP, HOBt and DIPEA to obtain cyclopeptide. The preparation method realizes synthesis of cyclopeptide.

The invention discloses an aryl nitrogen mustard-domide conjugate and a preparation method and pharmaceutical application thereof. Compound (1) is subjected to reaction with compound (2) in the presence of polypeptide condensing agents EDCI and DMAP, or HATU and DIPEA to obtain compound I that is used to prepare antitumor drugs. The two drugs of different target types are combined herein to form aprodrug; multi-action synergic antitumor effect is achieved; antitumor activity and tolerance are improved; drug resistance of tumors is decreased. The domide drugs are linked via amido bonds, so that chances for amino groups on domide benzene rings to be degraded by in-vivo enzymes can be slimmed, and in-vivo bioavailability of the drugs is improved.

The invention provides a preparation method of a novel natural active polypeptide Tubulysin U. The preparation method comprises the following steps: dissolving a compound 2 in trifluoroacetic acid, heating under reflux to prepare an intermediate, reacting with a compound 3 and diisopropylethylamine to obtain a product, reacting the product with 2, 6-dimethylpyridine and tert-butyldimethylsilyltrifluoromethanesulfonate, adding sodium hydroxide after the reaction to prepare an intermediate acid, reacting the intermediate acid with a compound 6, HATU and diisopropylethylamine to obtain a product,adding triphenylphosphine to prepare an intermediate amine, adding a compound 8 and HATU to react, adding ammonium fluoride to prepare a first intermediate, adding sodium hydroxide to the first intermediate to prepare a second intermediate, adding acetic anhydride to the second intermediate to prepare a third intermediate, adding trifluoroacetic acid to the third intermediate to prepare a fourthintermediate, and adding formaldehyde and sodium cyanoborohydride to the fourth intermediate to react, thereby obtaining the target product. The structures of the compound 2, compound 3, compound 6 and compound 8 are disclosed in the specification.

The invention discloses a solid-phase preparation method for an exenatide crude product. The method comprises the following steps of: taking solid-phase synthetic resin as a starting material; sequentially connecting amino acids or polypeptides with Fmoc protecting groups according to a solid-phase synthesis method, so as to obtain the protected nonatriaconta-peptide resin; sequentially removing the Fmoc protecting groups during the process; taking any one of TBTU/HOBt, HBTU/HOBt, BOP/HOBt, HBTU/HOAt, HBTU/HOAt, DIC/HOBt or BOP/HOAt as a condensing agent, and performing peptide grafting reaction to obtain the protected nonatriaconta-peptide resin; and synchronously removing side-chain protecting groups and cutting peptide to obtain the exenatide crude product. The steps have the following characteristics that: 1, the polypeptides with the Fmoc protecting groups are Fmoc-Gly-Gly-OH; and 2, synthesis for residue 20-19 and residue 17-11 is performed by taking HATU/HOBt as a condensing agent.

The invention relates to a method for synthesizing drug polypeptide nafarelin with a microwave solid-phase synthesis method. According to the solid-phase synthesis method, a raw material is sequentially connected with Fmoc (fluorenylmethoxy carbony) protected amino acids through a microwave reaction instrument, protective decapeptide resin is obtained, meanwhile, Fmos protecting groups are removed sequentially, one of DIC/HOBt, DIC/HOAt, BOP/HOBt, BOP/HOAt, HBTU/HOBt, HBTU/HOAt, HATU/HOBt, HATU/HOAt and HCTU/HOBt is taken as a condensing agent for a peptide synthesis reaction, side chain protecting group removing and peptide cutting are performed synchronously after the protective decapeptide resin is obtained, a crude product of nafarelin is obtained, the crude product is separated and purified by a C18 chromatographic column, the nafarelin is obtained and then subjected to freeze drying, and accordingly, a nafarelin acetate or trifluoroacetate product is obtained.

