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Surfactant systems for crystallization of organic compounds

A technology of organic compounds and surfactants, applied in the direction of purification/separation/stabilization of organic compounds, organic chemistry, organic chemical methods, etc., can solve problems such as changing the properties and limitations of crystals or aggregates

Pending Publication Date: 2019-05-03
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the possibility to modify the properties of crystals or aggregates is often limited by the technologies available for their production

Method used

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  • Surfactant systems for crystallization of organic compounds

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0032] Example 1: General protocol for crystallization of Compound 1

[0033] 500 mg of (N-(4-(chlorodifluoromethoxy)phenyl)-6-((R)-3-hydroxypyrrolidin-1-yl)-5 obtained from liquid-solid chromatography (LSC) -(1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide) was dissolved in MeOH (16v) at 60°C with mechanical stirring to give a clear solution. Antisolvent (8v) was added and after 20 min of stirring, a cooling ramp to room temperature (ca. 22° C.) was initiated by closing the oil bath (ca. 500 mL). Reslurry was carried out at 40°C for 24 hours in anti-solvent (8v). The resulting crystals were vacuum filtered on a frit (Por. 4).

[0034]

[0035] The conventional protocol used to crystallize Compound 1 resulted in very long filtration times and poor distribution control.

example 2

[0036] Example 2: Crystallization of Compound 1 with TPGS-750-M

[0037] Starting material (compound 1): columnar particles with a length of about 1 μm to 15 μm. The surface is generally smooth, with mostly regular edges. Particles are usually aggregated longitudinally. Most particles are smaller than 8 μm. XRPD: Type A

[0038] At 23°C, 500 mg of compound 1 was added to a solution of TPGS-750-M in water (2% wt) (16v). The resulting suspension was warmed to 40°C and stirred for 24 hours. The mixture was cooled to 23°C, stirred, and the suspension was filtered under vacuum (Por. 4).

[0039] Material obtained: aggregates / agglomerates (up to 300 μm) of columnar particles with a length of about 1 μm to 10 μm. The surface is smooth and rough, with irregular edges. Most particles are smaller than 6 μm. XRPD: Form A. Filtration time on laboratory scale: >5min

example 3

[0040] Example 3: Crystallization of Compound 1 with TPGS-750-M and 10% wtMeOH

[0041] 500mg of compound 1 was added to a solution of TPGS-750-M in water (2%wt) (16v) and MeOH (10%wt) at 23°C. The resulting suspension was warmed to 40°C and stirred for 24 hours. The mixture was cooled to 23°C, stirred, and the suspension was filtered under vacuum (Por. 4).

[0042] Resulting material: columnar particles with a length of about 1 μm to 20 μm. Most particles are smaller than 5 μm. No aggregates. XRPD: Form A. Filtration time on laboratory scale: >10min

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Abstract

The present invention is directed to methods for producing crystals or aggregates of organic compounds using a composition comprising a surfactant-water mixture, the organic compound and optionally anorganic solvent as starting composition. This surfactant system enables the production of a high variety of different crystals and aggregates. The method is in particular suitable for obtaining crystals and aggregates optimized for isolation and purification during chemical synthesis processes.

Description

technical field [0001] The present invention relates to methods for crystallizing or aggregating organic compounds. Organic compounds are crystallized or aggregated using compositions comprising a surfactant-water mixture. This method is particularly useful in the synthesis and purification of said organic compounds. Background technique [0002] Precipitation / crystallization of organic compounds from solution is a common and well-known means for the isolation and purification of said organic compounds, eg during chemical synthesis, for their purification. However, in many cases, the crystals or aggregates obtained are not conducive to processing, lead to long filtration times or handling problems, or exhibit suboptimal formulation properties, such as, for example, wettability. Therefore, modifying the form and size of crystals and aggregates of organic compounds is a tool for optimizing and especially accelerating the production of organic compounds. However, the possibi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14
CPCC07D401/14C07B63/04C07B2200/13C07D405/14
Inventor F·加卢M·帕尔芒捷
Owner NOVARTIS AG