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Crystalline forms of 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide salts

IP.com Disclosure Number: IPCOM000201702D
Publication Date: 2010-Nov-18
Document File: 8 page(s) / 94K

Publishing Venue

The IP.com Prior Art Database

Abstract

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Crystalline forms of 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide salts

   4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3- pyridinyl)-2-pyrimidinyl]amino]-benzamide (referred to as "NLT") of the following formula:

N

C

H

3

N

F3C

NH

NH

N

O

N

N

H

3

C

is a tyrosine kinase inhibitor, used in the treatment of drug-resistant chronic myelogenous leukemia (CML).

  Crystalline forms NLT hydrochloride and NLT fumarate salts were found and are described below. Also described a process for preparing crystalline NLT-HCl form T19.

Crystalline NLT HCl form T20

The crystalline form can be characterized by a powder XRD pattern having peaks at 5.3,
7.0, 14.4, 20.1 and 21.1 degrees two theta ± 0.2 degrees two theta a powder XRD pattern substantially as depicted in Figure 1, a powder XRD pattern substantially as depicted in Figure 2, or any combination thereof.


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Fig. 1 shows a PXRD pattern of crystalline NLT HCl form T20 (prepared according to example 1

5000

4000

3000

CPS

2000

1000

0

2.0 6.0 10.0 14.0 18.0 22.0 26.0 30.0 34.0 38.0

2-Theta Scale

Fig. 2 shows a PXRD pattern of crystalline NLT HCl form T20 (prepared according to example 3)

3000

2000

CPS

1000

0

2.0 6.0 10.0 14.0 18.0 22.0 26.0 30.0 34.0 38.0

2-Theta Scale


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  NLT HCl Form T20 may be further characterized by data selected from the group consisting of: an x-ray powder diffraction pattern having additional peaks at about 9.1, 10.9,
19.1, 22.5 and 25.0 degrees two theta ± 0.2 degrees two theta; FT-IR spectrum having peaks at about 745, 803, 998, 1124, 1352, 1378, 1462 and 1525 cm-1 ± 2 cm-1; FT-IR spectrum having peaks at about 749, 798, 869, 969, 1378, 1399, 1455 and 1583 cm-1 ± 2 cm-1; and combinations thereof. When form T20 is characterized by FT-IR spectrum having peaks at about 745, 803, 998, 1124, 1352, 1378, 1462 and 1525 cm-1 ± 2 cm-1, form T20 may be further characterized by FT-IR spectrum substantially as depicted in Figure 3. When form T20 is characterized by FT-IR spectrum having peaks at about 749, 798, 869, 969, 1378, 1399, 1455 and 1583 cm-1 ± 2 cm-1, form T20 may be further characterized by FT-IR spectrum substantially as depicted in Figure 4.

Fig. 3 shows a FT-IR spectrum of crystalline NLT HCl form T20 (prepared according to example 1)

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Fig. 4 shows a FT-IR spectrum of crystalline NLT HCl form T20 (prepared according to example 3)

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Crystalline NLT fumarate

The crystalline form can be characterized by a powder XRD pattern having peaks at 4.8,
8.9, 16.2, 18.5 and 19.7 degrees two theta ± 0.2 degrees two theta, a powder XRD pattern substantially as depicted in Figure 5, a powder XRD pattern substantially as depicted in Figure 6, or a combination thereof.


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Fig. 5 shows a PXRD pattern of crystalline NLT fumarate (...