The invention discloses a liquid-phase synthesis method of snake venom-like tripeptide. The method comprises the following steps: using raw materials Fmoc-Da (Boc)-OH, benzylamine, Boc-beta-Ala-OH andH-Pro-OMe. HCl/H-Pro-OBzl. HCl as raw materials and DIC/HOBt, DIC/HOAt, EDC/HOBT, HATU, HBTU and the like as reagents, synthesizing polypeptide H-beta-Ala-Pro-Dab(Boc)-NHBzl, then cutting off a protective group Boc under an acidic condition and purifying to obtain the product. The product H-beta-Ala-Pro-Dab(Boc)-NHBzl is directly obtained by using a solid-phase synthesis method, the stability problem of CTC resin is solved in the product, the racemization problem of Dab is avoided by adopting a method of connecting Fmoc-Db (Boc)-OH and benzylamine, and the synthesis method is short in processroute, very short in production period, suitable for large-scale production, good in method stability and suitable for large-scale production.

The invention relates to a synthesis method of tamibarotene, which comprises the steps of: 1)taking aniline and monomethyl ester terephthalate as raw materials, and synthesizing p-carbaniloyl methyl benzoate (III); 2) under the protection of nitrogen in an anhydrous condition, carrying out cyclization on the intermediate III and 2, 5-dimethyl-2, 5-hexanediol at a low temperature, to obtain an intermediate II; and 3) hydrolyzing the intermediate II to obtain the tamibarotene (I), wherein dicyclohexyl carbodiimide (DCC)/ hydroxyl benzotriazole (HOBt), diisopropylcarbodiimide (DIC)/ HOBt, HATU or HBTU taken as a condensing agent as well as triethylamine and diisopropylethylamine (DIEA) taken as acid-binding agents can be added into the step 1); halogen acid taken as a catalyst is added into the step 2); and the reaction solvent is halogenated alkanes. The synthesis method of the tamibarotene avoids the link with high pollution, thus reducing the environmental cost.

The invention discloses a liquid-phase synthesis method of palmitoyl tripeptide-1. The method comprises the following steps: synthesizing polypeptide Pal-Gly-His-Lys-OH by taking raw materials Boc-Lys(Z)-OH, MS-OH, Boc-His-OH and Boc-Gly-OH as raw materials and taking DIC/HOBt, DIC/HOAt, EDC/HOBt, HATU, HBTU and the like as reagents; then cutting off a protecting group Boc under an acidic condition; and purifying to obtain a product. The product is obtained by the liquid-phase synthesis method disclosed by the invention; the product is obtained by utilizing simple and conventional reactions in a process; each step of reaction is easy to detect and control; a key intermediate is easy to separate and store; and after hydrogenation, a high-purity product can be obtained without purification.The liquid-phase synthesis method is suitable for industrial large-scale production.

The invention relates to a preparation method of N-phenyl bis (trifluoromethanesulfonyl) imine, and belongs to the technical field of chemical engineering. The method comprises the following steps: dissolving trifluoromethanesulfonic acid and organic alkali in an organic solvent, and adding HATU for reaction; the reaction temperature is greater than or equal to 15 DEG C, and the organic solvent is not boiled; after the reaction is finished, a reaction solution containing trifluoromethanesulfonic acid active ester is obtained; adding aniline into the reaction liquid, and reacting at 25 +/-5 DEG C for 6-12 hours; and after the reaction is finished, removing the organic solvent to obtain a crude product containing the N-phenyl bis (trifluoromethanesulfonyl) imine, washing, and recrystallizing and purifying by using an alcohol solvent with 1-3 carbon atoms to obtain the N-phenyl bis (trifluoromethanesulfonyl) imine. The N-phenyl bis (trifluoromethanesulfonyl) imine with high purity and high yield can be prepared by the method, the reaction condition is mild, the utilization rate of raw materials is high, and the method is green and environment-friendly.

The invention provides a method for preparing a compound Lifitegrast. The method comprises the following steps of under the action of an alkali, carrying out a reaction on a compound V and HATU to generate a compound VI, optionally separating out the compound VI, reacting the compound VI with a compound III, and after the reaction is finished, carrying out post-treatment to obtain the compound Lifitegrast, wherein the reaction equation is defined in the specification. According to the invention, reaction raw materials adopted by the preparation method do not need to be subjected to protectionand deprotection steps, so that the preparation method is short in reaction route, high in reaction efficiency, low in price of the reaction raw materials and suitable for industrial production; and the single-step yield of the reaction is 80% or above, the total yield of the reaction is remarkably increased, and the product purity is 99% or above.

