cas 936563-96-1, Ibrutinib | Articles data

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A synthetic method of ibutinib
The present invention provides a preparation method of ibutinib and its application, by optimizing the feeding ratio and reaction conditions, increasing the purification step of the intermediate, and the use of inorganic alkali instead of organic base as an acid binding agent, significantly reducing the impurity content of ibutinib synthetic intermediates and final products, especially the content of isomer impurities, to ensure the quality of drugs and clinical drug safety provides a strong guarantee.
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(2022/03/02)

Preparation of
The invention relates to a preparation process of. Specific examples of compound formula I (5 - amino -3 - (4 - phenoxyphenyl) - 1H - pyrazole -4 - carbonitrile) and compound formula II ((S)-1 - (3 - hydroxypiperidine -1 - yl) prop -2 - (-1 - phenoxypheny
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Paragraph 0011; 0020-0021

(2021/11/03)

Preparation method of ibrutinib
The invention relates to a preparation method of ibrutinib and an intermediate thereof, belonging to the field of medicinal chemistry. According to the preparation method, the ibrutinib can be obtained through condensation, condensation, substitution, substitution and Suzuki reaction by taking a low-cost material flow as a starting material; and the method is low in cost, free of light delay reaction, high in yield, good in selectivity, short in route, few in generated three wastes and suitable for industrial large-scale production.
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Paragraph 0107-0111

(2021/08/06)

Purification method of ibrutinib crystal form A
The invention discloses a purification method of an ibrutinib crystal form A. According to the method, the purification of the ibrutinib crystal form A is realized by utilizing crystal form conversion. The method comprises the following steps: dissolving a crude product of the ibrutinib crystal form A, adding a seed crystal E to obtain an ibrutinib crystal form E, dissolving the crystal form E, and crystallizing to obtain the ibrutinib crystal form A with higher purity. The purification method of the ibrutinib crystal form A is simple in process and high in yield, and the purification problem that impurities in the ibrutinib crystal form A are difficult to remove is solved.
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Paragraph 0024-0026

(2021/08/07)

Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry
Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors. While typically α-substitutions inactivate acrylamides, we show that hetero α-substituted methacrylamides have higher thiol reactivity and undergo a conjugated addition-elimination reaction ultimately releasing the substituent. Their reactivity toward thiols is tunable and correlates with the pKa/pKb of the leaving group. In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide. This translated to comparable potency in protein labeling, in vitro kinase assays, and functional cellular assays, with improved selectivity. The conjugate addition-elimination reaction upon covalent binding to their target cysteine allows functionalizing α-substituted methacrylamides as turn-on probes. To demonstrate this, we prepared covalent ligand directed release (CoLDR) turn-on fluorescent probes for BTK, EGFR, and K-RasG12C. We further demonstrate a BTK CoLDR chemiluminescent probe that enabled a high-throughput screen for BTK inhibitors. Altogether we show that α-substituted methacrylamides represent a new and versatile addition to the toolbox of targeted covalent inhibitor design.
Reddi, Rambabu N.,Resnick, Efrat,Rogel, Adi,Rao, Boddu Venkateswara,Gabizon, Ronen,Goldenberg, Kim,Gurwicz, Neta,Zaidman, Daniel,Plotnikov, Alexander,Barr, Haim,Shulman, Ziv,London, Nir
supporting information
p. 4979 - 4992
(2021/05/04)

Preparation method of ibrutinib intermediate
The invention relates to a preparation method of ibrutinib and an intermediate thereof, belonging to the field of medicinal chemistry. According to the preparation method, ibrutinib can be obtained through condensation, cyclization, substitution, Suzuki reaction and acylation reaction by taking a low-cost material flow as a starting material. The method is low in cost, free of light delay reaction, high in yield, good in selectivity, short in route, few in generated three wastes and suitable for industrial large-scale production.
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(2021/08/06)

