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New polymorphs of N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate

IP.com Disclosure Number: IPCOM000204533D
Publication Date: 2011-Mar-02
Document File: 6 page(s) / 117K

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The IP.com Prior Art Database

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  New polymorphs of N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate

N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate, has the following chemical structure:

O

It is currently marketed in the United States as an approved drug for use in patients with advanced metastatic breast cancer.

Provided are novel solid crystalline forms of N-[3-chloro-4-[(3- fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate referred to as Forms A, B, C, D, E, and F.

Preparation of Form A

Solid N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate (1g) was suspended in trifluoroethanol (TFE) (5V), and the resulting suspension was heated to reflux (78°C) with stirring over 0.5h. The resulting solution was then cooled to 25°C over 1h to produce a yellow suspension. The suspension was stirred at 25°C for an additional 1h, and then it was filtered. The product was analyzed by X-ray powder diffraction (as shown in the following figure) and its XRD peaks are represented by the characteristic XRPD pattern: Main XRD peaks of Form A prepared according to the method above are:

S

O

O

O

Cl

F

N

H

N

H

N

x 2

N

HO3S CH3


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4.4°, 8.2°, 9.6°, 13.0°, 14.2°, 14.9°, 15.5°, 16.2°, 16.9°, 17.9°, 18.5°, 19.1°, 20.0°, 20.8°,
21.9°, 22.9°, 23.4°, 24.3°, 25.0°, and 30.4º ± 0.2º two theta.

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Preparation of Form B

Solid N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine ditosylate (1g) was suspended in TFE (5V). The resulting suspension was heated to reflux (78°C) with stirring over 0.5h. The resulting solution was then cooled to 25°C over 1h to produce a yellow suspension. The suspension was stirred for an additional 1h at 25°C, and then it was filtered. The product was analyzed by X-ray powder diffraction (as shown in the following figure) and its XRD peaks are represented by the characteristic XRPD pattern: Main XRD peaks of Form B prepared according to the method above are: 4.6°, 8.3°, 8.6°,
9.3°, 9.7°, 12.0°, 13.3°, 13.8°, 14.8°, 15.6°, 15.9°, 16.1°, 16.8°, 17.4°, 18.7°, 19.6°, 20.7°,
21.2°, 21.7°, 22.0°, 22.5°, 23.1°, 25.1°, 26.9°, 27.5° and 37.7° ± 0.2º two theta.


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Preparation of Form C

Solid N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine (1g) was suspended in TFE (5V). The resulting suspension was heated to 40°C to dissolve. To the solution was added p-toluenesulfonic acid (PTSA) (0.72g, 2eq). The resulting suspension was stirred over 0.5h. Then it was cooled to 25°C, an...