The invention belongs to the technical field of nano materials, and particularly relates to AlP quantum dots and a preparing method thereof. The preparing method includes the steps that aluminum chloride hexahydrate and a phosphorus source are subjected to solvothermal reaction in organic solvent to obtain the AlP quantum dots which are small in size distribution and high in crystallinity degree and are distributed uniformly, wherein the phosphorus source is selected from one or two of tri-o-methylphenylphosphine, triphenylphosphine, phosphorus pentachloride and HATU and [BMIM]PF6. The synthesis method is easy to operate, mild in reaction and high in repeatability; the obtained quantum dots have strong fluorescence-emission in the blue light region after being irradiated with ultraviolet light, can serve as a blue light emitter applied to a light-emitting diode and can also be applied to biomarking and imaging. In addition, the fluorescence Stock displacement of the quantum is large, interference to transmission signals by exciting light can be effectively avoided, and the quantum dots have extraordinary potential advantages in developing novel optoelectronic devices in the future.

The invention discloses a method which is used for preparing an Atazanavir monomer and applied in the technical field of drug synthesis. The method comprises the steps that N-methoxycarbonyl-L-tertiary leucine and 1-[4-(pyridine-2-yl)-phenyl]-4(S)-hydroxyl-5(S)-2,5-diamido-6-phenyl-2-aza-hexane are subjected to an amidation reaction by taking HATU as a condensing agent under the condition of organic alkali and an organic solvent, certain aftertreatment is conducted, and then the Atazanavir monomer is obtained. According to the method, the synthetic yield of Atazanavir is increased, the purity is high, and the cost of raw materials is effectively reduced; meanwhile, the reaction time is short, material putting is easy, nitrogen protection is not needed, the material putting temperature can be properly controlled, by-products of HATU can be washed off more easily, the preparation time is greatly shortened, the working efficiency is improved, and therefore the method is suitable for industrial production.

The invention discloses a fluorescent probe for detecting pyroglutamamide aminopeptidase I as well as a preparation method and application thereof. The method comprises the following steps: mixing LXY, HATU and DIPEA, completely dissolving the mixture in a dry dichloromethane solution, and carrying out a stirring reaction at 0 DEG C; then adding a TPAN solution, further conducting stirring and reacting at room temperature, and carrying out purifying after the reaction is finished so as to obtain a dark red solid BH1-BOC; dissolving BH1-BOC in anhydrous dichloromethane, adding a prepared trifluoroacetic acid solution under an ice salt bath condition, and carrying out room-temperature stirring reaction after dropwise adding is completed; spin-drying a solvent, adding dichloromethane, and repeating the above operations multiple times until the trifluoroacetic acid is completely spin-dried; and purifying a crude product to obtain a red solid BH1.

Disclosed is a preparation method of medicine RIP1183 for resisting multi-drug resistance staphylococcia. Any one of Rink, AmideMBHA Resin, MBHA Resin and Rink Amide-AM Resin is adopted as a starting raw material, on the basis of a solid-phase synthesis method, according to a RIP1183 amino acid sequence, corresponding amino acids with Fmoc protection are connected in sequence, Fmoc protecting groups are removed in sequence in the process, one of DIEA/HOBt or DIEA or TBTU/HOAt/HOBt or HBTU/HOBt or HBTU/HOAt or HATU/HOBt or HATU/HOAt or HCTU/HOBt is adopted as a condensing agent for performing a transpeptidase reaction, aftr corresponding RIP1183 resin is obtained, meanwhile, side chain removal protecting groups and final peptide cut-off are performed, a crude RIP1103 product is obtained, and separation and purification are performed through a C18 or C8 chromatographic column to obtain the needed purified RIP1183 product.