Continuous low-cost preparation method of ibrutinib
The invention discloses a continuous low-cost preparation method of ibrutinib, belonging to the technical field of medicine synthesis. The method comprises the following steps: 1) carrying out a Mitsunobu reaction on a raw material, DIAD and triphenylphosphine to obtain an intermediate; 2) removing a Boc protecting group from a reaction solution, extracting unreacted 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, and feeding and applying the unreacted 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine indiscriminately; 3) adding dichloromethane into a water phase obtained afterraw material extraction in the step 2), adjusting a pH value by using an aqueous sodium hydroxide solution, separating out an organic phase, carrying out drying by using anhydrous sodium sulfate, anddirectly adding triethylamine and acryloyl chloride for an acylation reaction; and 4) conducting washing, removing impurities, and performing evaporating to remove solvents to obtain ibrutinib. The preparation method of the invention overcomes the defects of large residual quantity of raw materials, excessive use of triphenylphosphine oxide, high cost and the like in the prior art, has the advantages of high comprehensive yield, low production cost, environment friendliness and continuity, and is suitable for industrial production.
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(2020/05/30)

PROCESSES AND INTERMEDIATES FOR PREPARING A BTK INHIBITOR
Disclosed is a process for the preparation of certain intermediates, e.g. process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof, in an enantioenriched form, which intermediate and processes are useful in the preparation of a BTK inhibitor, such as ibrutinib.
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(2020/12/07)

Synthetic method of high-purity ibrutinib
The invention relates to a synthetic method of high-purity ibrutinib, and belongs to the technical field of pharmaceutical chemicals. The synthetic method of ibrutinib comprises the following steps: firstly, reacting an acyl halide derivative III with an alkaline compound IV, and further reacting with a formula II to obtain high-purity ibrutinib. The synthetic method of ibrutinib can effectively reduce related substance impurities V, is simple and convenient to operate, mild in reaction and high in purity, and is convenient for industrial scale-up production.
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Paragraph 0033-0051

(2021/01/04)

Synthesis method of ibrutinib
The invention relates to the technical field of medicine synthesis, in particular to a synthesis method of ibrutinib. In the prior art, the purity and yield of synthesized ibrutinib are not high enough, the product quality is influenced by low purity, and raw material waste and high industrial production cost are caused by low yield. Based on the above problems, the invention provides a synthesismethod of ibrutinib. The method comprises the following steps of: preparing a high-purity intermediate M3, carrying out acylation reaction on the high-purity intermediate M3 and acryloyl chloride under alkaline conditions, and carrying out a series of purification steps to obtain high-purity and high-yield ibrutinib, thereby enhancing the product quality and greatly lowering the raw material wasteand industrial production cost.
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Paragraph 0028-0074

(2020/09/20)

Preparation method of pyrazolopyrimidine compound
The invention discloses a preparation method of a pyrazolopyrimidine compound. The preparation method of the pyrazolopyrimidine compound provided by the invention comprises the steps of: in an organicsolvent, under the action of alkali and water, carrying out amidation reaction on the compound shown as formula 1 and the compound shown as formula 2. Specifically, the alkali is selected from one ormore of potassium phosphate salt, sodium phosphate salt, sodium acetate, potassium acetate, sodium citrate and potassium citrate. The method has the advantages of easy operation, mild reaction conditions, good purity and high yield, and is more suitable for industrial production.
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Paragraph 0066-0068; 0073-0075

(2019/01/24)

Catalytic Azido-Hydrazination of Alkenes Enabled by Visible Light: Mechanistic Studies and Synthetic Applications
A visible-light-enabled catalytic intermolecular azido-hydrazination method for unactivated alkenes is developed via an orderly radical addition sequence. This transformation features metal-free and redox-neutral conditions and is applicable to a wide range of alkenes with commercially available reagents. Mechanistic and kinetic studies reveal that the efficient generation of azide radical enabled by fluorenone under visible-light is critical to this methodology. The β-azido alkyl hydrazines prepared with this reaction can be conveniently derived to valuable synthetic building blocks, and one of the products has been successfully applied in the total synthesis of (±)-ibrutinib, which is used to treat B cell cancers. (Figure presented.).
Wang, Peng,Luo, Yunxuan,Zhu, Songsong,Lu, Dengfu,Gong, Yuefa
p. 5565 - 5575
(2019/11/14)

Ibrutinib preparation method
The invention relates to the technical field of medicine processing, and discloses an ibrutinib preparation method, which comprises: sequentially preparing materials for preparing ibrutinib, wherein the materials comprise a 3-aminopiperidine compound, D-p
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Paragraph 0018; 0023; 0030; 0037

(2019/01/22)

