New crystalline forms of n-[2-[[(2,3-difluoropheny)methyl) thio]-6{[(1r,2s)-2,3-dihydroxy-1-methylpropyl]oxy} 4-pyrimidinyl]-1-azetidinesulfonamide

A technology of -6-{, difluorophenyl, applied to medical preparations containing active ingredients, diseases of the digestive system, respiratory system, etc., can solve problems such as specific crystal form information of undisclosed compounds

Inactive Publication Date: 2013-05-08
ASTRAZENECA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] WO2006 / 024823 discloses the preparation of compound I, but does not disclose any specific information about the crystal form of the compound

Method used

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  • New crystalline forms of n-[2-[[(2,3-difluoropheny)methyl) thio]-6{[(1r,2s)-2,3-dihydroxy-1-methylpropyl]oxy} 4-pyrimidinyl]-1-azetidinesulfonamide
  • New crystalline forms of n-[2-[[(2,3-difluoropheny)methyl) thio]-6{[(1r,2s)-2,3-dihydroxy-1-methylpropyl]oxy} 4-pyrimidinyl]-1-azetidinesulfonamide
  • New crystalline forms of n-[2-[[(2,3-difluoropheny)methyl) thio]-6{[(1r,2s)-2,3-dihydroxy-1-methylpropyl]oxy} 4-pyrimidinyl]-1-azetidinesulfonamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0184] Example 1: Form A - Compound I Anhydrate

[0185] Compound I, N-[2-[[(2,3-difluorophenyl)methyl]sulfanyl]-6-{[(1R,2S)-2,3-dihydroxy- 1-methylpropyl]oxy}-4-pyrimidinyl]-1-azetidinesulfonamide (prepared for example according to Example 47 in WO2006 / 024823).

[0186] 1. Add compound I MAPI (43.94 g, 100% mass=40.0 g) and acetonitrile (160 mL, 4.0 rel. volume) into container 1 and stir at 20° C.

[0187] 2. Sift the mixture into container 2 and rinse container 1 and the network cable with acetonitrile (20 mL, 0.50 rel vol). Stir and heat to 55°C.

[0188] - Whatman grade 3 filter paper (6 μm pore size, 32 mm circular filter area diameter) was used.

[0189] - The filter paper can be replaced with a new one (if the filter becomes slow with suction).

[0190] - The solution is weighed after filtration and found to be less than the expected mass. It was topped up by adding a small amount of acetonitrile (10 mL, 0.25 rel vol) to correct for apparent evaporation losses. ...

Embodiment 2

[0231] Example 2: Form D - Compound I Anhydrate

[0232] Form A of compound I obtained as described in Example 1 was converted to Form D.

[0233] Form A of Compound 1 was slurried in methanol at 50°C for 6 weeks to afford Form D.

[0234] Form D can also be obtained by slurrying the product of Example 47 in WO2006 / 024823 in methanol at 50°C for 6 weeks.

[0235] Form D has a melting point of 152.7°C (onset) using DSC. Participate image 3 .

[0236] Using 1.5418 on a Thermo ARL X’TRA XRD machine The XRPD pattern of Form D determined by the wavelength is shown in figure 2 are listed in Table 2 below.

[0237] Table 2

[0238]

[0239]

[0240] Using 1.5418 on a Bruker D4XRD machine The XRPD pattern of the form obtained by Example 1, determined at the wavelength of , is listed in Table 2A below.

[0241] Table 2A

[0242] D value

[0243] d=4.049

Embodiment 3

[0245] Example 3: Form D - Compound I Anhydrate

[0246] Using antisolvent crystallization, the D variant can be generated using ethanol as solvent and water as antisolvent.

[0247] Prepare an 80% saturated solution of the compound in ethanol, for example by dissolving 1 rel weight of the compound in 83 rel volumes of ethanol (equivalent to 12 mg AZD5069 in 1 mL ethanol) at a temperature of 25 °C. The solutions can be prepared from Form A crystalline material or from amorphous material. To this solution was added 166 rel. volumes of water (ie, twice the volume of water as ethanol), either continuously over a period of time or in several portions. Upon addition of water the compound crystallizes as the D modification and can be isolated by filtration from the slurry.

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Abstract

There is provided crystalline forms of N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-{[(1R,2S)-2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]1-azetidinesulfon-amide anhydrate. Such compounds / forms may be useful in the treatment of a disease / condition in which modulation of chemokine receptor activity is beneficial.

Description

technical field [0001] The present invention relates to new solid state forms of drugs, pharmaceutical compositions comprising them and methods for obtaining them. Background technique [0002] In formulating pharmaceutical compositions, it is desirable that the drug product be in a form that can be easily handled and processed. This is important not only from the point of view of obtaining a commercially viable manufacturing process, but also from the point of view of the subsequent manufacture of pharmaceutical formulations comprising the active compound. [0003] The chemical stability, solid state stability and "shelf life" of the active ingredient are also very important factors. Drug products, as well as compositions containing them, should be capable of efficient storage without exhibiting significant changes in the physicochemical properties of the active ingredient, such as its chemical composition, density, hygroscopicity and solubility. [0004] Furthermore, it ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12A61K31/506
CPCC07D403/12A61K31/506A61K45/06A61P1/00A61P1/04A61P11/00A61P11/06A61P11/08A61P17/06A61P19/00A61P19/02A61P19/10A61P29/00A61P35/00A61P37/00A61P37/08A61P43/00C07D403/10
Inventor B.A.I.古尔伯格P.T.拉森J.P.斯通豪斯
Owner ASTRAZENECA AB
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