The invention provides a synthesis method of (E)-4-(benzenesulfonyl) butyl-3-olefine acid, which comprises the following steps: 1) taking 8-aminoquinoline and 3-butenoic acid as raw materials, taking dichloromethane as a solvent, and obtaining a compound 3: N-(quinoline-8-yl) butyl-3-enamine under the action of HATU and 2, 4, 6-trimethylpyridine; 2) taking acetonitrile as a solvent, and reacting the compound 3 with sodium benzenesulfinate under the action of palladium acetate, benzoic acid and silver hexafluoroantimonate to obtain a compound 5: (E)-4-(benzenesulfonyl)-N-(quinoline-8-yl) butyl-2-enamine; and 3) hydrolyzing the compound 5 under the action of an HCl aqueous solution. The method comprises the following steps: carrying out dehydration condensation on 3-butenoic acid and 8-aminoquinoline to obtain amide; under the catalysis of palladium, olefinic bonds in the amide react with sodium benzenesulfinate to obtain allyl sulfone; amido bonds in allyl sulfone are hydrolyzed under the acidic condition, meanwhile, double bonds are shifted, and a target product is obtained and has excellent regioselectivity.

The invention discloses a synthesis method and application of a Fe (II)-based specific MRI contrast agent, and the synthesis method comprises the following steps: carrying out a reaction on tBut-DOTAGA, N, N-diisopropylethylamine DIPEA, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate HATU and 5-hydroxy-2-adamantanone to synthesize a first compound; performing reaction synthesis on the first compound, a pyridine solution and methoxy ammonia hydrochloride to obtain a second compound; introducing ozone gas into the second compound under an anaerobic condition, and carrying out column separation to obtain a third compound Fer-DOTA; and stirring the third compound and trifluoroacetic acid (TFA) for reaction, adjusting the pH value, adding gadolinium chloride GdCl3 for stirring reaction, and performing high performance liquid chromatography separation to obtain the Fe (II)-based specific MRI contrast agent. Gd-DOTA is covalently bound to a Fe (II) selective group through a chemical bond, so that the Gd-DOTA has Fe (II) selective enrichment capacity, Fe (II) responsive enrichment of Gd-DOTA is realized, and the contrast agent concentration and T1WI signal intensity of a Fe (II)-rich tissue are improved in a targeted manner, so that spatial and temporal distribution of Fe (II) in an ICH edema region is established, and quantitative MRI imaging of Fe (II) is realized.

The invention belongs to the technical field of drug synthesis, and particularly relates to a synthetic route of a compound and application of the compound in the field of preparation of anti-diabeticdrugs. The invention provides a synthetic route of SN158, and also provides the application of the synthetic route in the field of preparation of anti-diabetic drugs. The synthetic route of the invention comprises the following steps: brominating a raw material, namely 2,4-dihydroxybenzaldehyde; protecting para-hydroxyl groups by using methoxymethyl groups; methylating ortho-hydroxyl groups by using dimethyl sulfate or methyl iodide; and carrying out a Claisen-Schmidt condensation reaction by using a hydrochloric acid ethanol or boron trifluoride diethyl ether solution, with HATU or EDCI andHOBt as coupling agents for an amidation reaction. According to the invention, the yield of the prepared SN158 can reach 60% or above; meanwhile, column chromatographic purification is not needed in the preparation process, and the finally produced compound with a purity of 99% or above can be obtained only through recrystallization; and the method is suitable for large-scale/industrial productionand overcomes the technical defects that SN158 is low in synthesis yield and complex in purification in the prior art.

The invention relates to the technical field of medicinal chemistry, and particularly discloses oat bran phenolic amide alkaloid, a preparation method thereof and application of the oat bran phenolic amide alkaloid in preparation of itching relieving products. The oat bran phenolic amide alkaloid has a structure as shown in a formula I or a formula II. The preparation method of the oat bran phenolic amide alkaloid specifically comprises the following steps: taking a reaction substrate caffeic acid analogue, adding an organic solvent, adding 4-(2-aminoethyl) phenol and triethylamine while stirring, and adding HATU after 3-6 minutes; after charging is finished, continuously reacting for 3-6 hours at room temperature, and monitoring disappearance of the reaction raw materials by TLC (thin layer chromatography); and stopping stirring, carrying out reduced pressure distillation on the reaction system to remove the solvent, and carrying out silica gel column chromatography purification on residues to obtain the oat bran phenolic amide alkaloid. Researches show that the oat bran phenolic amide alkaloid or the composition thereof disclosed by the invention has an excellent itching relieving effect; therefore, the oat bran phenolic amide alkaloid or the composition thereof can be used for developing antipruritic products.