Method for preparing ibrutinib
The invention discloses a method for preparing ibrutinib. The method includes the following steps of 1, preparation of IB-A, 2, preparation of IB-B, 3, preparation of IB-C, 4, preparation of IB-D, 5,preparation of IB-E, 6, preparation of IB-F, 7, preparation of IB-G, 8, preparation of IB-H, and 9, preparation of IB-J. The method has the advantages that the process is mature and stable, the quality of the product is stable, the production process is safe and reliable, and the ibrutinib is suitable for industrial production.
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(2018/03/26)

Method for preparing ibrutinib
The invention relates to a method for preparing ibrutinib. The method comprises the following steps: carrying out an acylation reaction between a compound A ((R)-3-(4-phenoxyphenyl)-1-(piperidine-3-yl)-1H-pyrazolo[3,4-D] pyrimidine-4-amine) and a compound C so as to obtain an intermediate B, and finally obtaining the ibrutinib through an elimination reaction. The preparation method provided by theinvention is mild in reaction conditions, less in impurity, high in yield, easy to enlarge and applicable to industrialized production.
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Paragraph 0041-0042; 0060; 0064

(2018/05/16)

PROCESS FOR PREPARING IBRUTINIB
The present application relates to a method for preparing Ibutinib as shown by the following synthetic route and the intermediate compounds involved therein.
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(2018/03/25)

A according to lu tini and its key intermediate for the preparation of the new method (by machine translation)
The invention relates to a according to lu tini and its key intermediate for the preparation of the new method, the existing synthetic process avoids the more stringent reaction conditions, and the expensive starting material and reagent. The oxide by a one-pot reaction synthesis of key intermediate, simplified post-processing operation is relatively complex, and the cost is reduced. The obtained intermediate purity of 99% or more, the yield is higher, the operation is simple, and is suitable for industrial production. (by machine translation)
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(2018/03/26)

A N - propylene carbonyl piperidine derivatives for the preparation of
The invention relates to a method for preparing an N-propylene carbonyl piperidine derivative, in particular to a new midbody for preparing ibrutinib, a preparation method of the new midbody and a method for preparing the ibrutinib, and belongs to the technical field of pharmacy. The method relates to a reaction as specified in the following formula (please see the specification for the formula). The method is easy to operate, capable of lowering cost and beneficial to industrial production.
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(2018/10/11)

A synthetic method for ibrutinib
A synthetic method for ibrutinib (I) is provided. Nano-magnetic material-loaded triphenylphosphine (PPh3@NMM) is adopted and subjected to a Mitsunobu reaction, efficient preparation of an intermediateIV and efficient separation of a by-product triphenylphosphine oxide are achieved, and an intermediate IV is further acrylated to obtain ibrutinib. The whole route has the advantages of simple operation, a low cost, a high yield, obvious reduction of three wastes, and the like, and the method is suitable for industrial scale-up production.
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Paragraph 0048

(2018/10/27)

Method for preparing and purifying ibrutinib
The invention discloses a method for preparing and purifying ibrutinib. (R)-3-(4-phenoxyphenyl)-1-(piperidine-3-yl)-1H-pyrazol [3,4-d] opyrimidine-4-amoina (II) and acryloyl chloride are condensed under the effect of mixing alkali containing organic alkali and a metal hydroxide to produce ibrutinib (I). The synthesizing method is simple in post-treatment operation, free from a large number of floccules, high in product purity and yield, and suitable for industrial production.
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Paragraph 0022; 0023; 0025

(2018/11/22)

Ibrutinib synthesis method
The invention provides an ibrutinib synthesis method and belongs to the field of medicine synthesis. The synthesis method includes the step that a compound M and a compound of formula I undergo acylation reaction in the presence of alkaline. The synthesis method is mild in reaction conditions, side reaction is less, obtained ibrutinib is high in yield, and the purity is 99.50 or above. A syntheticroute of the synthesis method is described as follows.
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Paragraph 0055; 0060; 0061; 0062

(2018/04/02)

Trisubstituted phosphinimine compound and preparation method and application thereof
The invention discloses a trisubstituted phosphinimine compound and a preparation method and application thereof. The trisubstituted phosphinimine compound adopts a general formula as shown in the specification, wherein R1, R2 and R3 are independently selected from C1-C10 alkyl, C1-C10 cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; and R4 is independently selected from hydrogen, an amino protecting group and an acryloyl group. The trisubstituted phosphine adopted in the trisubstituted phosphinimine compound can serve as an effective protecting group to be applied in the synthesis of Ibrutinib.
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(2017/08/25)

