Method for resolving racemic crizotinib

A technology of crizotinib and crizotinib, applied in the field of splitting racemic crizotinib, which can solve the problems of not being able to obtain optically pure single enantiomer, wide metastable zone width, and difficulty in nucleation , to achieve good selective adsorption performance, mild conditions and simple operation

Active Publication Date: 2021-03-26
SHANGHAI UNIV OF ENG SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the low solubility of (RS)-crizotinib, wide metastable zone width, and difficulty in nucleation, conventional crystallization resolution methods cannot obtain optically pure single enantiomers.

Method used

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  • Method for resolving racemic crizotinib
  • Method for resolving racemic crizotinib
  • Method for resolving racemic crizotinib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] A kind of preparation method of adsorbent, concrete steps are as follows:

[0060] (1) Preparation of MIL-53-NH 2 Nanocrystals: 0.76g AlCl 3 ·6H 2 O was dissolved in 15mL DMF, sonicated for 30min to obtain solution A, and then 0.56g NH 2 -H 2 Dissolve BDC in 15mL DMF, sonicate for 30min to obtain solution B, then add solution A dropwise to solution B at a rate of 1mL / min to obtain a mixed solution, transfer the mixed solution to a 100mL polytetrafluoroethylene reaction In the still, react at 150°C for 24h, and then centrifuge to remove the liquid component at 8500rpm for 8min, activate the obtained solid substance in DMF for 24h, wash with methanol for 3 times, and then remove the liquid component at 120°C After drying for 12 hours, the yellow powder MIL-53-NH was finally obtained 2 Nano crystals; wherein the amount of DMF added during activation meets the 4cm of the solid material interface;

[0061] (2) Dissolve 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydroc...

Embodiment 2

[0065] A kind of preparation method of adsorbent, concrete steps are as follows:

[0066] (1) Preparation of MIL-53-NH 2 Nanocrystals: 0.25g AlCl 3 ·6H 2 O was dissolved in 10mL DMF, sonicated for 25min to obtain solution A, and then 0.19g NH 2 -H 2 Dissolve BDC in 15mL DMF, sonicate for 25min to obtain solution B, then add solution A to solution B dropwise at a rate of 1mL / min to obtain a mixed solution, transfer the mixed solution to a polytetrafluoroethylene with a volume of 100mL Lined reaction kettle, reacted at 150°C for 24h, then centrifuged to remove the liquid component at 8500rpm, centrifuged for 8min, activated the obtained solid substance in DMF for 24h, washed 4 times with methanol, and then placed in Dry at 120°C for 15 hours to finally obtain MIL-53-NH in the form of yellow powder 2 Nano crystals; wherein the amount of DMF added during activation meets the 2cm of the solid material interface;

[0067] (2) Dissolve 1-ethyl-(3-dimethylaminopropyl)carbodiimid...

Embodiment 3

[0071] A kind of preparation method of adsorbent, concrete steps are as follows:

[0072] (1) Preparation of MIL-53-NH 2 Nanocrystals: 0.5g AlCl 3 ·6H 2 O was dissolved in 10mL DMF, sonicated for 26min to obtain solution A, and then 0.25g NH 2 -H 2Dissolve BDC in 15mL DMF, sonicate for 26min to obtain solution B, then add solution A to solution B dropwise at a rate of 1mL / min to obtain a mixed solution, transfer the mixed solution to a polytetrafluoroethylene with a volume of 100mL Lined reaction kettle, reacted at 150°C for 28h, then centrifuged to remove the liquid component at 8500rpm, centrifuged for 8min, activated the obtained solid substance in DMF for 24h, washed 5 times with methanol, and then Dry at 120°C for 18 hours to finally obtain MIL-53-NH in the form of yellow powder 2 Nano crystals; wherein the amount of DMF added during activation meets the 2cm of the solid material interface;

[0073] (2) Dissolve 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochlor...

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Abstract

The invention relates to a method for resolving racemic crizotinib, wherein the preparation method of an adsorbent comprises the steps: dissolving EDC, NHSS and (L)-Cit in an MES buffer solution, adding MIL-53-NH2 nanocrystals into the MES buffer solution, stirring, centrifuging, washing with deionized water, and carrying out vacuum drying. The adsorbent is applied to resolution of racemic crizotinib, and the method comprises the steps: firstly, soaking the adsorbent into a racemic crizotinib ethanol solution, stirring, carrying out centrifugal treatment, and collecting a supernatant and the adsorbent; adding the adsorbent into the collected supernatant again for centrifugal treatment, and then respectively collecting the supernatant and the adsorbent; and repeating the steps until the excess value of the crizotinib enantiomer in the supernatant is greater than the ee value at the lowest eutectic point, and then carrying out preferential crystallization to obtain (S)-crizotinib with the ee value of greater than 99% and (R)-crizotinib with the ee value of greater than 99%. The method disclosed by the invention is simple and feasible, the method for resolving racemic crizotinib by the adsorbent can obtain two pure enantiomers at the same time, and the separation effect is remarkable.

Description

technical field [0001] The invention belongs to the technical field of crizotinib, and relates to a method for splitting racemic crizotinib. Background technique [0002] Metal-organic framework materials are a class of crystalline materials obtained by self-assembly of metal ions or metal clusters and organic ligands. MOFs have the advantages of large specific surface area, clear pore size, and diverse chemical functions. They are used in catalysis, gas storage, and chemical sensing. And drug delivery and other fields have broad application prospects. Considering the importance of chirality, chiral research has now expanded to many fields, one of the most active fields is the design and synthesis of chiral MOFs, and exploring their applications in various fruitful research fields, including asymmetric catalysis, molecular Recognition, nonlinear optics and enantioselective separations. [0003] Homochiral metal-organic frameworks (h)-MOFs have attracted extensive attention...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J20/22B01J20/28B01J20/30C07D401/14
CPCB01J20/22B01J20/226B01J20/28004C07D401/14C07B2200/07
Inventor 陆杰王东博付宇佳张蕾蕾张江浩曹娇娇樊凡凡
Owner SHANGHAI UNIV OF ENG SCI
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