164 results about "Ibrutinib" patented technology

The invention discloses an ibrutinib purification method. The ibrutinib purification method comprises the following steps: 1) dissolving a crude product of ibrutinib in a moderately polar organic solvent, adding silica gel used for column chromatography, mixing the materials, carrying out stirring and filtering and concentrating obtained filtrate until dryness, thus obtaining a semi-finished product of ibrutinib; carrying out impurity separation with a simple silica gel adsorption method and obtaining the semi-finished product of ibrutinib with purity of 99.5% after purification; 2) then carrying out separation by recrystallization, thus obtaining a finished product of ibrutinib with purity over 99.8%. The ibrutinib purification method can achieve the effect of effectively removing the impurities in the crude product of ibrutinib, is simple in purification operation and high in yield and can be applied to industrial production.

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.

Crystalline Form I of ibrutinib, processes for its preparation, pharmaceutical compositions comprising the new Form, and use of Form I of ibrutinib for treating or delaying diseases or disorders related to activity of Bruton's tyrosine kinase (BTK) proteins are disclosed. The novel Form was characterized by X-ray powder diffraction, differential scanning calorimetry, and other techniques. It can be readily prepared and is suitable for use in the preparation of solid dosage forms.

Described herein are methods for treating and preventing graft versus host disease using ACK inhibitors. The methods include administering to an individual in need thereof an ACK inhibitor such as ibrutinib for treating and preventing graft versus host disease.

Disclosed is a process for the preparation of the following compounds:where R1, R1a and R2a have the definitions in the description, as well as a process to prepare other intermediates that may be useful to synthesize downstream products, especially compounds that are useful as medicaments, for instance Bruton's tyrosine kinase (Btk) inhibitors such as ibrutinib. Also disclosed are other processes, other intermediates and compounds per se.

The invention discloses a method for preparing ibrutinib amorpphis. The method comprises the following steps: (1) adding ibrutinib into a high-quality organic solvent, and heating to completely dissolve the ibrutinib; (2) adding the solution into an anti-solvent, and performing stirring and curing, wherein in the adding process, the temperature of the anti-solvent system is maintained below 5 DEG C; (3) filtering, decompressing and drying solids to obtain the ibrutinib amorpphis. The ibrutinib amorpphis prepared by the method is stable and suitable for preparation production.

The invention relates to a preparation method of ibrutinib. The preparation method comprises the following steps: allowing 4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo [3, 4-d] pyrimidine, 1-[3(S)-hydroxy-1-piperidinyl]-2-propen-1-one, and triphenylphosphine to be dissolved in tetrahydrofuran as a reaction solvent at a temperature of -20 to 100 DEG C, and then slowly adding diisopropyl azodicarboxylate, and stirring until the reaction is finished to obtain the ibrutinib. The preparation method provided by the invention has the advantages of easy availability of raw materials, mild conditions, simple process, economy and environmental protection, and is suitable for industrial production.

The invention discloses ibrutinib salts, crystals, a preparation method, pharmaceutical compositions and the application thereof. The crystals of the ibrutinib salts have a structure as shown in formula (I), wherein X is HCl, HBr or benzoic acid. The preparation method comprises the following steps: mixing ibrutinib with X in an organic solvent, heating to 40-130 DEG C, completely dissolving, cooling, and crystallizing. The crystals of the three ibrutinib salts are all of new crystal forms, have excellent solubility and thermal stability, greatly improve the hygroscopic property, and greatly improve the solubility and bioavailability of ibrutinib. The preparation method of the crystals is simple, is suitable for large-scale industrial production, and has a good industrial application prospect.

Crystalline Form I of ibrutinib, processes for its preparation, pharmaceutical compositions comprising the new Form, and use of Form I of ibrutinib for treating or delaying diseases or disorders related to activity of Bruton's tyrosine kinase (BTK) proteins are disclosed. The novel Form was characterized by X-ray powder diffraction, differential scanning calorimetry, and other techniques. It can be readily prepared and is suitable for use in the preparation of solid dosage forms.