AN IMPROVED PROCESS FOR THE PREPARATION OF IBRUTINIB
The present invention relates to an improved process for the preparation of Ibrutinib with high purity and high yields. The present process is cost effective and feasible in large scale production also. The present process avoids the mitsunobu reagent conditions also. The present Invention also relates to a process for the preparation of Crystalline form A and Crystalline form C of Ibrutinib.
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Paragraph 14; 15

(2018/02/28)

PROCESS FOR THE PREPARATION OF IBRUTINIB
The present invention relates to a process for the preparation of 1-[(3R)-3 -[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl] -1-piperidinyl]-2-propen-1-one or Ibrutinib of Formula (I). The present invention further relates to a process for the preparation highly pure 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1 H-pyrazolo[3,4-d]pyrimidin-1-yl] -1-piperidinyl]-2-propen-l-one or Ibrutinib.
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(2017/12/28)

Refined preparing method of ibrutinib
The invention discloses a refined preparing method of ibrutinib. According to the method, a compound with a formula 1 is used as a raw material, and the compound with the formula 1 and a compound with a formula 2 are reacted in the presence of a mitsunobu reaction reagent to generate a compound with a formula 3, and a protecting group of the compound with the formula 3 is removed in the presence of acid to generate a compound with a formula 4; the compound with the formula 4 and a compound with a formula 5 are subjected to a Suzuki coupling reaction in the presence of alkali and a catalyst to generate a compound with a formula 6; the compound with the formula 6 and acryloyl chloride are reacted in the presence of alkali to generate ibrutinib. Finally column chromatography separation is conducted, macroporous adsorption resin is adopted as filler, the eluent is ethyl acetate or petroleum ether, and a high-purity material is obtained. According to the refined preparing method of ibrutinib, the yield is high in every step, the product is convenient to purify, the purity is high, and the industrialized production prospect is good.
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(2017/12/09)

Preparation method of Bruton's tyrosine kinase inhibitor
The invention relates to the field of drug synthesis, specifically to a preparation method of a Bruton's tyrosine kinase inhibitor. The new method comprises: carrying out a dark reaction between 4-amino-3-(4-phenoxylphenyl)-1H-pyridino(3,4-d)pyrimidine an
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Paragraph 0047; 0048

(2017/08/31)

Preparation method of antitumor medicine ibrutinib
The invention discloses a preparation method of an antitumor medicine ibrutinib, and belongs to the technical field of organic synthesizing. The specific synthesizing route is shown in the description. The preparation method has the advantages that the reaction conditions are moderate, the operation is simple, the cost is low, the purifying is convenient, the environment-friendly effect is realized, the optical purity of a product is high, and the preparation method is suitable for industrialized production.
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Paragraph 0050; 0051; 0052

(2017/10/22)

PROCESS FOR THE PREPARATION OF IBRUTINIB AND NEW SYNTHESIS INTERMEDIATE
Subject-matter of the invention is a process for the preparation of ibrutinib and intermediate compound.
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(2017/02/24)

PROCESS FOR THE SYNTHESIS OF STABLE AMORPHOUS IBRUTINIB
Disclosed herein is a new route of synthesis and a new stable amorphous form of ibrutinib. Also disclosed are pharmaceutical compositions, oral dosage forms and the use of the amorphous ibrutinib in the treatment of mantle cell lymphoma or chronic lymphocytic leukemia.
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Page/Page column 19

(2017/09/05)

According to lu tini synthesis method
The invention discloses a synthesis method of ibrutinib. The method uses Suzuki coupling reaction and Kumada coupling reaction, does not need to separate the intermediate, obtains the intermediate (9) at high yield by a one-pot process, and uses mixed anhydrides instead of acryloyl chloride. The technique utilizes cheap 4-halodianisole as the initial raw material, adopts Suzuki coupling reaction and Kumada coupling reaction, and uses the one-pot process. The whole route is disclosed in the specification. The method can obtain the intermediate (9) (the chemical purity and optical purity are greater than or equal to 99%) at high yield without separating and purifying the intermediate, and avoids microwave, high temperature/high pressure and other specific reaction conditions; and the acrylic acid and mixed anhydrides generated by acyl chloride and sulfonyl chloride are used instead of the acryloyl chloride in the last step to avoid the amidation reaction of the intermediate (10) in multiple sites and reduce the generation of the byproduct, thereby obtaining the high-purity ibrutinib at high yield. The method has the advantages of short process route and lower cost, and is beneficial to the environment and suitable for industrialized scale-up production.
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(2017/08/31)

