METHOD OF PRODUCING METHYL{4,6-DIAMINO-2-[5-FLUORO-1-(2-FLUOROBENZYL)-1H-PYRAZOLO[3,4-b]PYRIDIN-3-YL]PYRIMIDIN-5-YL}CARBAMATE Russian patent published in 2025 - IPC C07D471/04 C07D295/04 

Abstract RU 2841069 C1

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate of formula (I) in crystalline form of modification I, where the X-ray diffraction pattern of said compound in modification I shows maximums of peak of angle 2-theta at 5.9, 6.9, 22.7. According to the disclosed method, a hydrochloride of a compound of formula (I) is obtained by heating the compound of formula (IX) in tetrahydrofuran as a solvent, adding 1.0 to 1.2 eq. of methyl chloroformate, stirring for a reaction time of 1 to 10 hours and isolating the hydrochloride of the compound of formula (I). Di-DMSO solvate of the compound of formula (I) is then obtained by dissolving the hydrochloride of the compound of formula (I) in DMSO, adding tri-n-butylamine and activated carbon, removing the activated carbon, crystallising the di-DMSO solvate by cooling and adding ethyl acetate, separating the di-DMSO solvate in crystalline form and washing with a mixture of DMSO and ethyl acetate. Compound of formula (I) is then obtained in the crystalline form of modification I, where 1.1) di-DMSO solvate of the compound of formula (I) is dissolved in DMSO and ethanol is added at the ratio of DMSO to ethanol from 2:1 to 6:1 wt./wt.; 1.2) the dissolved compound of formula (I) is then crystallized from the solution by adding water; 1.3) formed suspension is then cooled to temperature from 5 °C to 50 °C and 1.4) the formed crystals in step 1.2 are then agglomerated to obtain a product of the active compound by adding isopropyl acetate, where ratio of weight of isopropyl acetate and sum of weight of compound of formula (I) plus weight of ethanol ranges from 0.3 to 2.0. Invention also relates to a version of the method of producing a compound of formula (I) and a method of producing the hydrochloride of the compound of formula (I).

EFFECT: method enables to obtain the desired compound with high output, high degree of purity and improved physical characteristics.

9 cl, 2 dwg, 17 ex

Similar patents RU2841069C1

Title Year Author Number
PRODUCT OF ACTIVE COMPOUND OF METHYL{4,6-DIAMINO-2-[5-FLUORO-1-(2-FLUOROBENZYL)-1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL]PYRIMIDIN-5-YL}CARBAMATE, HAVING IMPROVED PROPERTIES, PREPARATION AND COMPOSITION THEREOF 2019
  • Fey, Peter
  • Sowa, Michal
  • Brockob, Joerg
  • Longerich, Markus
  • Becker, Guido
  • Neumann, Heike
RU2818488C2
METHOD OF PRODUCING (4S)-4-(4-CYANO-2-METHOXYPHENYL)-5-ETHOXY-2,8-DIMETHYL-1-4-DIHYDRO-1,6-NAPHTHYRIDINE-3-CARBOXAMIDE AND ITS PURIFICATION FOR USE AS PHARMACEUTICAL ACTIVE INGREDIENT 2015
  • Plattsek Iogannes
  • Garke Gunnar
  • Grunenberg Alfons
RU2729998C2
POLYMORPHOUS FORMS OF 1-[4-(5-CYANOINDOLE-3-YL)BUTYL]-4-(2-CARBAMOYLBENOFURAN-5-YL)-PIPERAZINE HYDROCHLORIDE 2002
  • Bate Andreas
  • Khel'Fert Bernd
  • Nojenfel'D Shteffen
  • Knil' Khajke
  • Bartel'S Mattias
  • Rudol'F Zuzanne
  • Bettkher Khenning
RU2303598C2
OBTAINING INTERMEDIATE PRODUCTS FOR SYNTHESIS OF POSACONAZOLE 2011
  • De-Suza Dominik
  • Joshi Shrirang V.
  • Bkhuta Zachin
  • Pajz Abkhinaj S.
  • Chavan Dattatraja N.
  • Metkar Shashikant D.
RU2580318C2
PYRIDO[1,2-A]PYRIMIDONE ANALOG, ITS CRYSTAL FORM, ITS INTERMEDIATE COMPOUND AND METHOD FOR THEIR PREPARATION 2016
  • Yu, Tao
  • Li, Ning
  • Kong, Lingwei
  • Jiang, Peipei
  • Wang, Yong
  • Rong, Zhemin
  • Wang, Changjun
  • Guo, Feng
  • Li, Zongbin
  • Wang, Zheng
  • Wu, Jiahu
  • Wu, Chengde
RU2753696C2
METHOD OF PRODUCING TWO 4-{[(2S)-2-{4-[5-CHLORO-2-(1H-1,2,3-TRIAZOL-1-YL)PHENYL]-5-METHOXY-2-OXOPYRIDIN-1(2H)-IL} BUTANOYL]AMINO}-2-FLUOROBENZAMIDE DERIVATIVES 2019
  • Egger, Julian
  • Goetz, Daniel
  • Sowa, Michal
RU2804663C2
METHOD OF OBTAINING TAPINAROF 2018
  • Andrews Ian Paul
  • Calandra Nicholas
  • Davis Tyler Andrew
  • Sudini Ravinder Reddy
RU2795144C2
2-(AZAINDOL-2-YL)BENZIMIDAZOLE DERIVATIVES AS PAD4 INHIBITORS 2012
  • Atkinson Stephen John
  • Barker Michael David
  • Campbell Matthew
  • Diallo Hawa
  • Douault Clement
  • Garton Neil Stuart
  • Liddle John
  • Sheppard Robert John
  • Walker Ann Louise
  • Wellaway Christopher
  • Wilson David Matthew
RU2611010C2
N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(2-METHYLPROPYLOXY)PHENYLMETHYL) CARBAMIDE SALTS AND PREPARATION OF SAID SALTS 2005
  • Tjugesen Mikkel'
  • Shlinger Natali
  • Tol'F Bo-Ragnar
  • Blatter Fritts
  • Bergkhauzen Jorg
RU2387643C2
SUBSTITUTED DERIVATIVES OF N-[2-(4-PHENOXYPIPERIDINE-1-YL)-2-(1,3-THIAZOLE-5-YL)ETHYL]BENZAMIDE AND N-[2-(4-BENZYLOXYPIPERIDINE-1-YL)-2-(1,3-THIAZOLE-5-YL)ETHYL]BENZAMIDE AS P2X7 RECEPTOR ANTAGONISTS 2017
  • Pevarello Paolo
  • Prandi Adolfo
RU2755705C2

RU 2 841 069 C1

Authors

Fey, Peter

Bremeyer, Nadine

Longerich, Markus

Frenzel, Thomas

Faber, Helene

Sowa, Michal

Brockob, Joerg

Becker, Guido

Neumann, Heike

Dates

2025-06-02Published

2021-06-15Filed