Crystalline μ modification of 1 - [(3R) -3- [4-amino-3- (4-phenoxyphenyl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl] -1-piperidyl] - 2-propenyl-1-one, method for its preparation and pharmaceutical composition based on it
Михайлов Олег Ростиславович (RU),Уваров Николай Александрович (RU),Малин Александр Александрович (RU)
申请号：
RU2018120909
公开号：
RU2018120909A
申请日:
2018.06.06
申请国别(地区):
RU
年份:
2019
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry and a novel crystalline modification of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidyl]-2-propenyl-1-one (Ibrutinib - international non-proprietary name). Crystalline Ibrutinib μ-modification is characterized by the following set of interplanar distances (d, Å) and corresponding intensities (I, %): 15.477 Å - 42.64 %； 11.171 Å - 19.92 %； 9.896 Å - 17.53 %； 8.207 Å - 35.06 %； 7.137 Å - 28.61 %； 6.716 Å - 27.49 %； 6.433 Å - 39.13 %； 6.200 Å - 36.19 %； 5.849 Å - 35.62 %； 5.641 Å - 43.20 %； 5.516 Å - 43.90 %； 5.268 Å - 46.14 %； 5.053 Å - 49.65%； 4.845 Å - 59.61%； 4.667 Å - 70.13%； 4.581 Å - 63.67 %； 4.454 Å - 69.57 %； 4.316 Å - 59.61 %； 4.267 Å - 57.22 %； 4.152 Å - 100.00 %； 4.084 Å - 73.07 %； 3.955 Å - 53.16 %； 3.920 Å - 50.91 %； 3.863 Å - 47.41 %； 3.776 Å - 52.59 %； 3.732 Å - 39.69 %； 3.627 Å - 35.62 %； 3.578 Å - 39.13 %； 3.536 Å - 34.50 %； 3.476 Å - 35.62 %； 3.350 Å - 43.20 %； 3.259 Å - 31.00 %； 3.137 Å - 29.87 %； 3.082 Å - 32.12 %； 2.983 Å - 25.67 %； 2.937 Å - 25.11 %； 2.825 Å - 22.16 %； 2.768 Å - 19.35 %； 2.708 Å - 20.48 %； 2.610 Å - 16.97 %； 2.571 Å - 15.85 %； 2.482 Å - 16.41 %； 2.387 Å - 17.53 %； 2.379 Å - 16.97 %； 2.295 Å - 17.53 %； 2.240 Å - 14.59 %； 2.162 Å - 14.59 %. Method of producing crystalline μ-modification of Ibrutinib is performed by mixing the solution of Ibrutinib in an organic solvent at 25–80 °C with water in ratio of 1:2–1:4. Then it is frozen at cooling rate not lower than 60 deg/min, sublimated drying and additionally annealed at (90–110) °C during (0.5–5.0) hours. Invention also relates to a method of producing crystalline μ-modification of Ibrutinib, carried out by reacting (3R)-4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine with acryloyl chloride, wherein at the product crystallisation step a small amount of seed is introduced μmodification of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidyl]-