PROCESS FOR PREPARING PURE LH-PYRAZOLO[3,4-D] PYRIMIDINE DERIVATIVE
The present invention relates to an efficient and industrially advantageous process for the preparation of pure lH-pyrazolo[3,4-d] pyrimidine derivative. In particular the present invention provides a process for the preparation of pure 4-amino-3-(4- phenoxyphenyl)-lH-pyrazolo[3,4-d] pyrimidine, a key intermediate of ibrutinib. Particularly, the present invention provides a process for the preparation of 3-amino-4-cyano-5-(4-phenoxy phenyl)pyrazole, wherein none of the intermediates have been isolated, an important precursor for the preparation of 4-amino-3-(4-phenoxyphenyl)- lH-pyrazolo[3,4-d] pyrimidine.
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(2017/10/13)

High-efficiency preparation method for ibrutinib
The invention discloses a high-efficiency preparation method for ibrutinib, which belongs to the technical field of organic synthesis. A concrete synthetic route is shown in a specification. The method has the advantages of mild reaction condition, simple operation, low cost, convenient purifying, friendly environment, and high product optical purity, and is suitable for industrial production.
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(2018/04/01)

PROCESS FOR PREPARING IBRUTINIB AND ITS INTERMEDIATES
The present invention provides efficient, economical, and improved methods for synthesizing ibrutinib and intermediates thereof. The invention involves a unique biphasic acylation reaction system which advantageously allows for easy separation of ibrutinib from the reaction mixture without additional extraction and wash steps. The isolated ibrutinib formed using the methods described herein can be useful in the preparation of an amorphous form of ibrutinib. In some embodiments, the isolated ibrutinib produced by the processes described herein is a homogenous solution of ibrutinib and DMSO which may be directly used in the formation of the amorphous polymorph. In some embodiments, the isolated ibrutinib is solid ibrutinib. The solid ibrutinib may also be used in the formation of amorphous ibrutinib.
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Paragraph 0127; 0128; 0133

(2017/06/23)

Novel crystal form of ibrutinib and preparation method of novel crystal form
The invention provides a novel crystal form of ibrutinib. The novel crystal form is named as a crystal form 1; the 2-theta value of the X-ray powder diffraction pattern of the novel crystal form has characteristic peaks at 5.8 degrees +/- 0.2 degree, 10.8
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Paragraph 0120; 0121

(2017/10/31)

PROCESS FOR THE PREPARATION OF 1-[(3R)-3-[4-AMINO-3-(4-PHENOXYPHENVL)-1H- PVRAZOLO[3,4-D]PYRINIIDIN-1-Y1]-1-PIPERIDINVL]-2-PROPEN-1-ONE AND ITS POLYMORPHS THEREOF
The present invention relates to an improved process for the preparation of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)- 1 H-pyrazolo[3,4-d]pyrimidin- 1 -yl]- 1 -piperidin yl]-2-propen-1-one compound of formula- 1 and its polymorphs thereof, which is represented by the following structural formula:
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Page/Page column 36

(2016/11/14)

Preparation method of ibrutinib
The invention relates to the technical field of medicine, in particular to a preparation method of ibrutinib. The preparation method of ibrutinib comprises the following steps that 4-amino-3-(4-phenoxy phenyl)-1H-pyrazol[3,4-d]pyrimidine and S-1-tert-butyloxycarbonyl-3-hydroxyl piperidine are prepared into a compound shown in the formula IV (please see the formula in the description) through a Mitsunobu reaction, and a Boc protecting group of the compound shown in the formula IV is removed to prepare a compound shown in the formula V (please see the formula in the description); the compound shown in the formula V and acrylic ester are prepared into a compound shown in the formula I (please see the formula in the description) in the presence of a catalyst and an activating agent. According to the preparation method, the reaction process is mild in condition, few reaction steps are needed, high temperature and copious cooling are not needed, no high-toxicity reagent is adopted, and the whole synthesizing process is stable and controllable; ibrutinib prepared through the method is high in yield and quality and has the advantages of being good in stability, high in purity, convenient to store and the like.
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Paragraph 0039; 0069-0077

(2017/10/20)

PREPARATION OF PURE AMORPHOUS IBRUTINIB
The present invention refers to the preparation of the amorphous form of the Bruton's tyrosine kinase (Btk) inhibitor l -((R)-3-(4-armno-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1- yl)piperidin-1-yl)prop-2-en-1-one (ibrutinib). In particular, the i
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(2017/01/31)

A PROCESS FOR THE PREPARATION OF IBRUTINIB
The present invention provides a process for the preparation of ibrutinib of Formula I.
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Page/Page column 15-16

(2016/10/11)

PROCESS FOR THE PREPARATION OF IBRUTINIB
A processes for the preparation of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4- d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one (ibrutinib). The disclosed process may be useful for preparing ibrutinib that may be included in pharmaceutical dosage forms.
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(2017/01/02)

Ibrutinib preparation method, ibrutinib intermediate, and ibrutinib intermediate preparation method
The present invention provides an ibrutinib preparation method, which comprises that (a) a compound (3) reacts with diethyl sulfate to obtain a compound (4); (b) the compound (4) reacts with a hydrazine dihydrochloride to obtain a compound (5); (c) the compound (5) reacts with formamide to obtain a compound (6); (d) after the compound (6) reacts with (R)-1-Boc-3-hydroxypiperidine, an acid is added to make a compound (7) be subjected to a deprotection reaction to obtain a compound (8); and (e) the compound (8) reacts with acryloyl chloride to obtain a compound (9) ibrutinib. The present invention further provides an ibrutinib intermediate represented by a formula (4) and a preparation method of the intermediate compound (8). According to the present invention, the method has advantages of low cost, good safety and high yield, and is suitable for large-scale production. The reaction route is defined in the specification.
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(2017/04/14)

SYNTHESIS OF A BRUTON'S TYROSINE KINASE INHIBITOR
Described herein is the synthesis of Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3 -(4-phenoxyphenyl)- 1H-pyrazolo [3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.
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Paragraph 00202-00211

(2016/11/07)

Preparation method for ibrutinib
The invention discloses a preparation method for ibrutinib and belongs to the technical field of drug synthesis. The preparation method specifically includes the steps that 3-amino-4-cyano pyrazol and formamidine acetate serve as initial raw materials, and ibrutinib is obtained through a cyclization reaction, a halogenating reaction, a nucleophilic substitution reaction, a Mitsunobu reaction and an amidation reaction. According to the method, the raw materials are easy to obtain, conditions are mild, the process operability and controllability are high, cost is low, the yield is high, fewer side products are generated, purification is easy, and the high-quality product is obtained.
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(2016/10/10)

Method for synthesizing ibrutinib
The invention provides a method for synthesizing ibrutinib. The method takes 4,6-dihydroxypyrimidine as an initial raw material, the material is subjected to formylation and chlorination to obtain a compound in a formula 3; the compound in the formula 3 and a compound in a formula 4 are subjected to a reaction to obtain a compound in a formula 5; the compound in the formula 5 is subjected to oxidation to obtain a compound in a formula 6; the compound in the formula 6 is subjected to ammonification to obtain a compound in a formula 7; the compound in the formula 7 and hydrazine hydrate are subjected to a reaction for closing pyrazole ring to obtain a compound in a formula 8; the compound in the formula 8 and a compound in a formula 9 are subjected to an alkylation reaction to obtain a compound in a formula 10; the compound in the formula 10 is subjected to acid deprotection to obtain a compound in a formula 11; and the compound in the formula 11 and acryloyl chloride are subjected to the reaction to obtain ibrutinib. The invention also discloses an ibrutinib intermediate. The raw materials have the advantages of low cost and easy acquisition, no dangerous highly-toxic product, mild reaction condition, no requirement of cryogenic cooling and high temperature, and simple operation, and is suitable for industrial production.
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(2016/10/09)

A PROCESS FOR THE PREPARATION OF IBRUTINIB
The present invention provides processes for the preparation of ibrutinib, intermediate compounds of Formula VI and Formula VIII, and salts thereof. The processes of the present invention are commercially viable, cost-effective, environmentally friendly, and make use of inexpensive, non-hazardous, safe chemicals that are easy to handle.
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(2016/06/15)

Preparation method of Ibrutinib drug impurity
The invention belongs to the field of pharmaceutical synthesis, and relates to an impurity in the bulk pharmaceutical chemical production process and a preparation method of the impurity, in particular to a process impurity of Ibrutinib 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1Hpyrazole [3,4-d]pyrimidine-1-yl]-1-piperidyl]-2-propylene-1-ketone and a preparation method of the process impurity.
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(2017/10/03)

SOLID STATE FORMS OF IBRUTINIB
The present invention encompasses solid state forms of Ibrutinib, including forms G, J and K, and pharmaceutical compositions thereof.
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Paragraph 0056

(2016/02/29)

Method for Preparing Ibrutinib
Provided is a method for preparing Ibrutibin (I), and steps of preparing same comprise: 4-benzyloxybenzoyl chloride (II) is used as a raw material, condensation and methoxidation reactions occur among 4-benzyloxybenzoyl chloride (II), malononitrile, and dimethyl sulfate to generate 4-benzyloxyphenyl(methoxy)vinylidenedicyanomethane (III), pyrazole cyclization occurs between the intermediate (III) and 1-(3R-hydrazino-1-piperidino)-2-propylene-1-ketone (IV) to acquire 1-[(3R)-[3-(4-benzyloxyphenyl)-4-nitrile-5 -amino-1H-pyrazole]-1-piperidino]-2 propylene-1-ketone (V), and pyrimidine cyclization occurs between an intermediate (V) and a cyclizing agent to prepare Ibrutinib (I). In the preparation method, the raw material is readily available, and the process is simple, economical, environmentally friendly, and is suitable for industrial production.
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(2016/10/04)

Preparation method of ibrutinib
The invention belongs to the field of drug synthesis and relates to preparation of a crude drug and an intermediate, in particular to a preparation method of ibrutinib 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one. The method is characterized in that (1) 3-(4-Phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (SM1) and (S)-1-Boc-3-hydroxypiperidine (SM2) are adopted as starting materials and subjected to a Mitsunobu reaction, and an intermediate (-1): (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is obtained and condensed with acrylic anhydride for an amidation reaction, and the finished product ibrutinib is prepared through recrystallization.
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Paragraph 0078; 0079

(2017/01/02)

Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: A comparative study
Ibrutinib is a covalent and irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has been approved for the treatment of haematological malignancies, such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstr?m's macroglobulinemia. The covalent and irreversible nature of its molecular mode of action allows identification and monitoring of its target in an activity-based protein profiling (ABPP) setting. Fluorescent and biotinylated ibrutinib derivatives have appeared in the literature in recent years to monitor BTK in vitro and in situ. The work described here complements this existing methodology and pertains a comparative study on the efficacy of direct and two-step bioorthogonal ABPP of BTK.
Liu, Nora,Hoogendoorn, Sascha,Van De Kar, Bas,Kaptein, Allard,Barf, Tjeerd,Driessen, Christoph,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Van Der Stelt, Mario,Overkleeft, Herman S.
p. 5147 - 5157
(2015/05/13)

Chemical Properties

Boiling Point: 715.0±60.0 °C at 760 mmHg
Flash Point:386.2±32.9 °C
Density: 1.3±0.1 g/cm³
Solubility:Soluble in DMSO ( up to at least 25 mg/ml)
Storage Temp.:-20°C
PKA: 4.09±0.30(Predicted)
PSA: 99.16000
LogP: 4.73640

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Chemical Properties

Boiling Point: 715.0±60.0 °C at 760 mmHg

Flash Point:386.2±32.9 °C

Density: 1.3±0.1 g/cm³

Solubility:Soluble in DMSO ( up to at least 25 mg/ml)

Storage Temp.:-20°C

PKA: 4.09±0.30(Predicted)

PSA: 99.16000

LogP: 4.73640

Global suppliers and manufacturers of 936563-96-1total 242 suppliers on LookChem

Article Database

936563-96-1

Articles about 936563-96-1Total 55 be found

More Articles about upstream products of 936563-96-1

Chemical Properties

Boiling Point: 715.0±60.0 °C at 760 mmHg

Flash Point:386.2±32.9 °C

Density: 1.3±0.1 g/cm3

Solubility:Soluble in DMSO ( up to at least 25 mg/ml)

Storage Temp.:-20°C

PKA: 4.09±0.30(Predicted)

PSA: 99.16000

LogP: 4.73640

Global suppliers and manufacturers of 936563-96-1total 242 suppliers on LookChem

Density: 1.3±0.1 g/cm³